Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17min of untreated cardiac arrest

Abstract

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs.

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

“…In a recent study characterizing cerebral recovery from asphyxial arrest in swine, mitochondrial respiration remained depressed even after ROSC and 4 hours of recovery(35). Previous experiments demonstrated favorable neurologic outcomes after prolonged CA that continued to improve 24 hours post-ROSC, emphasizing a delayed period of neurologic recovery that may extend well beyond the duration of this investigation(5–7). …”

“…Our laboratory applied IPC during CPR in a porcine model of prolonged whole-body ischemia during ventricular fibrillation (VF) CA. Pauses in chest compressions during the first 2 minutes of CPR improved left ventricular ejection fraction (LVEF) following return of spontaneous circulation (ROSC) and increased neurologically favorable survival after 48 hours(5–7). These data demonstrate that the method of initial reperfusion with CPR has an impact on the extent of injury after prolonged cardiac arrest.…”

PEO–PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture

“…P188 reduced membrane leakage, apoptosis, and loss of mitochrondrial polarization, but had no impact on lipid peroxidation, upon simulated ischemia/reperfusion in cardiac myocytes 12 . P188 reduced infarct volume, motor deficits, and death after ischemia/reperfusion in mice 17 ; improved recovery to myocardial infarction 18 and cardiac arrest in pigs; 19 prolonged survival and reduced tissue damage upon hypotensive resuscitation in rats; 20 and enhanced survival time after severe hemorrhage in pigs. 21 In mice, P188 reduced intracerebral hemorrhage injury volume and reduced neurological symptoms; 22 improved blood-brain barrier integrity after traumatic brain injury; 23 and resealed cells in the cortex and hippocampus after controlled cortical impact.…”

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post–Cardiac Arrest Rat: A Novel Metabolic Phenotype

“…There are promising clinical treatments, such as therapeutic hypothermia, ischemic postconditioning, and controlled reperfusion, which improve survival in preclinical studies and are hypothesized to address postresuscitation metabolic disorders 10, 11, 12, 13. However, there are a number of randomized controlled clinical trials that show no benefit,14, 15, 16, 17, 18 in part as a result of the lack of an ability to differentiate patients with treatable metabolic injury, patients who might live with proper treatment, from patients who do not have a metabolic injury, patients who will live, or from patients with untreatable metabolic injury, patients who will not live 4, 19, 20, 21…”