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Background: Acute aortic regurgitation is life-threatening with few nonsurgical options for immediate stabilization. We propose Trans-Aortic Balloon to Ease Regurgitation Applying Counter-Pulsation (TABERNACL), a simple, on-table temporary valve using commercially available equipment to temporize acute severe aortic regurgitation., Methods: We hypothesize that an appropriately sized commercial balloon dilatation catheter-straddling the aortic annulus and connected to a counterpulsation console-can serve as a temporizing valve to restore hemodynamic stability in acute aortic regurgitation. We performed benchtop testing of valvuloplasty, angioplasty, and sizing balloons as counterpulsation balloons. TABERNACL was assessed in vivo in a porcine model of acute aortic regurgitation (n=8). We also tested a static undersized, continuously inflated transvalvular balloon as a spacer intended physically to obstruct the regurgitant orifice., Results: Benchtop testing identified that Tyshak II and PTS sizing (NuMed Braun) balloon catheters performed adequately as temporary valves (ie, complete inflation and deflation with each cycle) and resisted fatigue, in contrast to others. When TABERNACL was used in the acute severe regurgitation animals, there was immediate hemodynamic improvement, with a significant 35% increase in diastolic aortic pressure by 16 mm Hg ([95% CI, 7-25] P =0.0056), 34% reduction in left ventricular end-diastolic pressure by -7 mm Hg ([95% CI, -10 to -5] P =0.0006), improvement in the aortic diastolic index by 0.28 ([95% CI, 0.18-0.39] P =0.0009), and reversal of electrocardiographic myocardial ischemia. As an alternative, static balloon inflation across the aortic valve stabilized regurgitation hemodynamics at the expense of a new aortic gradient and caused excessive ectopy from balloon movement in the left ventricular outflow tract., Conclusions: TABERNACL improves hemodynamics and reduces coronary ischemia by electrocardiography in animals with acute severe aortic regurgitation. TABERNACL valves obstruct the diastolic regurgitant orifice without systolic obstruction. This may prove a lifesaving bridge to definitive valve replacement therapy., Competing Interests: Disclosures Dr Rogers reports consulting from Edwards Lifesciences, Medtronic, Boston Scientific, and Transmural Systems; is on the advisory board at Medtronic and Boston Scientific; reports equity interest in Transmural Systems; and reports intellectual property (coinventor on patents), assigned to the National Institutes of Health (NIH), for transcatheter electrosurgery devices. Dr Khan reports educational grants from Abbott, Boston Scientific, Edwards Lifesciences, and Philips; is a proctor at Edwards Lifesciences and Medtronic; reports equity interest in Transmural Systems; and reports intellectual property (coinventor on patents), assigned to NIH, for transcatheter electrosurgery devices. The other authors report no conflicts.

Acute high-output heart failure (HOHF) with pulmonary hypertension and liver injury caused by amlodipine poisoning is very rare. We report a 52-year-old woman who suffered from severe shock after an overdose of amlodipine. Hemodynamic monitoring showed that while her left ventricular systolic function and cardiac output were elevated, her systemic vascular resistance decreased significantly. At the same time, the size of her right heart, her central venous pressure, and the oxygen saturation of her central venous circulation all increased abnormally. The patient's circulatory function and right ventricular dysfunction gradually improved after large doses of vasopressors and detoxification measures. However, her bilirubin and transaminase levels increased significantly on hospital day 6, with a CT scan showing patchy, low-density areas in her liver along with ascites. After liver protective treatment and plasma exchange, the patient's liver function gradually recovered. A CT scan 4 months later showed all her liver abnormalities, including ascites, had resolved. The common etiologies of HOHF were excluded in this case, and significantly reduced systemic vascular resistance caused by amlodipine overdose was thought to be the primary pathophysiological basis of HOHF. The significant increase in venous return and pulmonary blood flow is considered to be the main mechanism of right ventricular dysfunction and pulmonary hypertension. Hypoxic hepatitis caused by a combination of hepatic congestion and distributive shock may be the most important factors causing liver injury in this patient. Whether amlodipine has other mechanisms leading to HOHF and pulmonary hypertension needs to be further studied. Considering the significant increase of right heart preload, aggressive fluid resuscitation should be done very cautiously in patients with HOHF and shock secondary to amlodipine overdose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the quantitative measurements obtained for vessel density (VD) of the optic nerve head, macula, peripapillary retinal nerve fibre layer (p-RNFL) and total retinal thicknesses (Trt) by optical coherence tomography angiography (OCT-A) and the choroidal vascular structure using an image binarization method in children with epilepsy using three different antiepileptic drugs (AEDs) and to compare these measurements with healthy participants., Methods: This observational, cross-sectional study included 124 patients divided into 4 groups: Group-1: patients receiving carbamazepine(n = 30), group-2: patients receiving levetiracetam (n = 31), group-3: patients receiving valproic acid (n = 32), and group 4: healthy controls (n = 31).A fully automated microstructural analysis of the VD of the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and the choriocapillaris (CC) layers and radial peripapillary capillary, and Trt, p-RNFL thickness were analyzed by using OCT-A. Enhanced depth imaging (EDI)-OCT scans of the macula were obtained and the images were binarized using the ImageJ software., Results: The mean age, gender distribution and the duration of epilepsy were similar in all groups. Evaluation of the p-RNFL thickness and perifoveal Trt between the groups showed a statistically significant difference in all quadrants.The p-RNFL thickness was lower in patients receiving carbamazepine and valproic acid. The lowest values of the luminal area and choroidal vascular index (CVI) were found in patients receiving valproic acid; comparison with matched healthy controls showed statistically significant differences., Conclusion: Valproic acid and carbamazepine are associated with thinning of the p-RNFL in epilepsy patients, but the macular and radial peripapillary VD were not affected.However, a reduction of choroidal vascular blood flow was found in epilepsy patients taking valproic acid., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Smoke from traditional cigarettes and e-cigarette aerosols have distinct chemical compositions that may impact blood pressure (BP) and heart rate (HR) differently., Aims: This study compared the impact of nicotine-containing e-cigarettes (EC+) versus nicotine-free (EC-) on BP, HR and endothelial markers, and assessed if EC+ posed fewer risks than tobacco cigarettes (TC)., Methods: Electronic databases were searched from inception until November 2023 for studies reporting changes in systolic and diastolic BP (SBP, DBP) and HR and endothelial parameters before and after the use of EC+, EC- and TC. Data were analyzed using weighted mean differences (WMDs) and 95% confidence intervals (CIs)., Results: Fifteen studies (n = 752) were included in our meta-analysis. We demonstrate that EC+ significantly increased systolic BP (WMD = 3.41, 95% CI [0.1,6.73], p = 0.04], diastolic BP (WMD = 3.42, 95% CI [1.75, 5.09]; p < 0.01], and HR (WMD = 5.36 BPM, 95% CI [1.87, 8.85]; p < 0.01) compared to EC-. However, EC+ was observed to cause less detrimental effect on SBP (WMD = - 4.72 mmHg, 95% CI [- 6.58, - 2.86], p < 0.01), and HR (WMD = - 3.11 BPM, 95% CI [- 4.54, - 1.68]; p < 0.01) as compared to TC with no difference on DBP (WMD = - 1.14 mmHg, 95% CI [- 2.38, 0.1]; p = 0.07). EC+ also led to greater deterioration of endothelial parameters as compared to EC- but to a lesser degree as compared to TC., Conclusion: EC+ shows greater impairment in hemodynamic and endothelial parameters than EC- but less than TC. Additional studies are needed to evaluate prolonged effects of EC use., (© 2024. Italian Society of Hypertension.)

The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.

Introduction: during laparoscopic surgery, carbon dioxide (CO 2 ) insufflation to create pneumoperitoneum increases blood pressure, heart rate and systemic vascular resistance. The purpose of our study was to investigate the efficacy of magnesium sulfate in preventing adverse hemodynamic reactions associated with pneumoperitoneum in patients undergoing laparoscopic cholecystectomy., Methods: we conducted a prospective, randomized, double-blind, controlled clinical study of patients scheduled for laparoscopic cholecystectomy and divided into two equal groups: the Mg 2+ group received slow intravenous magnesium sulfate 50 mg/kg injection prior to pneumoperitoneum insufflation while the S group received the same volume of 0.9 % saline. Our primary endpoint was intraoperative changes in systolic blood pressure (SBP) related to pneumoperitoneum, in particular at 1 minute after insufflation. The secondary endpoints were the haemodynamic effects of pneumoperitoneum in terms of systolic blood pressure (SP), diastolic blood pressure (DP), mean arterial pressure (MAP) and heart rate (HR) from 2 minutes after insufflation to extubation and postoperatively, and the presence of possible adverse reactions related to the administration of magnesium sulphate., Results: we included 70 patients divided into two groups of 35. SP was significantly higher in the S group at insufflation (T0), 3 min, 4 min and 5 min post-operative, and at 60 min after surgery. HR was significantly higher in patients in the S group compared to the Mg 2+ group at 7 min and 8 min after insufflation. No significant differences in DP and MAP measurements were observed between the 2 groups. No adverse reactions related to magnesium administration were reported., Conclusion: magnesium sulfate administered prior to pneumoperitoneum insufflation provided improved intraoperative hemodynamic stability during laparoscopic surgery., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts., (Copyright: Imen Zouche et al.)

Objective. Dopaminergic treatment is effective for Parkinson's disease (PD). Nevertheless, the conventional treatment assessment mainly focuses on human-administered behavior examination while the underlying functional improvements have not been well explored. This paper aims to investigate brain functional variations of PD patients after dopaminergic therapy. Approach. This paper proposed a dynamic brain network decomposition method and discovered brain hemodynamic sub-networks that well characterized the efficacy of dopaminergic treatment in PD. Firstly, a clinical walking procedure with functional near-infrared spectroscopy was developed, and brain activations during the procedure from fifty PD patients under the OFF and ON states (without and with dopaminergic medication) were captured. Then, dynamic brain networks were constructed with sliding-window analysis of phase lag index and integrated time-varying functional networks across all patients. Afterwards, an aggregated network decomposition algorithm was formulated based on aggregated effectiveness optimization of functional networks in spanning network topology and cross-validation network variations, and utilized to unveil effective brain hemodynamic sub-networks for PD patients. Further, dynamic sub-network features were constructed to characterize the brain flexibility and dynamics according to the temporal switching and activation variations of discovered sub-networks, and their correlations with differential treatment-induced gait alterations were analyzed. Results. The results demonstrated that PD patients exhibited significantly enhanced flexibility after dopaminergic therapy within a sub-network related to the improvement of motor functions. Other sub-networks were significantly correlated with trunk-related axial symptoms and exhibited no significant treatment-induced dynamic interactions. Significance. The proposed method promises a quantified and objective approach for dopaminergic treatment evaluation. Moreover, the findings suggest that the gait of PD patients comprises distinct motor domains, and the corresponding neural controls are selectively responsive to dopaminergic treatment., (© 2024 IOP Publishing Ltd.)

Objective: In our study, we aimed to compare the effect of standard rapid sequence intubation protocol and the application of rocuronium priming technique on the procedure time and hemodynamic profile., Methods: Patients who applied to the emergency department and needed rapid sequence intubation were included in our study, which we conducted with a randomized controlled design. Randomization in the study was made according to the order of arrival of the cases. Rapid sequence intubation was performed in the standard group. In the priming group, 10% of the rocuronium dose was administered approximately 3 min before the induction agent. Intubation time, amount of drug used, vital signs, and end-tidal CO2 level before and after intubation used to confirm intubation were recorded., Results: A total of 52 patients were included in the study, of which 26 patients were included in the standard group and 26 patients in the priming group. While intubation time was 121.2±21.9 s in the standard group, it was calculated as 68.4±11.6 s in the priming group (p<0.001). While the mean arterial pressure was 58.3±26.6 mmHg in the standard group after intubation, it was 80.6±21.1 mmHg in the priming group (p=0.002)., Conclusion: It was observed that priming with rocuronium shortened the intubation time and preserved the hemodynamic profile better., Clinical Trial Registration Number: NCT05343702.

Few studies have investigated the hemodynamic mechanism whereby primary hyperaldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. Recently, we investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we found that aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. In addition, we validated mathematical models of human integrative physiology, derived from Guyton's classic 1972 model - Quantitative Cardiovascular Physiology-2005 and HumMod-3.0.4. Neither model accurately predicted the usual changes in sodium balance, CO, and SVR that normally occur in response to clinically realistic increases in salt intake. These results demonstrate significant limitations with the hypotheses inherent in the Guyton models. Together these findings challenge the traditional view of the hemodynamic mechanisms that cause salt-sensitive hypertension in primary aldosteronism. Key words: Aldosterone, Blood pressure, Salt, Sodium, Rat.

Objectives: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA)., Methods: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis., Results: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA ( P <0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA ( P <0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% ( P <0.05)., Conclusions: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Objective: Breast cancer, a prevalent global malignancy in women, necessitates a comprehensive treatment approach, with surgery playing a crucial role. Severe acute pain is common post-radical breast cancer surgery, emphasizing the significance of hemodynamic stability and postoperative pain control for optimal outcomes. This study evaluates the impact of ultrasound-guided erector spinae plane block (ESPB) on these parameters in ASA scores 1-2 patients undergoing modified radical breast cancer surgery with general anesthesia., Patients and Methods: Forty-eight patients were divided into two groups: a general anesthesia group, with erector spinae plane block (GA+ESPB), and a control group receiving only general anesthesia (GA). Hemodynamic parameters were continuously monitored, and postoperative pain was assessed using the visual analog scale (VAS) at various time points., Results: Ultrasound-guided ESPB effectively maintained hemodynamic stability and reduced postoperative pain in breast cancer surgery patients. Statistically significant differences were observed in heart rate, systolic and diastolic blood pressure, and mean arterial pressure between the GA and GA+ESPB groups at multiple time points (p < 0.05). VAS scores showed a significant interaction time*group (p < 0.001), with consistent differences between the groups at all time points (p ≤ 0.001)., Conclusions: Ultrasound-guided ESPB application proved effective in preserving hemodynamic stability and managing postoperative pain in modified radical breast cancer surgery. The technique demonstrates promise in minimizing complications related to hemodynamic variations and postoperative pain, contributing to a comprehensive approach to breast cancer surgical treatment.

The purpose of the study is to optimize monitoring and personalize antihypertensive therapy in patients with severe ischemic cerebral stroke (ICS). We examined 37 patients with ICS, average age 74,1±1,3 years, who received treatment in intensive care wards of the stroke department with general neurology beds of the Municipal Non-Profit Enterprise "City Hospital № 9" of the Zaporizhzhia City Council. There were 16 men (43,2%), average age 71,9±2,1 years; women - 21 (56,8%), average age 75,8±1.6 years. Personification of antihypertensive therapy for severe ICS was carried out based on the etiology of hypertensive hemodynamic disorders: hyperkinetic type of arterial hypertension (Cardiac index ≥ 3,80 L×min-1×m-2) or hypokinetic type of arterial hypertension (Cardiac index ≤ 2,98 L×min-1×m-2). In patients with severe ICS and hyperkinetic type of arterial hypertension, initial hemodynamic parameters were characterized by Mean arterial pressure (MAP) of 111,4 ± 1,4 mm Hg; Heart rate (HR) of 107,2±1,6 min; Cardiac index (CI) 6,74±0,27 L×min-1×m-2; the Total peripheral vascular resistance (TPVR) is 674±36 dyn×sec-1×cm-5. For the purpose of antihypertensive correction of the hyperkinetic type of arterial hypertension (CI ≥ 3,80 L×min-1×m-2), a solution of Magnesium Sulfate was used intravenously at a dose of 2500-5000 mg×day-1 in combination with Bisoprolol 5-10 mg×day-1 orally. This made it possible to stabilize hemodynamic parameters by the end of intensive therapy within the limits of eukinetic values: MAP 95,2±1,5 mm Hg (p<0,05); HR 81,9±1,5 min (p<0,05); CI 3,60±0,15 L×min-1×m-2 (p<0,05); TPVR is 1079±58 dyn×sec-1×cm-5 (p<0,05). In patients with severe ICS and hypokinetic type of arterial hypertension, initial hemodynamic parameters were characterized by MAP of 117,7±2,8 mm Hg; HR of 76,7±1,5 min; CI 2,74±0,18 L×min-1×m-2; TPVR is 1754±123 dyn×sec-1×cm-5. For the purpose of antihypertensive correction of the hypokinetic type of arterial hypertension (CI≤2,98 L×min-1×m-2), a solution of Ebrantil was used intravenously as a bolus of 1,25-2,5 mg with a further infusion of 5-40 mg×hour-1. This made it possible to stabilize hemodynamic parameters by the end of intensive therapy within the limits of eukinetic values: MAP 92,7 ± 1,7 mm Hg (p<0,05); HR 81,4 ± 0,9 min (p<0,05); CI 3,65±0,16 L×min-1×m-2 (p<0,05); TPVR is 1036±46 dyn×sec-1×cm-5 (p<0,05).

To investigate the effect of sevoflurane inhalation anesthesia on hemodynamics in children undergoing lower limb fracture surgery. Between January 2019 and December 2021, 187 kids at our hospital were randomly divided into two distinct categories: the experimental category (95 cases) and the control category (92 cases). Sevoflurane inhalation anesthesia was administered to the experimental cohort whereas Ketamine basic anesthesia was administered to the control cohort. Comparisons were made among the two categories' hemodynamic indices, anesthetic quality, and VAS ratings. When the eyelash reflex vanished, immediately after skin incision, as well as 5 min after skin incision, the SaO2, as well as MAP in the experimental group, were higher than those in the control category, while HR, SBP, as well as DBP were less than those in the control category. These variations were statistically noteworthy (P < .05). The onset of the experimental group's sensory blocks and the awakening of patients was faster than the control category, and the variations were of statistical importance (P < .05). At 24 hours, 48 hours, and 72 hours, the VAS score in the experimental category was substantially distinct from that in the control category (P < .05). In addition to lowering postoperative discomfort and stabilizing hemodynamics, sevoflurane inhalation anesthesia helps speed up the onset and recovery of anesthesia block in children having lower extremity fracture surgery.

Background: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation., Objective: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl)., Methods: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05., Results: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026)., Conclusion: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

Background: Current neonatal resuscitation guidelines recommend epinephrine for cardiac arrest. Vasopressin might be an alternative during asphyxial cardiac arrest. We aimed to compare vasopressin and epinephrine on incidence and time to return of spontaneous circulation (ROSC) in asphyxiated newborn piglets., Design/methods: Newborn piglets (n = 8/group) were anesthetized, intubated, instrumented, and exposed to 30 min of normocapnic hypoxia, followed by asphyxia and asystolic cardiac arrest. Piglets were randomized to 0.2, 0.4, or 0.8IU/kg vasopressin, or 0.02 mg/kg epinephrine. Hemodynamic parameters were continuously measured., Results: Median (IQR) time to ROSC was 172(103-418)s, 157(100-413)s, 122(93-289)s, and 276(117-480)s for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine groups, respectively (p = 0.59). The number of piglets that achieved ROSC was 6(75%), 6(75%), 7(88%), and 5(63%) for 0.2, 0.4, 0.8IU/kg vasopressin, and 0.02 mg/kg epinephrine, respectively (p = 0.94). The epinephrine group had a 60% (3/5) rate of post-ROSC survival compared to 83% (5/6), 83% (5/6), and 57% (4/7) in the 0.2, 0.4, and 0.8IU/kg vasopressin groups, respectively (p = 0.61)., Conclusion: Time to and incidence of ROSC were not different between all vasopressin dosages and epinephrine. However, non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin groups warrant further investigation., Impact: Time to and incidence of ROSC were not statistically different between all vasopressin dosages and epinephrine. Non-significantly lower time to ROSC and higher post-ROSC survival in vasopressin-treated piglets. Overall poorer hemodynamic recovery following ROSC in epinephrine piglets compared to vasopressin groups. Human neonatal clinical trials examining the efficacy of vasopressin during asphyxial cardiac arrest will begin recruitment soon., (© 2023. The Author(s).)

Background: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy., Objectives: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery., Methods: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events., Results: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively., Conclusions: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Purpose: The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support., Methods: We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock., Results: The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison., Conclusion: The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this., Competing Interests: Declaration of Competing Interest The following authors report no conflict of interest: CL, CC, NA, LR. The following authors received funding by Spero Therapeutics-provided unrestricted research grant via its Investigator Initiated Research Program: BF, MR, GS. GS reports participating in an advisory board meeting for Hema Biologics in 2022 regarding blood factor products. CB reports grant funding from Alexion/Astra Zeneca Rare Disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We studied the dynamics of the main hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with visceral obesity and chemically induced colitis (CIC) against the background of probiotic therapy. Systolic BP, HR, and body temperature were recorded over 36 days using a wireless telemetry system. During 8 days (3 days before CIC induction and until the end of the experiment) the animals were intragastrically administered a probiotic based on Lactobacillus delbrueckii D5 strain. At baseline, systolic BP was significantly higher in the SHR group, while HR and body temperature did not differ in SHR and WKY rats. On day 8 after CIC induction, systolic BP, HR, and body temperature in SHR were significantly increased in comparison with the initial values. In the group of WKY rats, all indices at the end of the experiment remained at the initial levels. Probiotic therapy in SHR, in contrast to WKY rats, did not lead to normalization of body temperature and hemodynamic disorders resulting from CIC., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [ CI ]: 1.24 - 3.58; P =0.006) and bradycardia (OR: 2.48; 95% CI : 1.57 - 3.93; P =0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95% CI : 1.06 - 3.79; P =0.03) and bradycardia (OR: 2.28; 95% CI : 1.42 - 3.66; P =0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95% CI : 1.24 - 6.82; P =0.01) and bradycardia (OR: 2.66; 95% CI : 1.53 - 4.61; P =0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95% CI : 1.41 - 17.37; P =0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95% CI : 1.05 - 6.32; P =0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95% CI : 1.06 - 6.15; P =0.04) and severe (OR: 2.45; 95% CI : 1.43 - 4.20; P =0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95% CI : -109.04 - -56.90; P <0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

Objective: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine., Study Design: Prospective, randomized, blinded, clinical trial., Animals: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy., Methods: Each dog received dexmedetomidine (5 μg kg -1 ) and methadone (0.2 mg kg -1 ) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO 2 ) was also recorded. Prior to surgery, animals received either 0.1 mg kg -1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests., Results: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO 2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01)., Conclusions and Clinical Relevance: Labetalol at a dose of 0.1 mg kg -1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

Importance: At present, there is no consensus on the concentration of epinephrine/physiological saline for subcutaneous injection into external auditory canal (EAC) under general anesthesia in otoendoscopic surgery. A randomized controlled trial (RCT) research is needed to provide reference, as this concentration can provide satisfactory surgical field clarity while maintaining patients' hemodynamic stability., Objective: Comparison of the effect of subcutaneous injection of different concentrations of epinephrine/physiological saline into EAC under general anesthesia in otoendoscopic surgery on surgical field clarity and hemodynamics., Design: This double-blind, RCT study was about the effect of topical epinephrine injection in otoendoscopic surgery., Setting: This study was conducted at a single institution., Participants: This study included 168 patients conformed to the inclusion criteria., Intervention: Patients were randomized to receive different concentrations of epinephrine/physiological saline injection (1:5000, 1:10,000, 1:20,000, or 1:40,000) into the junction of bone and cartilage at posterior wall of EAC during surgery., Main Outcome Measures: Surgical field clarity was assessed with surgical field clarity grading scale and tympanic membrane flap flipping time. Hemodynamic changes were monitored by clinical parameters of blood pressure, heart rate, and ST segment of ECG., Results: There were no statistically-significant differences in surgical field clarity grade ( P  = .577) and tympanic membrane flap flipping time ( P  = .490) among 4 concentration groups. Epinephrine injection did cause an increase in hemodynamic parameters when compared with baseline ( P  < .05). Compared with the relatively-lower concentration groups (1:20,000 and 1:40,000), the relatively-higher concentration groups (1:5000 and 1:10,000) had more significant and long-lasting effect until 30 minutes after injection., Conclusions and Relevance: Four concentration groups of topical epinephrine injection in otoendoscopic surgery have the same effect on surgical field clarity. For the stability of patients' hemodynamics, we would prefer to recommend the use of concentrations with minimal impact on hemodynamics, ranging from 1:20,000 to 1:40,000., Trial Registration: Clinical Trial Registry-China: ChiCTRI1800016647., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute heart failure, advanced cardiac failure, cardiac surgery, and sepsis are conditions that require simultaneous treatment to stimulate contractility and/or reduce systemic vascular resistance, with levosimendan and milrinone being treatment options. This research's aim is to review the current indications and evidence for these medications across various scenarios. Evidence suggests that levosimendan is a non-inferior alternative to dobutamine and superior to milrinone in treating low cardiac output syndrome following cardiac surgery. In cases of septic shock, levosimendan has been linked to lower mortality rates compared to placebo, while milrinone's efficacy remains inconclusive. Furthermore, postoperative patients undergoing correction for congenital heart disease have shown reduced mechanical ventilation time and intensive care unit stays when treated with levosimendan, although differences exist between the populations assigned to each intervention. In conclusion, levosimendan, compared to milrinone, appears to offer better hemodynamic favorability in patients undergoing cardiac surgery. However, additional research is necessary to further understand its impact on hemodynamic outcomes, mortality, intensive care unit, and hospital stays in patients with cardiogenic shock of both ischemic and non-ischemic etiologies, as well as septic shock., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Dental extraction or tooth extraction is a common clinical radical treatment surgery., Objective: To explore the efficacy and safety of remimazolam in tooth extraction surgery in a randomized, single-blind, multi-center clinical trial., Method: Patients who underwent tooth extraction surgery at Jinan Stomatological Hospital from April 2022 to March 2023 were selected as the research subjects, and they were divided into a control group and an observation group using the random arrangement table method. The patients in the control group were anesthetized with midazolam, and the patients in the observation group were anesthetized with remimazolam. Collect the general demographic data of the patients, use the propensity score matching method (PSM) to balance the baseline data of the two groups, and use t-test, chi-square test, and analysis of variance to compare the hemodynamics, anesthesia maintenance period indicators, and alertness/Sedation scores and occurrence of adverse reactions., Result: PSM matching was performed according to a 1:1 ratio, and 40 patients were included in the observation and control groups. There was no statistical significance in the baseline data of the two groups. Compared with T0, the hemodynamic indexes of both groups of patients increased at T1, T2, T3, T4, and T5 (P< 0.05), but the indexes at T0 and T2 were the same. The same (P> 0.05), and the indicators of the observation group at T1, T3, T4, and T5 were higher than those of the control group (P< 0.05); the administration time of the two groups of patients was the same (P> 0.05), but the observation group The recovery time and onset of effect were shorter than those in the control group (P< 0.05); at T0, the clinical behavior scores of the two groups of patients were the same (P> 0.05), and at T1, the scores of the observation group were lower than those of the control group (P< 0.05); at T0 and T1, the alertness/sedation scores of the patients in the observation group were lower than those in the control group, but at T2, the scores of the patients in the observation group were higher than those in the control group (P< 0.05); the total clinical adverse reactions of the patients in the observation group were The incidence rate (5.00%) was lower than that of the control group (30.00%) (P< 0.05)., Conclusion: The use of remimazolam during tooth extraction can stabilize the patient's hemodynamics, shorten the recovery and onset time, stabilize the patient's behavior, have an excellent soothing effect, have fewer adverse reactions, and be safer, so it is worthy of use.

Introduction: Nicotinamide adenine dinucleotide (NAD + ) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD + may be cardioprotective. However, whether the protective effect exerted by NAD + in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week, following which the animals were treated for 4 weeks with low, medium, and high doses of NAD + and LCZ696., Methods: Cardiac function, hemodynamics, and biomarkers were evaluated during the treatment period. Heart weight, myocardial fibrosis, and MI rate were measured eventually., Results: Compared with the HF groups, groups treated with LCZ696 and different doses of NAD + showed increased ejection fractions, fractional shortening, cardiac output, and stroke volume and decreased end-systolic volume, end-systolic dimension, creatine kinase, and lactic dehydrogenase. LV blood pressure was lower in the HF group than in the control group, but this decrease was significantly greater in the medium and high NAD + dose groups., Conclusion: The ratios of heart weight indexes, fibrotic areas, and MI rates in the CZ696 and medium and high NAD + dose groups were lower than those in the HF group. Medium and highdose NAD + showed superior positive effects on myocardial hypertrophy, cardiac function, and myocardial fibrosis and reduced the MI rate., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: A novel tool for the evaluation of left ventricular (LV) systo-diastolic function through echo-derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6 month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events., Methods and Results: Eighty-nine consecutive HFrEF patients [70% males, 65 ± 9 years, LV ejection fraction (LVEF) 27 ± 7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N-terminal pro-B-type natriuretic peptide and/or ≥10% LVEF increase over 6 months were considered responders. Patients were followed up for the composite endpoint of HF-related hospitalisation, atrial fibrillation and cardiovascular death. Forty-five (51%) patients were responders. Among baseline variables, only HDF-derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4 ± 1.3 vs. 3.6 ± 1.2; p = 0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10-1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC) = 0.736]. During a 33 month (23-41) median follow-up, a wLVS increase after 6 months (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≥0.5%; AUC = 0.811), stratified prognosis (log-rank p < 0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61-0.95; p < 0.01), after adjusting for clinical and instrumental variables., Conclusions: HDF analysis predicts sacubitril/valsartan response and might optimise decision-making in HFrEF patients., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Study Objective: To determine the 50% and 95% effective doses (ED50 and ED95, respectively), hemodynamic effects, and safety of intranasal dexmedetomidine for preoperative sedation in pediatric patients with congenital heart disease (CHD) with a left-to-right shunt., Design: Double-blind sequential allocation trial., Setting: Pediatric preoperative waiting area., Patients: 86 pediatric patients ASA physical status II-III scheduled for cardiac surgery, aged1-month to 6-years-old with left-to-right type CHD., Interventions: Children were divided into three groups according to age: infants (1 month-1 year), toddlers (1-3 years), and preschoolers (3-6 years). The first patient in all groups received intranasal dexmedetomidine (2 μg/kg), using the up-and-down Dixon method, and the and the next patient's dose was dependent on the previous patient's response., Measurements: Assessment using the Modified Observer's Assessment of Alertness/Sedation Scale and the Mask Acceptance Scale was performed before and every 5 min after treatment. Pulse oxygen saturation and heart rate were recorded at baseline, at 10-min intervals, and after admission to the operating room. Systolic pulmonary artery pressure was measured before anesthesia induction., Main Results: The respective ED 50 (95% confidence interval [CI]) and ED 95 (95% CI) values for preoperative sedation using intranasally administered dexmedetomidine were 3.1 (2.8-3.3) and 3.5 (3.3-4.0) μg/kg for infants; 3.4 (3.2-3.6) and 3.9 (3.7-4.4) μg/kg for toddlers; and 2.4 (2.2-2.6) and 2.9 (2.6-3.3) μg/kg for preschoolers. ED 50 was lower for preschoolers than for toddlers (p < 0.001) and infants (p = 0.044). No obvious difference in ED50 was found between infants and toddlers. There was no significant difference in sedation onset time among the groups, and no adverse events were observed during sedation in all patients., Conclusions: Intranasal dexmedetomidine can be safety used for preoperative sedation in children with CHD and is effective for sedation when dosed appropriately. Trial registrationclinicaltrials.gov (ChiCTR2100047472); registered 20 June 2021., (Copyright © 2022 Elsevier Inc. All rights reserved.)

BACKGROUND Perioperative hemodynamic instability mediated by anaphylaxis is a life-threatening complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to evaluate the effect of clemastine fumarate in this specific patient population. MATERIAL AND METHODS We enrolled 100 participants who met the inclusion criteria and randomly allocated them to the treatment group and the placebo group. Participants in the treatment group and the placebo group were treated separately with an injection of clemastine fumarate and saline, respectively. Plasma histamine concentration and blood pressure were quantified at 5 timepoints during the perioperative period, and differences between the 2 groups were assessed by repeated-measures ANOVA. The postoperative complications and in-hospital mortality also were evaluated. All participants were followed up for 7 days after cardiac surgery. RESULTS Plasma histamine concentrations increased in both groups but were statistically significantly lower in the treatment group during the perioperative period (P=0.007). Diastolic blood pressure (P=0.014) and mean arterial pressure (P=0.024) in the treatment group were significantly higher than in the placebo group during the perioperative period. The coefficients of variation for systolic (13.9±4.2% vs 17.2±4.4%, P<0.01) and diastolic (12.9±4.9% vs 15.3±5.2%, P=0.02) blood pressure were significantly lower in the treatment group compared with the placebo group. CONCLUSIONS Pretreatment with clemastine fumarate restrains the increase in histamine concentration and provides safer hemodynamics in patients undergoing cardiac surgery with CPB.

Adenosine is a local mediator that regulates changes in the cardiovascular system via activation of four G protein-coupled receptors (A 1 , A 2A , A 2B , A 3 ). Here, we have investigated the effect of A 2A and A 2B -selective agonists on vasodilatation in three distinct vascular beds of the rat cardiovascular system. NanoBRET ligand binding studies were used to confirm receptor selectivity. The regional hemodynamic effects of adenosine A 2A and A 2B selective agonists were investigated in conscious rats. Male Sprague-Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes on the renal artery, mesenteric artery, and the descending abdominal aorta. Cardiovascular responses were measured following intravenous infusion (3 min for each dose) of the A 2A -selective agonist CGS 21680 (0.1, 0.3, 1 µg kg -1 min -1 ) or the A 2B -selective agonist BAY 60-6583 (4,13.3, 40 µg kg -1 min -1 ) following predosing with the A 2A -selective antagonist SCH 58261 (0.1 or 1 mg kg -1 min -1 ), the A 2B /A 2A antagonist PSB 1115 (10 mg kg -1 min -1 ) or vehicle. The A 2A -selective agonist CGS 21680 produced a striking increase in heart rate (HR) and hindquarters vascular conductance (VC) that was accompanied by a significant decrease in mean arterial pressure (MAP) in conscious rats. In marked contrast, the A 2B -selective agonist BAY 60-6583 significantly increased HR and VC in the renal and mesenteric vascular beds, but not in the hindquarters. Taken together, these data indicate that A 2A and A 2B receptors are regionally selective in their regulation of vascular tone. These results suggest that the development of A 2B receptor agonists to induce vasodilatation in the kidney may provide a good therapeutic approach for the treatment of acute kidney injury., (© 2022 Federation of American Societies for Experimental Biology.)

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO 2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant β-values >7). Myocardial oxygen consumption had almost no effect on T2 (β-values <0.002); since PvO 2 is influenced by both oxygen consumption and MBF, PvO 2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO 2 and MBV confirmed that PvO 2 had the strongest influence on T2, but MBV became important at high PvO 2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue., (© 2021 John Wiley & Sons, Ltd.)

The EP2 receptor has emerged as a therapeutic target with exacerbating role in disease pathology for a variety of peripheral and central nervous system disorders. We and others have recently demonstrated beneficial effects of EP2 antagonists in preclinical models of neuroinflammation and peripheral inflammation. However, it was earlier reported that mice with global EP2 knockout (KO) display adverse phenotypes on fertility and blood pressure. Other studies indicated that EP2 activation with an agonist has a beneficial effect of healing fractured bone in animal models. These results impeded the development of EP2 antagonists, and EP2 antagonism as therapeutic strategy. To determine whether treatment with EP2 antagonist mimics the adverse phenotypes of the EP2 global KO mouse, we tested two EP2 antagonists TG11-77. HCl and TG6-10-1 in mice and rats while they are on normal or high-salt diet, and by two different administration protocols (acute and chronic). There were no adverse effects of the antagonists on systolic and diastolic blood pressure, heart rate, respiratory function in mice and rats regardless of rodents being on a regular or high salt diet. Furthermore, chronic exposure to TG11-77. HCl produced no adverse effects on blood cell counts, bone-volume and bone-mineral density in mice. Our findings argue against adverse effects on cardiovascular and respiratory systems, blood counts and bone structure in healthy rodents from the use of small molecule reversible antagonists for EP2, in contrast to the genetic ablation model. This study paves the way for advancing therapeutic applications of EP2 antagonists against diseases involving EP2 dysfunction., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The ischemic penumbra is sensitive to alterations in cerebral perfusion. A myriad of drugs are used in acute ischemic stroke (AIS) management, yet their impact on cerebral hemodynamics is poorly understood. As part of the Cerebral Autoregulation Network led INFOMATAS project ( Identifying New Targets for Management and Therapy in Acute Stroke) , this paper reviews some of the most common drugs a patient with AIS will come across and their potential influence on cerebral hemodynamics with a particular focus being on cerebral autoregulation (CA). We first discuss how compounds that promote clot lysis and prevent clot formation could potentially impact cerebral hemodynamics, before focusing on how the different classes of antihypertensive drugs can influence cerebral hemodynamics. We discuss the different properties of each drug and their potential impact on cerebral perfusion and CA. With emerging interest in CA status of AIS patients, either during or soon after treatment when timely reperfusion and salvageable tissue is at its most critical, the properties of these pharmacological agents may be relevant for modelling cerebral perfusion accuracy and for setting individualised treatment strategies.

Inflammation triggers pulmonary vascular remodelling. Ferroptosis, a nonapoptotic form of cell death that is triggered by iron-dependent lipid peroxidation and contributes to the pathogenesis of several inflammation-related diseases, but its role in pulmonary hypertension (PH) has not been studied. We examined endothelial cell ferroptosis in PH and the potential mechanisms. Pulmonary artery endothelial cells (PAECs) and lung tissues from monocrotaline (MCT)-induced PH rats were analysed for ferroptosis markers, including lipid peroxidation, the labile iron pool (LIP) and the protein expression of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and NADPH oxidase-4 (NOX4). The effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on endothelial cell ferroptosis and pulmonary vascular remodelling in MCT-induced rats were studied in vitro and in vivo. Ferroptosis was observed in PAECs from MCT-induced PH rats in vitro and in vivo and was characterized by a decline in cell viability accompanied by increases in the LIP and lipid peroxidation, the downregulation of GPX4 and FTH1 expression and the upregulation of NOX4 expression. High-mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signalling was measured by western blotting. These changes were significantly blocked by Fer-1 administration in vitro and in vivo. These results suggest that Fer-1 plays a role in inhibiting ferroptosis-mediated PAEC loss during the progression of PH. The ferroptosis-induced inflammatory response depended on the activation of HMGB1/TLR4 signalling, which activated the NLRP3 inflammasome in vivo. We are the first to suggest that pulmonary artery endothelial ferroptosis triggers inflammatory responses via the HMGB1/TLR4/NLRP3 inflammasome signalling pathway in MCT-induced rats. Treating PH with a ferroptosis inhibitor and exploring new treatments based on ferroptosis regulation might be promising therapeutic strategies for PH., (© 2022. The Author(s).)

Treprostinil palmitil (TP) is a long-acting inhaled pulmonary vasodilator prodrug of treprostinil (TRE). In this study, TP was delivered by inhalation (treprostinil palmitil inhalation suspension, TPIS) in a rat Sugen 5416 (Su)/hypoxia (Hx) model of pulmonary arterial hypertension (PAH) to evaluate its effects on hemodynamics, pulmonary vascular remodeling, and cardiac performance and histopathology. Male Sprague-Dawley rats received Su (20 mg/kg, s.c), three weeks of Hx (10% O 2 ) and 5 or 10 weeks of normoxia (Nx). TPIS was given during the 5-10 week Nx period after the Su/Hx challenge. Su/Hx increased the mean pulmonary arterial blood pressure (mPAP) and right heart size (Fulton index), reduced cardiac output (CO), stroke volume (SV) and heart rate (HR), and increased the thickness and muscularization of the pulmonary arteries along with obliteration of small pulmonary vessels. In both the 8- and 13-week experiments, TPIS at inhaled doses ranging from 39.6 to 134.1 μg/kg, QD, dose-dependently improved pulmonary vascular hemodynamics, reduced the increase in right heart size, enhanced cardiac performance, and attenuated most of the histological changes induced by the Su/Hx challenge. The PDE5 inhibitor sildenafil, administered at an oral dose of 50 mg/kg, BID for 10 weeks, was not as effective as TPIS. These results in Su/Hx challenged rats demonstrate that inhaled TPIS may have superior effects to oral sildenafil. We speculate that the improvement of the pathobiology in this PAH model induced by TPIS involves effects on pulmonary vascular remodeling due to the local effects of TRE in the lungs., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost., Materials and Methods: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality., Results: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status., Conclusion: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.

Introduction: Alcohol septum ablation (ASA) is a treatment option for hypertrophic obstructive cardiomyopathy (HOCM). We examined the impact of ASA-induced bundle branch block (BBB) on clinical and hemodynamic features., Methods and Results: We retrospectively analysed 98 HOCM patients with regard to ASA-induced BBB. Clinical examination was performed at baseline, early after ASA and at chronic follow-up (FU). ASA reduced left ventricular outflow tract gradient (LVOTG) during chronic FU (69.2 ± 41.6 pre vs. 31.8 ± 30.3 mmHg post ASA; p < 0.05) and interventricular septal diameter (21.7 ± 3.4 pre vs. 18.7 ± 5.0 mm post ASA; p < 0.05). ASA-induced early right BBB (RBBB) until discharge was observed in 44.9% and chronic RBBB at FU in 32.7%. Left BBB (LBBB) occurred in 13.3% early after ASA and in only 4.1% at chronic FU. Chronic RBBB was associated with more pronounced exercise-induced LVOTG reduction (102.1 ± 55.2 with vs. 73.6 ± 60.0 mmHg without; p < 0.05). 6-min-walk-test (6-MWT) and NYHA class were not affected by RBBB. LBBB had no influence on LVOTG, 6-MWT and symptoms. More ethanol was injected in patients with early RBBB (1.1 ± 0.4 vs. 0.8 ± 0.3 ml without; p < 0.05), who also showed higher mean CK release (827 ± 341 vs. 583 ± 279 U/l without; p < 0.05). Pacemaker implantation during FU was necessary in 11.5% of patients with early RBBB, 3.1% with chronic RBBB, 7.7% with early LBBB and 0% with chronic LBBB (p = n.s. for BBB vs. no BBB)., Conclusion: ASA-induced RBBB is associated with a higher volume of infused ethanol and higher maximum CK release. RBBB does not adversely affect the clinical outcome or need for pacemaker implantation but was associated with higher exercise-induced LVOTG reduction during chronic FU., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Alpha-terpineol (TPN) is one of the major components of the resin obtained from Protium heptaphyllum. This plant has been utilized as medicine by Brazilian indigenous tribes to treat cardiovascular diseases. Scientific reports have shown that the TPN possesses vasorelaxant and antihypertensive effects. This study was conducted to assess the cardioprotective action of TPN against isoproterenol (ISO)-induced cardiotoxicity. Wistar rats were randomly divided into six groups. Rats were orally administered with TPN (25, 50, and 75 mg/kg, respectively) for 15 days, and ISO was administered (85 mg/kg, subcutaneously) on the 14th and 15th days. At the end of the experiment, the hemodynamic, baroreflex test, ECG, biochemical, histological, and morphometric changes were monitored from control and experimental groups, i.e., on the 15th day. ISO-induced myocardial infarcted rats showed an increase in mortality rates, cardiac marker enzymes, tachycardia, hypertrophy, myocardium necrosis, edema, hemorrhagic areas, infiltration of inflammatory cells like lymphocytes, and increased myocardial infarct size. However, pretreatment with TPN significantly inhibited these effects of ISO. The histopathological findings obtained for the myocardium further confirmed the biochemical results. Thus, the present study provides evidence for the efficacy of TPN against ISO-induced myocardial infarction in rats., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Large clinical studies conducted with sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and heart failure with reduced ejection fraction have demonstrated their ability to achieve both cardiac and kidney benefits. Although there is huge evidence on SGLT2i-mediated clinical benefits both in diabetic and non-diabetic patients, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely due to the prompt glycosuric action which is associated with natriuretic effects leading to hemodynamic benefits as well as a reduction in glomerular hyperfiltration and renin-angiotensin-aldosterone system activation. In addition to the renal mechanisms, SGLT2i may play a relevant role in cardiorenal axis protection by improving the cardiomyocyte metabolism, by exerting anti-fibrotic and anti-inflammatory actions, and by increasing cardioprotective adipokine expression. New studies will be needed to better understand the specific molecular mechanisms that mediate the SGLT2i favorable effects in patients suffering diabetes. Our aim is to first discuss about the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardiorenal axis. Furthermore, we update on the most recent clinical trials evaluating the beneficial effects of SGLT2i in treatment of both diabetic and non-diabetic patients suffering heart failure.

Leptomeningeal anastomoses are small distal anastomotic vessels also known as pial collaterals in the brain. These vessels redirect blood flow during an occlusion and are important for stroke treatment and outcome. Pial collaterals have unique hemodynamic forces and experience significantly increased luminal flow and shear stress after the onset of ischemic stroke. However, there is limited knowledge of how pial collaterals respond to flow and shear stress, and whether this response is altered in chronic hypertension. Using an in vitro system, pial collaterals from normotensive and hypertensive rats (n=6-8/group) were isolated and luminal flow was induced with intravascular pressure maintained at 40 mm Hg. Collateral lumen diameter was measured following each flow rate in the absence or presence of pharmacological inhibitors and activators. Collaterals from male and female Wistar rats dilated similarly to increased flow (2 µL/minute: 58.4±18.7% versus 67.9±7.4%; P =0.275), and this response was prevented by inhibition of the transient receptor potential vanilloid type 4 channel, as well as inhibitors of nitric oxide and intermediate-conductance calcium-activated potassium channels, suggesting shear stress-induced activation of this pathway was involved. However, the vasodilation was significantly impaired in hypertensive rats (2 µL/minute: 17.7±7.7%), which was restored by inhibitors of reactive oxygen species and mimicked by angiotensin II. Thus, flow- and shear stress-induced vasodilation of pial collaterals appears to be an important stimulus for increasing collateral flow during large vessel occlusion. Impairment of this response during chronic hypertension may be related to poorly engaged pial collaterals during ischemic stroke in hypertensive subjects.

Background: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model., Methods: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10., Results: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01)., Conclusion: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment., Methods and Analysis: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72 hours of evolution after volume restoration, using norepinephrine at a dose ≥0.2 μg/kg/min and vasopressin at a dose of 0.04 IU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4)., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Majority of patients with hypertension and chronic kidney disease (CKD) undergoing renal denervation (RDN) are maintained on antihypertensive medication. However, RDN may impair compensatory responses to hypotension induced by blood loss. Therefore, continuation of antihypertensive medications in denervated patients may exacerbate hypotensive episodes. This study examined whether antihypertensive medication compromised hemodynamic responses to blood loss in normotensive (control) sheep and in sheep with hypertensive CKD at 30 months after RDN (control-RDN, CKD-RDN) or sham (control-intact, CKD-intact) procedure. CKD-RDN sheep had lower basal blood pressure (BP; ≈9 mm Hg) and higher basal renal blood flow (≈38%) than CKD-intact. Candesartan lowered BP and increased renal blood flow in all groups. 10% loss of blood volume alone caused a modest fall in BP (≈6-8 mm Hg) in all groups but did not affect the recovery of BP. 10% loss of blood volume in the presence of candesartan prolonged the time at trough BP by 9 minutes and attenuated the fall in renal blood flow in the CKD-RDN group compared with CKD-intact. Candesartan in combination with RDN prolonged trough BP and attenuated renal hemodynamic responses to blood loss. To minimize the risk of hypotension-mediated organ damage, patients with RDN maintained on antihypertensive medications may require closer monitoring when undergoing surgery or experiencing traumatic blood loss.

Introduction: Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used for patients with septic shock, and the recommended hemoperfusion period is 2 h. However, it remains unclear whether the optimal duration is 2 h or longer. The purpose of this study was to compare the effects of PMX-DHP between conventional and longer duration of PMX-DHP., Methods: We retrospectively investigated 103 patients with sepsis who underwent PMX-DHP. The demographic data, routine biochemistry, microbiological data, and primary infection site were reviewed in the medical chart. The acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, heart rate, mean arterial pressure (MAP), vasoactive-inotropic score (VIS), and PaO2/FiO2, at baseline and day 3, were compared between the standard group (2 h of PMX-DHP) and the extended group (>2 h of PMX-DHP)., Results: Median MAP was significantly lower and median VIS was significantly higher in the extended group at baseline (p < 0.05, 0.01, respectively) There were no significant differences in APACHE II score, SOFA score, and PaO2/FiO2 at baseline between the 2 groups. The increase of MAP and the decrease in VIS from baseline to day 3 were significantly greater in the extended group (p < 0.01, respectively). In the extended group, increase in PaO2/FiO2 was significantly larger in the patients who underwent ≥8 h duration than that in patients who underwent <8 h duration (p < 0.01). The ventilator-free days, the incidence of continuous renal replacement therapy, and the 28-day mortality were not different between the groups., Discussion/conclusions: Longer duration of PMX-DHP was associated with the improved MAP and decreased volume of vasoactive-inotropic agents compared with the conventional duration. Eight and longer hours duration of PMX-DHP was associated with the improvement in the pulmonary oxygenation. Further studies are needed to confirm the efficacy of longer duration of PMX-DHP in patients with septic shock., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated., Methods: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus., Results: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229)., Conclusions: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Objectives: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure., Design: Randomized blinded study (animal model)., Setting: University animal research facility., Subjects: Twenty-four adult male "New Zealand White" rabbits., Interventions: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period., Measurements and Main Results: Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis., Conclusions: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Purpose: Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke., Methods: Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication., Results: Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (β=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (β=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (β=0.021%/mm Hg [95% CI, 0.005-0.037])., Conclusions: While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.

Abstract: Infusions of levosimendan delivered in ambulatory/outpatient settings have been shown to improve quality of life and reduce hospitalizations in patients with advanced heart failure (HF). The aim of this pilot study was to evaluate the effects of ambulatory infusion of levosimendan on echocardiographic markers of perfusion, congestion, and cardiovascular efficiency. Thirty patients with diagnosed advanced HF underwent ambulatorial infusion of levosimendan at a total dose of 6.25 mg as a part of a repetitive biweekly treatment strategy with the inotrope. Standardized transthoracic echocardiography and Doppler examinations, were performed 1 hour before and 48 hours after completion of ambulatory infusion. At 48 hours after ambulatory infusion of levosimendan, a significant increase in the stroke volume (37.47 ± 12.38 mL/beat vs. 45.47 ± 14.48 mL/beat; P < 0.05) and cardiac output (2.64 ± 0.66 L/min vs. 3.26 ± 0.57 L/min; P < 0.05) occurred. Significant postreductions versus prereductions were also recorded in left atrial pressure (27.37 ± 6.62 mm Hg vs. 22.82 ± 4.17 mm Hg; P < 0.01), mean pulmonary artery pressure (27.69 ± 4.64 mm Hg vs. 23.24 ± 5.32; P < 0.01), and inferior vena cava diameter (23.81 ± 7.63 mm vs. 18.53 ± 4.82 mm; P < 0.01). Significant improvements were noted in the resting cardiac power output (0.46 ± 0.15 watt vs. 0.53 ± 0.22 watt; P < 0.01) and the resting cardiac power index (0.24 ± 0.08 watt/m2 vs. 0.28 ± 0.11 watt/m2; P < 0.01). In outpatients with advanced HF, infusion of levosimendan was associated with hemodynamic responses that may contribute to the clinical benefit previously reported in such patients., Competing Interests: P. Pollesello is a full-time employee of Orion Pharma, where levosimendan was discovered and developed. The remaining authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)