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Background: Acute respiratory distress syndrome (ARDS) remains a significant challenge in critical care, with high mortality rates despite advancements in treatment. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is employed as salvage therapy for refractory cases. However, some patients may continue to experience persistent severe hypoxemia despite being treated with VV-ECMO. To achieve this, moderate hypothermia and short-acting selective β1-blockers have been proposed., Methods: Using a swine model of severe ARDS treated with VV-ECMO, this study investigated the efficacy of moderate hypothermia or β-blockade in improving arterial oxygen saturation (SaO 2 ) three hours after VV-ECMO initiation. Primary endpoints included the ratio of VV-ECMO flow to cardiac output and arterial oxygen saturation before VV-ECMO start (H0) and three hours after ECMO start (H3). Secondary safety criteria encompassed hemodynamics and oxygenation parameters., Results: Twenty-two male pigs were randomized into three groups: control (n = 6), hypothermia (n = 9) and β-blockade (n = 7). At H0, all groups demonstrated similar hemodynamic and respiratory parameters. Both moderate hypothermia and β-blockade groups exhibited a significant increase in the ratio of VV-ECMO flow to cardiac output at H3, resulting in improved SaO 2 . At H3, despite a decrease in oxygen delivery and consumption in the intervention groups compared to the control group, oxygen extraction ratios across groups remained unchanged and lactate levels were normal., Conclusions: In a swine model of severe ARDS treated with VV-ECMO, both moderate hypothermia and β-blockade led to an increase in the ratio of VV-ECMO flow to cardiac output resulting in improved arterial oxygen saturation without any impact on tissue perfusion., (© 2024. The Author(s).)

Hemodynamic instability in postresuscitation syndrome worsens survival and neurological outcomes. Venoarterial extracorporeal membrane oxygenation (VA ECMO) for refractory cardiac arrest might improve outcomes. Hemodynamical support under VA ECMO relies on norepinephrine and crystalloids. The present work aims to assess the effects of albumin (ALB) infusion in a swine model of ischemic refractory cardiac arrest implanted by VA ECMO. Cardiac arrest was performed in 18 pigs and VA ECMO was initiated after 30 minutes cardiopulmonary resuscitation (CPR). Pigs were randomly assigned to standard care (norepinephrine + crystalloids) versus ALB group (ALB + standard care). Hemodynamical assessments were performed over 6 hours. Severe hypoalbuminemia was observed in the control group and could be reversed with ALB infusion. Total crystalloid load was significantly reduced with ALB infusion (1,000 [1,000-2,278] ml vs. 17,000 [10,000-19,000] ml, ALB versus control group, respectively, p < 0.001). There was no significant impact with regard to lactate clearance (29.16% [12.5-39.32] and 10.09% [6.78-29.36] for control versus ALB groups, respectively, p = 0.185), sublingual capillary microvascular parameters, or cerebral near-infrared spectrometer (NIRS) values. Compared to standard care, ALB infusion was highly effective in reducing fluid loading in a porcine model of postresuscitation syndrome after refractory cardiac arrest treated with VA ECMO., Competing Interests: Disclosure: B.L. received fees or grants from Abiomed, Getinge, Orion, Amomed, Sanofi, and Baxter. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: The current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model., Methods: In 10 pigs (63-73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH 2 O; (2) TCAV group with P-high set between 27 and 29 cmH 2 O, P-low at 0 cmH 2 O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3-4 s, with I:E > 6:1., Results: Both lung elastance and PaO 2 :FiO 2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group ( p < 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group ( p < 0.05)., Conclusion: No hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lescroart, Pequignot, Bitker, Pina, Tran, Hébert, Richard, Lévy and Koszutski.)

Background: Adjusting drug therapy under veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging. Although impaired pharmacokinetics (PK) under VV ECMO have been reported for sedative drugs and antibiotics, data about amiodarone are lacking. We evaluated the pharmacokinetics of amiodarone under VV ECMO both in vitro and in vivo., Methods: In vitro: Amiodarone concentration decays were compared between closed-loop ECMO and control stirring containers over a 24 h period. In vivo: Potassium-induced cardiac arrest in 10 pigs with ARDS, assigned to either control or VV ECMO groups, was treated with 300 mg amiodarone injection under continuous cardiopulmonary resuscitation. Pharmacokinetic parameters C max , T max AUC and F were determined from both direct amiodarone plasma concentrations observation and non-linear mixed effects modeling estimation., Results: An in vitro study revealed a rapid and significant decrease in amiodarone concentrations in the closed-loop ECMO circuitry whereas it remained stable in control experiment. In vivo study revealed a 32% decrease in the AUC and a significant 42% drop of C max in the VV ECMO group as compared to controls. No difference in T max was observed. VV ECMO significantly modified both central distribution volume and amiodarone clearance. Monte Carlo simulations predicted that a 600 mg bolus of amiodarone under VV ECMO would achieve the amiodarone bioavailability observed in the control group., Conclusions: This is the first study to report decreased amiodarone bioavailability under VV ECMO. Higher doses of amiodarone should be considered for effective amiodarone exposure under VV ECMO.

Background: Refractory cardiac arrest management relies on extracorporeal cardiopulmonary resuscitation (ECPR), requiring the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Circulatory flow recovery can be associated with an ischemia-reperfusion injury, leading to vasoplegia and vasopressor requirement. The aim of this work was to evaluate the impact on hemodynamics of a methylene blue bolus infusion in a porcine model of ischemic refractory cardiac arrest., Methods: Ischemic refractory cardiac arrest was induced in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and the pigs were randomly assigned to the standard care group (norepinephrine + crystalloids) or methylene blue group (IV 2 mg·kg -1 bolus of methylene blue over 30 min + norepinephrine and crystalloids). Macrocirculatory parameters and lactate clearance were measured. Sublingual microcirculation was evaluated with sidestream dark field (SDF) imaging. The severity of the ischemic digestive lesions was assessed according to the histologic Chiu/Park scale., Results: Eighteen pigs were included. The total crystalloid load (5000 (6000-8000) mL vs. 17,000 (10,000-19,000) mL, p = 0.007, methylene blue vs. standard care group) and catecholamine requirements (0.31 (0.14-0.44) μg·kg -1 ·min -1 vs. 2.32 (1.17-5.55) μg·kg -1 ·min -1 , methylene blue vs. standard care group, p = 0.004) were significantly reduced in the methylene blue group. There were no significant between-group differences in lactate clearance, sublingual capillary microvascular parameters assessed by SDF or histologic Chiu/Park scale., Conclusions: In our refractory cardiac arrest porcine model treated with ECPR, methylene blue markedly reduced fluid loading and norepinephrine requirements in comparison to standard care during the first 6 h of VA-ECMO.

Background: The choice of the best vasopressor after ExtraCorporeal Membrane Oxygenation (ECMO) implantation after cardiac arrest is not well defined. Circulatory flow recovery with ECMO is associated with vasoplegia and vasopressor need. The present study aimed to compare the effects of norepinephrine and vasopressin in the first 6 h after ECMO initiation., Methods: Cardiac arrest was induced in 20 pigs by coronary surgical ligature and veno-arterial-ECMO was started after a 30-min period of cardio-pulmonary resuscitation. Pigs were randomized into two groups, arginine vasopressin (AVP) or norepinephrine (NE), with the drugs titrated to maintain a mean arterial pressure (MAP) at 65 mm Hg. Macrocirculatory and metabolic parameters were assessed by lactate clearance. Microcirculatory parameters were assessed by sublingual microcirculation with Sidestream Dark Field imaging and peripheral Near InfraRed Spectroscopy. Pulmonary edema was evaluated by measuring lung wet/dry weight ratio., Results: No difference was found between groups regarding ECMO flow and MAP. Fluid resuscitation volume was higher in the NE group (14,000 [11,250-15,250] mL vs. 3,500 [1,750-4,000] mL in the AVP group, P < 0.05). Lung wet/dry weight ratio was higher in the Norepinephrine group. Lactate clearance between H0 and H6 was higher in the AVP group (47.84 [13.42-82.73]% vs. the NE group 25.66 [-7.31 to 35.34)% vs. P < 0.05). No significant difference was observed for sublingual microcirculation values. Baseline tissue oxygen saturation was comparable and higher at both H3 and H6 in the Vasopressin group comparatively to the Norepinephrine group (P < 0.05). Renal and liver function evolution also remained similar in the two groups throughout the study., Conclusions: AVP administration in refractory cardiac arrest resuscitated by veno-arterial-ECMO is associated with a faster lactate clearance, less fluid resuscitation, and less pulmonary edema when compared with NE for similar global and regional hemodynamic effects., Competing Interests: The other authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Objective: This study was designed to assess the effect of two veno-arterial ExtraCorporeal Membrane Oxygenation (ECMO) blood-flow strategies in an experimental model of Extracorporeal Cardio-Pulmonary Resuscitation (ECPR) on macrocirculatory, metabolic and microcirculatory parameters in the first six hours of ECMO initiation., Methods: Cardiac arrest was induced in 18 pigs by surgical ligature of the left descending coronary artery followed by a low-flow time of 40 min using internal cardiac massage. ECPR was initiated in normothermia with an ECMO blood flow of 30-35 ml.kg -1 . min -1 (low-blood-flow group, LBF) or 65-70 ml.kg -1 . min -1 (standard-blood-flow group, SBF), with the same mean arterial pressure target of 65 mmHg adjusted with norepinephrine. Macrocirculatory and metabolic parameters were assessed by lactate clearance and carotid blood flow. Microcirculatory parameters were assessed by sublingual microcirculation with Sidestream Dark Field (SDF) imaging and peripheral Near-InfraRed Spectrometry (NIRS). Inflammatory cytokine levels were measured with a multicomplexed ELISA-based array platform., Results: There were no between-group differences at baseline and at ECMO initiation (H0). Lactate clearance at H6 was lower in LBF compared to SBF (6.67[-10.43-18.78] vs. 47.41[19.54-70.69] %, p = 0.04). Carotid blood flow was significantly lower (p<0.005) during the last four hours despite similar mean arterial pressure levels. For microvascular parameters, SDF and NIRS parameters were transitorily impaired at H3 in LBF. IL-6 cytokine level was significantly higher in LBF at the end of the experiment., Conclusion: In an experimental porcine model of refractory cardiac arrest treated by ECMO, a low-blood-flow strategy during the first six hours of resuscitation was associated with lower lactate clearance and lower cerebral blood flow with no benefits on ischemia-reperfusion parameters., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There is currently no recommendation for the mean arterial pressure target in the particular setting of Extracorporeal Cardiopulmonary Resuscitation (ECPR) in the first hours following cardiogenic shock complicated by cardiac arrest. This study aimed to assess the effects of two different levels of mean arterial pressure on macrocirculatory, microcirculatory, and metabolic functions., Design: Randomized animal study., Setting: University research laboratory., Intervention: Ventricular fibrillation was induced in 14 male pigs by surgical ligature of the interventricular coronary artery. After 20 min of cardiopulmonary resuscitation, Extracorporeal Life Support (ECLS) was initiated to restore circulatory flow. Thereafter, animals were randomly allocated to a high mean arterial pressure group (High-MAP, 80-85 mm Hg) or to a standard mean arterial pressure group (Standard-MAP, 65-70 mm Hg). Assessments conducted at baseline, immediately following and 6 h after ECLS initiation were focused on lactate evolution, amount of infused fluid, and microcirculatory parameters., Results: There was no significant difference between the two groups at the time of ECLS initiation and at 6 h with regard to lactate levels (High-MAP vs. Standard-MAP: 8.8 [6.7-12.9] vs. 9.6 [9.1-9.8] mmol·l, P = 0.779 and 8.9 [4.3-11.1] vs. 3.3 [2.4-11] mmol·l, P = 0.603). Infused fluid volume did not significantly differ between the two groups (4,000 [3,500-12,000] vs. 5,000 [2,500-18,000] mL, P = 0.977). There was also no significant difference between the two groups regarding renal and liver functions, and sublingual capillary microvascular flow index assessed by Sidestream Dark Field imaging., Conclusion: Compared with a standard mean arterial pressure regimen, targeting a high mean arterial pressure in the first hours of an experimental ECPR model did not result in any hemodynamic improvement nor in a decrease in the amount of infused fluid.

We report on cotunneling spectroscopy magnetoconductance measurements of multihole ultraclean carbon nanotube quantum dots in the SU(4) Kondo regime with strong spin-orbit coupling. Successive shells show a gradual weakening of the Kondo effect with respect to the spin-orbital splittings, leading to an evolution from SU(4) to SU(2) symmetry with a suppressed conductance at half-shell filling. The extracted energy level spectrum, overall consistent with negligible disorder in the nanotube, shows in the half filled case large renormalizations due to Coulombian effects.

Aortic coarctation is the reflection of a wider vasculopathy affecting the precoarctation arterial tree. Patients should be screened for associated heart disease and anomalies of supra-aortic arch vessels. Treatment options include surgical repair or balloon angioplasty with or without stent-graft implantation. Both treatment options can be complicated by recoarctation or aortic aneurysms and warrant lifelong surveillance. In adults, anatomic correction of coarctation has fewer effects on arterial pressure than in infants. Thus, systemic hypertension may persist in up to half of treated patients. Recoarctation or unrecognized aortic arch hypoplasia should nevertheless be eliminated., (Copyright © 2013. Published by Elsevier Masson SAS.)

Background: The influence of the first immunization on cardiorespiratory (CR) stability in very preterm infants is still a controversial subject., Objectives: To describe the changes induced by immunization on heart and respiratory rate variability (HRV-RRV) and to test a potential association between preimmunization profiles and postimmunization CR events., Methods: Continuous 72-hour CR recordings and 2.5-hour polysomnographic recordings were performed on very preterm infants immunized after 7 weeks. The results are expressed as medians (interquartile ranges)., Results: Immunization was performed on 31 very preterm infants [28 weeks' gestation (26.9-29), birth weight: 965 g (795-1,105)], and was associated with an increased incidence (p < 0.01) of events lasting more than 10 s: bradycardia <80 bpm [2.2 (1.1-7) vs. 1.8 (1-4)/12 h], desaturation [17.6 (9.4-36.4) vs. 13.9 (7.7-33.8)/12 h] and associated bradycardia-desaturation [IB+D, 4.1 (1.4-7.3) vs. 2.4 (1-4.6)/12 h], with mild changes in HRV and no change in RRV. The changes in IB+D frequency were correlated with preimmunization IB+D frequency (r = 0.44, p < 0.05), HRV spectral parameter low frequency/high frequency ratio (LF/HF, r = 0.55, p < 0.01) and approximate entropy of HRV (r = -0.39, p < 0.05)., Conclusion: The increase in CR events after the first immunization in very preterm infants was associated with: (1) sympathetic predominance in heart rate control (high LF/HF ratio), (2) abnormal oversimplification of HRV (low entropy) and (3) persistent respiratory rhythm control immaturity (high IB+D before vaccine)., (Copyright © 2013 S. Karger AG, Basel.)

The liver is the most frequent and fatal site of distant spreading of colorectal cancer. Most liver metastases animal models involve nude mice and an injection of tumour cells through the spleen or portal vein, or orthotopic implantation of tumour cells in the colon wall. The aim of this study was to develop a reliable rat model of liver metastases with human colorectal HT29 cells. Seventy male athymic Rowett nude rats weighing 300+/-30 g were separated into three groups. The first group (n=20) consisted of untreated rats, rats in the second group (n=20) were immunosuppressed by cyclosporin A, and those in the third group (n=30) were irradiated the day before cell grafting. Tumour cells (2 x 10(7)) were subcapsulary injected into the liver, and rats were sacrificed after 60 days. The livers were excised, and tumours were serially sectioned to determine size and volume, then fixed for histological studies. The take-rate was 55% in the first group, 35% in the second and 74% in the third group. The mean volume of tumours in the first group was 537+/-162 mm(3), 613+/-232 mm(3) in the second group and 2949+/-629 mm(3) in the third group. In conclusion, subcapsular injection of the human colonic HT29 cancer cells into the liver of preoperatively irradiated nude rats is a reliable, reproducible and easily obtained model, which should be useful for preclinical studies.

Unlabelled: Most upper arm regional anesthesia techniques are successful and differences in efficacy should not dictate the choice of technique. In the present study, we compared humeral block (HB) and infraclavicular brachial plexus block (ICB) using anesthetic time (i.e., duration of the procedure + onset time) as the primary outcome measure. The block was successful when a complete sensory block was obtained in the four major nerves of the arm, and the time to complete block was recorded. Patients undergoing orthopedic surgery of the upper limb were included in a prospective randomized study and received ICB (group I, n = 60 patients) or HB (group H, n = 60 patients). Total anesthetic time was 19.5 min (95% confidence interval [CI], 17.4-21.6 min) for ICB and 20.8 min (95% CI, 18.7--22.9 min) for HB (not significant). Time to perform the block was 4.5 min (95% CI, 4-5 min) for ICB and 9.8 min (95% CI, 8.9--10.7 min) for HB (P < 0.05). The onset time was 15 min (95% CI, 13-17 min) for ICB and 11 min (95% CI, 9--13 min) for HB (P < 0.05). The success rate was 92% for ICB and 95% for HB (not significant). One self-limited vascular puncture was made in each group. HB had a faster onset time but ICB using a double-stimulation technique was faster to perform. Anesthetic time was similar with the two techniques., Implications: We have compared infraclavicular brachial plexus block (ICB) with humeral block. Efficacy and anesthetic time were not significantly different, although time to perform the block was shorter with the ICB.

Susac syndrome is an occlusive arteriolar disease that provokes infarcts in the cochlea, retina, and brain of young subjects, mostly women. Its cause is unknown. Some infarcts may be asymptomatic and only revealed by ancillary investigation: 1) audiogram that shows bilateral sensorineural hearing loss predominating on low frequencies, 2) funduscopy and fluorescein retinal angiography demonstrating bilateral distal branch retinal artery occlusions, and 3) brain MRI T2-weighted images disclosing small multifocal hyperintensities in white and gray matter. Treatment options are not codified, ranging from antithrombotic drugs to immunomodulatory therapy. Course is self-limited after an active fluctuating phase. Dementia, blindness, and deafness are rare late sequelae, and half of patients return to normal life.

The effect of an oral effervescent formulation combining 200 mg cimetidine and 1.8 g sodium citrate on gastric pH and volume were studied in patients undergoing caesarean section. Seventy-four patients undergoing elective (group 1) or emergency caesarean section (group 2) were included. Before entering the operating theater (5 to 60 min before intubation), they were given the tablet dissolved in 15 ml of water. Induction and maintenance of anaesthesia were carried out with conventional techniques. The patient's gastric content was aspirated just after endotracheal intubation, and before extubation. its pH and volume were measured at both times. Mean pH was similar in the two groups after intubation (6.07 +/- 1.13 in group 1; 5.52 +/- 1.14 in group 2) and before extubation (6.32 +/- 1.08 vs. 5.85 +/- 1.02 respectively). Gastric pH was therefore greater than 2.5 in all 74 patients at both times. Mean volumes of gastric content after intubation were greater in group 2 (32.7 +/- 23.9 ml vs. 21.6 +/- 15.8 ml; p less than 0.02). However, just before extubation, these were similar (15.0 +/- 15.4 ml in group 1, 20.1 +/- 14.9 ml in group 2). The percentage of patients in the 2 groups with gastric volumes greater than 25 ml at the time of intubation were not significantly different (29.7% vs. 45.9% respectively). No patient was at risk of developing pneumonitis in case of aspiration (gastric content pH less than 2.5 and volume greater than 25 ml), either during endotracheal intubation or extubation.(ABSTRACT TRUNCATED AT 250 WORDS)