Dataset Information

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

ABSTRACT: Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR).A total of 63 swine were randomized to no ischemia (Naïve), 19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR. Mitochondria were isolated from the heart and brain to quantify respiration, rate of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species (ROS) production was quantified from fresh frozen heart and brain tissue.Compared to Naïve, Untreated VF induced cardiac and brain ROS overproduction concurrent with decreased mitochondrial respiratory coupling and CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR attenuated brain ROS overproduction but had no other effect on mitochondrial function in the heart or brain. Compared to Untreated VF, IPC-CPR improved cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and decreased ROS overproduction in the heart and brain.Fifteen minutes of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and increased ROS production in the heart and brain. IPC-CPR attenuates cardiac mitochondrial dysfunction caused by prolonged VF CA after only 4min of reperfusion, suggesting that IPC-CPR is an effective intervention to reduce cardiac injury. However, reperfusion with both CPR methods had limited effect on mitochondrial function in the brain, emphasizing an important physiological divergence in post-arrest recovery between those two vital organs.

SUBMITTER: Matsuura TR

PROVIDER: S-EPMC5552370 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

Matsuura Timothy R TR Bartos Jason A JA Tsangaris Adamantios A Shekar Kadambari Chandra KC Olson Matthew D MD Riess Matthias L ML Bienengraeber Martin M Aufderheide Tom P TP Neumar Robert W RW Rees Jennifer N JN McKnite Scott H SH Dikalova Anna E AE Dikalov Sergey I SI Douglas Hunter F HF Yannopoulos Demetris D

Resuscitation 20170410

<h4>Background</h4>Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, ha ...[more]

PMID: 28408349

Similar Datasets

Project description:To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest.Laboratory investigation.University laboratory.Pigs.Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation.A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages.In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Project description:BackgroundDespite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats.MethodsRats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated.ResultsThe survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan-Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in D-glutamine and D-glutamate metabolism.ConclusionsH2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia-reperfusion injury in critically ill patients who require ECMO support.

Project description:BackgroundVeno-arterial extracorporeal membrane oxygenation has increasingly emerged as a feasible treatment to mitigate the progressive multiorgan dysfunction that occurs during cardiac arrest, in support of further resuscitation efforts.ObjectivesBecause the recent systematic review commissioned in 2018 by the International Liaison Committee on Resuscitation Advanced Life Support task did not include studies without a control group, our objective was to conduct a review incorporating these studies to increase available evidence supporting the use of extracorporeal cardiopulmonary resuscitation (ECPR) for cardiac arrest patients, while waiting for high-quality evidence from randomized controlled trials (RCTs).MethodsMEDLINE, Embase, and Science Citation Index (Web of Science) were searched for eligible studies from database inception to July 20, 2020. The population of interest was adult patients who had suffered cardiac arrest in any setting. We included all cohort studies with 1 exposure/1 group and descriptive studies (ie, case series studies). We excluded RCTs, non-RCTs, and observational analytic studies with a control group. Outcomes included short-term survival and favorable neurological outcome. Short-term outcomes (ie, hospital discharge, 30 days, and 1 month) were combined into a single category.ResultsOur searches of databases and other sources yielded a total of 4302 citations. Sixty-two eligible studies were included (including a combined total of 3638 participants). Six studies were of in-hospital cardiac arrest, 34 studies were of out-of-hospital cardiac arrest, and 22 studies included both in-hospital and out-of-hospital cardiac arrest. Seven hundred and sixty-eight patients of 3352 (23%) had short-term survival; whereas, 602 of 3366 (18%) survived with favorable neurological outcome, defined as a cerebral performance category score of 1 or 2.ConclusionsCurrent clinical evidence is mostly drawn from observational studies, with their potential for confounding selection bias. Although studies without controls cannot supplant case-control or cohort studies, several ECPR studies without a control group show successful resuscitation with impressive results that may provide valuable information to inform a comparison.

Project description:BackgroundMild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia.Methodology/principal findingsThirty pigs (28-34 kg) were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21), coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34+/-7 versus 57+/-12%; p<0.05) and improved left ventricular function compared to normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune cell infiltration, (ii) apoptosis, (iii) IL-1beta and IL-6 mRNA up-regulation, and (iv) IL-1beta protein expression (p<0.05). Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached.Conclusions/significanceHypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and pro-inflammatory cytokine expression.

Project description:IntroductionIn this study, we sought to examine whether pharmacological postconditioning with sevoflurane (SEVO) is neuro- and cardioprotective in a pig model of cardiopulmonary resuscitation.MethodsTwenty-two pigs were subjected to cardiac arrest. After 8 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started. After successful return of spontaneous circulation (N = 16), animals were randomized to either (1) propofol (CONTROL) anesthesia or (2) SEVO anesthesia for 4 hours. Neurological function was assessed 24 hours after return of spontaneous circulation. The effects on myocardial and cerebral damage, especially on inflammation, apoptosis and tissue remodeling, were studied using cellular and molecular approaches.ResultsAnimals treated with SEVO had lower peak troponin T levels (median [IQR]) (CONTROL vs SEVO = 0.31 pg/mL [0.2 to 0.65] vs 0.14 pg/mL [0.09 to 0.25]; P < 0.05) and improved left ventricular systolic and diastolic function compared to the CONTROL group (P < 0.05). SEVO was associated with a reduction in myocardial IL-1? protein concentrations (0.16 pg/?g total protein [0.14 to 0.17] vs 0.12 pg/?g total protein [0.11 to 0.14]; P < 0.01), a reduction in apoptosis (increased procaspase-3 protein levels (0.94 arbitrary units [0.86 to 1.04] vs 1.18 arbitrary units [1.03 to 1.28]; P < 0.05), increased hypoxia-inducible factor (HIF)-1? protein expression (P < 0.05) and increased activity of matrix metalloproteinase 9 (P < 0.05). SEVO did not, however, affect neurological deficit score or cerebral cellular and molecular pathways.ConclusionsSEVO reduced myocardial damage and dysfunction after cardiopulmonary resuscitation in the early postresuscitation period. The reduction was associated with a reduced rate of myocardial proinflammatory cytokine expression, apoptosis, increased HIF-1? expression and increased activity of matrix metalloproteinase 9. Early administration of SEVO may not, however, improve neurological recovery.

Dataset Information

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

Publications

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets