Search

BACKGROUND: To enhance the utility of functional hemodynamic monitoring, the variables systolic slope (dP/dt) and dynamic arterial elastance (Eadyn) are calculated by the Hypotension Prediction Index (HPI) Acumen® Software. This study was designed to characterize the effects of phenylephrine and ephedrine on dP/dt and Eadyn. METHODS: This was a retrospective, non-randomized analysis of data collected during two clinical studies. All patients required intra-operative controlled mechanical ventilation and had an indwelling radial artery catheter connected to an Acumen IQ sensor. Raw arterial pressure waveform data was downloaded from the patient monitor and all hemodynamic measurements were calculated off-line. The anesthetic record was reviewed for bolus administrations of either phenylephrine or ephedrine. Cardiovascular variables prior to drug administration were compared to those following vasopressor administrations. The primary outcome was the difference for dP/dt and Eadyn at baseline compared with the average after the bolus administration. All data sets demonstrated non-normal distributions so statistical analysis of paired and unpaired data followed the Wilcoxon matched pairs signed-rank test or Mann-Whitney U test, respectively. RESULTS: 201 doses of phenylephrine and 100 doses of ephedrine were analyzed. All data sets are reported as median [95% CI]. Mean arterial pressure (MAP) increased from 62 [54,68] to 78 [76,80] mmHg following phenylephrine and from 59 [55,62] to 80 [77,83] mmHg following ephedrine. Stroke volume and cardiac output both increased. Stroke volume variation and pulse pressure variation decreased. Both drugs produced significant increases in dP/dt, from 571 [531, 645] to 767 [733, 811] mmHg/sec for phenylephrine and from 537 [509, 596] to 848 [779, 930] mmHg/sec for ephedrine. No significant changes in Eadyn were observed. CONCLUSION: Bolus administration of phenylephrine or ephedrine increases dP/dt but does not change Eadyn. dP/dt demonstrates potential for predicting the inotropic response to phenylephrine or ephedrine, providing guidance for the most efficacious vasopressor when treating hypotension. TRIAL REGISTRATION: Data was collected from two protocols. The first was deemed to not require written, informed consent by the Institutional Review Board (IRB). The second was IRB-approved (Effect of Diastolic Dysfunction on Dynamic Cardiac Monitors) and registered on ClinicalTrials.gov (NCT04177225).

During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin organization and gene transcription. In other tissues, circadian oscillations in nucleosome occupancy influence clock-controlled gene expression, suggesting a role for the circadian clock in temporal control of histone turnover and coordinated cardiomyocyte gene expression. We sought to elucidate roles for the master circadian transcription factor, Bmal1, in histone turnover, chromatin organization, and myocyte-specific gene expression and cell growth in the neonatal period. Bmal1 knockdown in neonatal rat ventricular myocytes decreased myocyte size, total cellular protein synthesis, and transcription of the fetal hypertrophic gene Nppb after treatment with serum or the α-adrenergic agonist phenylephrine. Depletion of Bmal1 decreased the expression of clock-controlled genes Per2 and Tcap, as well as Sik1, a Bmal1 target upregulated in adult versus embryonic hearts. Bmal1 knockdown impaired Per2 and Sik1 promoter accessibility as measured by micrococcal nuclease-quantitative PCR and impaired histone turnover as measured by metabolic labeling of acid-soluble chromatin fractions. Sik1 knockdown in turn decreased myocyte size, while simultaneously inhibiting natriuretic peptide B transcription and activating Per2 transcription. Linking these changes to chromatin remodeling, depletion of the replication-independent histone variant H3.3a inhibited myocyte hypertrophy and prevented phenylephrine-induced changes in clock-controlled gene transcription. Bmal1 is required for neonatal myocyte growth, replication-independent histone turnover, and chromatin organization at the Sik1 promoter. Sik1 represents a novel clock-controlled gene that coordinates myocyte growth with hypertrophic and clock-controlled gene transcription. Replication-independent histone turnover is required for transcriptional remodeling of clock-controlled genes in cardiac myocytes in response to growth stimuli.

OBJECTIVE: To assess the performance of transpulmonary thermodilution (TPTD) using room-temperature saline (CORT) and waveform-derived continuous CO (CCO) compared with TPTD using iced saline (COICED) as the indicator for measurements of CO in isoflurane-anesthetized dogs. METHODS: 8 Beagles aged 1 to 2 years (7.4 to 11.2 kg) were enrolled in this experimental study from March 21 to 31, 2023. Dogs were anesthetized with 0.01 mg/kg acepromazine, 5 to 6 mg/kg propofol, and isoflurane and were mechanically ventilated. Dogs were instrumented with a central venous catheter and a femoral arterial catheter equipped with a thermistor. The COICED, CORT, and pulse wave-derived CCO values were obtained at baseline, during infusions of phenylephrine and norepinephrine, and during blood withdrawal and replacement. Data were analyzed with a mixed effect model, Bland-Altman plots, and concordance. Percent error was calculated. P < .05 was used for significance. RESULTS: Data were collected from 8 dogs. Significant effects of time and the interaction of time and method were found. Bland-Altman plots showed negligible bias with limits of agreement between -0.35 and 0.25 L/min for CORT versus COICED and -1.23 and 1.15 L/min for CCO versus COICED. Percent errors were 17.7% and 66.6%, respectively. In the 4-quadrant plots, the concordance rate was 95% and 68% for measurements obtained with CORT and for CCO, respectively. CONCLUSIONS: Transpulmonary thermodilution using room temperature saline was accurate and able to track changes in CO. Continuous CO had a large percent error and low tracking ability. CLINICAL RELEVANCE: Transpulmonary thermodilution using room temperature saline is reliable for monitoring CO and obviates the need for iced preparations in clinical scenarios. [ABSTRACT FROM AUTHOR]

Receptors for activated C kinases (RACKs) have been shown to coordinate PKC-mediated hypertrophic signalling in mice. However, little information is available on its participation in embryonic gene expression. This study investigated the involvement of RACK1 in the expression of embryonic genes in a zebrafish (ZF) ex vivo heart culture model by using phenylephrine (PE) or a growth factors cocktail (GFs) as a prohypertrophic/regeneration stimulus. Blebbistatin (BL) inhibition has also been studied for its ability to block the signal transduction actions of some PEs. qRT‒PCR and immunoblot analyses confirmed the upregulation of RACK1 in the PE- and GFs-treated groups. BL administration counteracted PE-induced hypertrophy and downregulated RACK1 expression. Immunohistochemical analyses of the heart revealed the colocalization of RACK1 and embryonic genes, namely, Gata4, Wt1, and Nfat2, under stimulation, whereas these genes were expressed at lower levels in the BL treatment group. Culturing ZF heart cells activated via GFs treatment increased the expression of RACK1. The overexpression of RACK1 induced by the transfection of recombinant RACK1 cDNA in ZF heart cells increased the expression of embryonic genes, especially after one week of GFs treatment. In summary, these results support the involvement of RACK1 in the induction of embryonic genes during cardiac hypertrophy/GFs stimulation in a fish heart model, which can be used as an alternative study model for mammals. [ABSTRACT FROM AUTHOR]

Background: Perioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias. Objective: We aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant. Methods: This single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes. Results: Twenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05). Conclusion and Relevance: Both AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications. [ABSTRACT FROM AUTHOR]

Background & Objectives: Placental perfusion is not autoregulated and is susceptible to effects of spinal anesthesia (SA) induced hypotension. The perfusion index (PI) is a non-invasive marker of peripheral vascular tone, and a higher PI indicates increased risk of hypotension following SA. This study aims to establish preoperative baseline PI in our local population and its correlation with incidence of intraoperative hypotension. Methods: This prospective observational study recruited 35 parturients who underwent elective lower segment cesarean section (LSCS). Preoperatively, baseline heart rate (HR), systolic blood pressure (SBP), mean arterial pressure (MAP) and PI were documented. SA was performed with 8 to 10 mg of injection bupivacaine 0.5% (hyperbaric) at L3--L4 interspace followed by co-loading with 1 L Hartmann solution. Hypotension was defined as SBP less than 80% of baseline or less than 90 mmHg. A bolus of phenylephrine 50 µg was given as rescue medication to treat the hypotension. Intraoperatively, degree of decrease in SBP, MAP and HR, as well as the amount of phenylephrine required was recorded every minute until delivery of the baby and 3 min thereafter. Results: The correlations between parturients' baseline PI with the degree of decreases in systolic and mean arterial pressure (r = 0.81, P < 0.001 and r = 0.76, P < 0.001, respectively) and phenylephrine requirement (r = 0.761, p < 0.005) were recorded. This study identified that the patients with cut-off PI value of 3.2 were at higher risk for SA induced hypotension with a sensitivity of 85.9% and a specificity of 87.5% (P = 0.001). Conclusion: The patients with baseline cut-off perfusion index value of more than 3.2 were at higher risk for spinal anesthesia induced hypotension in elective cesarean section. [ABSTRACT FROM AUTHOR]

General Anaesthesia (GA) is accompanied by a marked decrease in sympathetic outflow and thus loss of vasomotor control of cardiac preload. The use of vasoconstriction during GA has mainly focused on maintaining blood pressure. Phenylephrine (PE) is a pure α1-agonist without inotropic effects widely used to correct intraoperative hypotension. The potential of PE for augmenting cardiac stroke volume (SV) and -output (CO) by venous recruitment is controversial and no human studies have explored the effects of PE in preload dependent circulation using indicator dilution technique. We hypothesized that PE-infusion in patients with cardiac stroke volume limited by reduced preload would restore preload and thus augment SV and CO. 20 patients undergoing GA for gastrointestinal surgery were monitored with arterial catheter and LiDCO unity monitor. Upon stable haemodynamics after induction patients were placed in head-up tilt (HUT). All patients became preload responsive as verified by a stroke volume variation (SVV) of > 12%. PE-infusion was then started at 15-20mikrg/min and adjusted until preload was restored (SVV < 12%). Li-dilution cardiac output (CO) was initially measured after induction (baseline), again with HUT in the preload responsive phase, and finally when preload was restored with infusion of PE.At baseline SVV was 10 ± 3% (mean ± st.dev.), CI was 2,6 ± 0,4 L/min*m2, and SVI 43 ± 7mL/m2. With HUT SVV was 19 ± 4%, CI was 2,2 ± 0,4 L/min*m2, SVI 35 ± 7mL/m2. During PE-infusion SVV was reduced to 6 ± 3%, CI increased to 2,6 ± 0,5 L/min*m2, and SVI increased to 49 ± 11mL/m2. All differences p < 0,001. In conclusion: Infusion of phenylephrine during preload dependency increased venous return abolishing preload dependency as evaluated by SVV and increased cardiac stroke volume and -output as measured by indicator-dilution technique. (ClinicalTrials.gov NCT05193097). [ABSTRACT FROM AUTHOR]

Background: Bleeding during nose surgery is very important, because it can cause a problem in the surgeon's field of view and lead to an increase in the probability of surgical complications. The aim of this study was to compare the local effects of tranexamic acid and phenylephrine on bleeding in rhinoplasty. Methods: The present study is a double-blind clinical trial in which 98 patients who were candidates for rhinoplasty Shiraz were randomly divided into 49 groups of phenylephrine and tranexamic acid. In the first group, 1 cc of phenylephrine and in the second group, 1 cc of tranexamic acid was used locally and then the variables in the two groups were compared. The current study was approved by the Iranian Clinical Trial Registration Center with code IRCT20201205049602N1. Results: The average blood pressure and heart rate in the phenylephrine group first increased and then decreased, but in the tranexamic acid group decreased from the beginning to 30 minutes. Based on the results of the test, there was a difference between the two groups in terms of the amount of bleeding, and a statistically significant relationship was observed. The average bleeding volume was lower in the phenylephrine group (p<0.0001). Conclusion: Results of this study showed that the amount of bleeding in the phenylephrine group was lower than that of tranexamic acid. It is recommended to use phenylephrine in rhinoplasty surgery to reduce bleeding and improve the surgeon's vision. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein‐coupled receptor P2Y1 receptors, increasing intracellular Ca2+ that activates small conductance calcium‐activated potassium (SKCa) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α‐adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α‐adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon.Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally.The α1‐adrenoceptor agonist phenylephrine (PE) (10−8–10−5 M) evoked concentration‐dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid‐circular colon at low PE concentrations, a contraction sensitive to 10−5 M phentolamine (non‐selective α‐adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10−6 M), and atropine (10−6 M) was recorded. PE‐induced relaxations were insensitive to TTX (10−6 M) and the nonselective β‐adrenoceptor blocker propranolol (10−6 M). In contrast, PE‐induced relaxations were blocked by phentolamine (10−5 M), prazosin (10−6 M) (α1‐adrenoceptor blocker), and RS17053 (10−6 M) (α1A‐blocker), but not by yohimbine (10−6 M) (α2‐adrenoceptor blocker). Apamin (10−6 M), a SKCa channel blocker, abolished PE‐induced relaxations.Contractile responses in the circular muscle of the mid colon could be attributed to α‐adrenoceptors located on enteric cholinergic neurons. Stimulation of α1A‐adrenoreceptors activates SKCa channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y1 receptors. [ABSTRACT FROM AUTHOR]

Ricinodendron heudelotii is a plant of the Euphorbiaceae family, used in traditional medicine to treat numerous diseases, including high blood pressure. The aim of this study is to evaluate the antioxidant and vasorelaxant effects of the aqueous extract of the stem bark of R. heudelotii. The pharmacological studies were carried out using the aqueous extract obtained by infusion. The antioxidant capacity of R. heudelotii was assessed by in vitro tests with DPPH (2,2‐diphenyl‐1‐picryl‐hydrazyl), ABTS (2,2 ′‐azino‐bis (3‐ethylbenz‐thiazoline‐6‐sulfonic acid), iron‐reducing capacity (FRAP), and inhibition of nitric oxide (NO) release. In vitro studies, the aortic rings obtained from adult Wistar albino rats of both sexes were used to determine the vasorelaxant effects of the extract of R. heudelotii on the NO and prostacyclin (PGI2) pathways as well as its involvement on various potassium channels were determined on intact or naked fragments of rat aorta precontracted with phenylephrine (10-6 M) or KCl (60 mM). The aqueous extract of R. heudelotii exhibited a remarkable DPPH (EC50: 1.68 μg/mL) and ABTS (EC50: 106.30 μg/mL) and nitric oxide (53.71% inhibition at 1000 μg/mL) radical scavenging activities as well as reducing power (absorbance of 1.56 at 1000 μg/mL). The nitric oxide inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME), and prostacyclin inhibitor, indomethacin, significantly attenuated the vasodilatory effect of R. heudelotii. Tetraethylammonium could not inhibit the vasodilatory effect of the extract, unlike glibenclamide and barium chloride. Ricinodendron heudelotii extract possesses antioxidant properties and vasorelaxing effect linked to endothelium‐related factors, and this relaxation was partially mediated mainly through the inhibition of Kir and KATP channels. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion Nasal anaesthetic‐decongestant sprays are commonly used prior to nasal instrumentation, such as flexible and rigid nasal endoscopy. Co‐phenylcaine (lignocaine 5%, phenylephrine 0.5%, ENT Technologies Pty Ltd., Melbourne, VIC, Australia) is a combination spray commonly used for this purpose. However, lignocaine is less potent than other local anaesthetics, and both active constituents of Co‐phenylcaine have a bitter taste. It was hypothesised that a combination spray containing tetracaine and oxymetazoline would both offer more potent topical anaesthesia and have a better taste.Four anaesthetic‐decongestant nasal sprays were tested in 10 healthy participants (Co‐phenylcaine, and tetracaine 0.5%, 1% and 2% with oxymetazoline 0.05%). Sensory thresholds were sequentially measured at the head of the inferior turbinate using Semmes‐Weinstein monofilaments over the following hour. Participants also rated taste on a Likert‐style scale, and reported whether they experienced subjective numbness of the maxillary teeth.A median peak sensory threshold of 60 g (the maximum tested) was observed with Co‐phenylcaine, but this threshold was exceeded by all the tetracaine‐based sprays. Tetracaine 2% with oxymetazoline 0.05% had a significantly more rapid onset than Co‐phenylcaine (4 min vs. 6 min, p < 0.05) and a longer duration of action. Eight participants reported dental numbness after administration of tetracaine 2% with oxymetazoline 0.05%, but only one participant after Co‐phenylcaine. Tetracaine‐based sprays were generally perceived to taste less unpleasant than Co‐phenylcaine.Tetracaine 2% with oxymetazoline 0.05% is a more potent and rapidly acting anaesthetic‐decongestant spray than Co‐phenylcaine, with a longer duration of action. [ABSTRACT FROM AUTHOR]

Background: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. Methods: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. Results: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06–5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19–12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. Conclusions: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban. [ABSTRACT FROM AUTHOR]

Background Objective Results Conclusion Changes in K+ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K+ channels. Their involvement in hydrogen sulfide (H2S)‐mediated vasorelaxation is still unclear, and data about human vessels are limited.To determine the role of K+ channel subtypes in the vasorelaxant mechanism of H2S donor, sodium‐hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).NaHS (1 × 10−6–3 × 10−3 mol/L) induced a concentration‐dependent relaxation of HIMA pre‐contracted by phenylephrine and high K+. Among K+ channel blockers, iberiotoxin, glibenclamide, 4‐aminopyridine (4‐AP), and margatoxin significantly inhibited NaHS‐induced relaxation of phenylephrine‐contracted HIMA (P < 0.01), whereas in the presence of apamin/1‐[(2‐chlorophenyl) diphenylmethyl]‐1H‐pyrazole (TRAM‐34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L‐NAME and KT5823, and by cyclo‐oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM‐34 and glibenclamide caused further decrease in NaHS‐induced vasorelaxation (P < 0.01), while iberiotoxin, 4‐AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01).Our results demonstrated that H2S donor, NaHS, induced concentration‐dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H2S included direct or indirect opening of different K+ channel subtypes, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the simultaneous response of the cerebral and skeletal muscle microvasculature to the same phenylephrine (PE) boluses. A hybrid optical system that combines hyperspectral near‐infrared spectroscopy (hs‐NIRS) and diffuse correlation spectroscopy (DCS) was used to monitor changes in tissue oxygenation and perfusion. Data were collected from the head and hind limb of seven male Sprague–Dawley rats while administering intravenous (IV) injections of PE or saline to all animals. The response to saline was used as a control. Skeletal muscle oxygenation decreased significantly after PE injection, while a statistically underpowered decrease in perfusion was observed, followed by an increase beyond baseline. Vascular conductance also decreased in the muscle reflecting the drug's vasoconstrictive effects. Tissue oxygenation and perfusion increased in the brain in response to PE. Initially, there was a sharp increase in cerebral perfusion but no changes in cerebral vascular conductance. Subsequently, cerebral flow and vascular conductance decreased significantly below baseline, likely reflecting autoregulatory mechanisms to manage the excess flow. Further, fitting an exponential function to the secondary decrease in cerebral perfusion and increase in muscular blood flow revealed a quicker kinetic response in the brain to adjust blood flow. In the skeletal muscle, PE caused a transient decrease in blood volume due to vasoconstriction, which resulted in an overall decrease in hemoglobin content and tissue oxygen saturation. Since PE does not directly affect cerebral vessels, this peripheral vasoconstriction shunted blood into the brain, resulting in an initial increase in oxygenated hemoglobin and oxygen saturation. [ABSTRACT FROM AUTHOR]

Introduction: The use of push-dose vasopressors to treat anesthesia-induced hypotension is a common evidence-based practice among anesthesiologists. In more recent years, the use of push-dose vasopressors has transitioned to the emergency department (ED) and critical care setting. There is debate on the best choice of a push-dose vasopressor, with push-dose epinephrine or phenylephrine being more commonly used. This scoping review evaluated publications regarding the clinical use of push-dose norepinephrine. Methods: We queried research studies in both PubMed and Google Scholar on the use of push-dose norepinephrine in human subjects, with numerous randomized controlled trials that compare norepinephrine to other vasopressors including phenylephrine, ephedrine, and epinephrine. Results: A large majority of the studies were performed in the setting of spinal anesthesia prior to cesarean section, while several involved the administration of general anesthesia, with limited-to-no literature in the emergency and critical care setting. Of the 27 studies that we included in the review, 17 were randomized controlled trials. These studies demonstrated that norepinephrine was safe and effective. Conclusion: Prior research has demonstrated the superiority of norepinephrine as a pressor of choice for various shock states. In this review, the safety and efficacy of push-dose norepinephrine is demonstrated, and favorable hemodynamic markers are shown in comparison to other agents. In addition, there are some safety and efficiency benefits to using push-dose norepinephrine from an administration standpoint, as well as clinically in decreased need for repeat doses. Further high-quality studies in the emergency and critical care realm would be beneficial to confirm these findings. [ABSTRACT FROM AUTHOR]

Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia (S p O 2 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia (P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation. NEW & NOTEWORTHY: This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals. [ABSTRACT FROM AUTHOR]