Abstract
Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA). Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF). We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.
Highlights
Postcardiac arrest brain injury is a common cause of morbidity and mortality in postcardiac arrest patients [1], leading to death in 68% of patients after out-of-hospital cardiac arrest [2] and significant cerebral dysfunction in survivors [1]
At the end of 15 min of cardiac arrest (CA), the aortic diastolic pressure in the cardiopulmonary resuscitation (CPR) group was maintained between 26 and 28 mmHg as previously described, whereas the aortic pressure in the ischemia group was maintained at approximately 10 mmHg due to the remaining elastic properties of the arterial wall
The respiratory control ratio (RCR) of the CPR group was 20% and 19% lower than that of the sham group, but it was significantly higher than that of the ischemia group (P < 0.01). This suggests that CPR protects the mitochondrial respiratory function of rat neurons during CA
Summary
Postcardiac arrest brain injury is a common cause of morbidity and mortality in postcardiac arrest patients [1], leading to death in 68% of patients after out-of-hospital cardiac arrest [2] and significant cerebral dysfunction in survivors [1]. Accumulating data have shown that mitochondria, the crucial cellular organelles for energy production, play a critical role as effectors and targets of ischemia and reperfusion injury after cardiac arrest (CA) [3, 4]. Our group [5] and others [6,7,8] have demonstrated the impaired myocardial mitochondrial dysfunction and ultrastructural alterations of mitochondria developed during CA and following return of spontaneous circulation (ROSC). These observations suggested that an impaired functional capacity of myocardial mitochondria plays a pivotal role in the development of postresuscitation myocardial dysfunction. Gazmuri et al reported that the strategies of preserving mitochondrial bioenergetic function in the myocardium by using inhibitors of the sodium-hydrogen
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