Pre-arrest hypothermia improved cardiac function of rats by ameliorating the myocardial mitochondrial injury after cardiac arrest

Abstract

This study investigated the effects of hypothermia induced before cardiac arrest or after return of spontaneous circulation (ROSC) on cardiac function and myocardial mitochondrial injury after ROSC in a rat cardiac arrest model. Sixty healthy, male Wistar rats were randomly divided into the Normothermia group, pre-arrest hypothermia (Pre-HT) group, and post-resuscitation hypothermia (Post-HT) group. The rats underwent 8 min of untreated ventricular fibrillation followed by cardiopulmonary resuscitation. Twelve rats in each group were used to evaluate the left ventricular ejection fraction before ventricular fibrillation and 4 h after ROSC. Survival was determined at 24 h after ROSC. The remaining eight rats in each group were used to detect for heart malondialdehyde, reduced glutathione, adenosine triphosphate levels and mitochondrial histology. Oxygen consumption rate and mitochondrial membrane potential were evaluated 4 h after ROSC; 10 of 12 rats in Pre-HT group, 5 of 12 in Post-HT group, and 6 of 12 in normothermia group were successfully resuscitated. The survival rate of each group was 66.7%, 33.3%, and 25%, respectively. Rats in the Pre-HT group showed less alteration of the mitochondrial ultrastructure and oxidative stress injury, better maintenance of adenine nucleotides, and more preservation of the mitochondrial membrane potential and respiratory function when compared with rats in the Post-HT and normothermia groups. Transient hypothermia is an effective preconditioning stimulus to induce ischemic tolerance in a cardiac arrest model and worthy of further evaluation for potential clinical use.

Impact statement

In this paper, we investigated the effects of hypothermia induced before ischemia or after ROSC on cardiac function, oxidative stress damage, and myocardial mitochondrial ischemia–reperfusion injury after cardiac arrest in a rat model with VF. We demonstrated that pre-arrest hypothermia conferred greater cardio-protective benefits than delayed post-resuscitation hypothermia, reduced the number of defibrillations required and dosages of epinephrine during CPR, decreased oxidative stress, ameliorated mitochondrial dysfunction, and subsequently improved survival rate.