Abstract 71: The Effect of Achieving Return of Spontaneous Circulation on Mitochondrial Respiration Following Prolonged Cardiac Arrest
Introduction: Ischemia and reperfusion injury have been shown to alter mitochondrial function. Respiration, a primary function of mitochondria and marker of mitochondrial health, was previously believed to be unrecoverable after prolonged cardiac arrest. We investigated the effect that return of spontaneous circulation (ROSC) has on the mitochondrial respiratory profile of the myocardium.
Methods: After 15 minutes of untreated ventricular fibrillation (VF), 16 pigs received mechanical CPR and intravenous epinephrine per standard AHA protocols. Defibrillation was first attempted after 4 minutes of CPR. In the event of persistent VF or pulseless electrical activity, CPR was continued for up to 15 minutes with epinephrine and defibrillations administered every 3 minutes. Animals that had ROSC were sacrificed 15 minutes after the initiation of resuscitation efforts. Another 6 animals were used as non-ischemic controls and had no cardiac arrest. Cardiac mitochondria were isolated. Respiration for complex I and complex II substrates was measured. Respiratory control index (RCI) was calculated as the ratio of state 3 to state 4 respiration. Mean RCI were compared via t-test and ANOVA. A p-value of < 0.05 was considered significant.
Results: ROSC was achieved in 10 of 16 animals. Fifteen minutes after initiation of resuscitation efforts, animals that achieved ROSC had significantly higher complex I RCI compared to animals with ongoing CPR (8.0±0.8 vs. 4.3±0.4, p<0.01). Complex I RCI in animals that achieved ROSC recovered to that of non-ischemic controls (8.0±0.8 vs. 6.3±0.5, p=0.17). Complex II RCI did not differ between ROSC, CPR, and non-ischemic controls (3.2±0.3 vs. 2.7 ±0.2 vs. 3.2±0.1, respectively; p=0.40).
Conclusion: Achieving ROSC after prolonged untreated cardiac arrest leads to normalization of mitochondrial respiration within 15 minutes of the initiation of resuscitation efforts. At the same time, complex I RCI is suppressed and complex II RCI is unaffected during ongoing CPR. Decreased mitochondrial complex I respiration during ongoing CPR could be the cause or the effect of the absence of ROSC. Further investigation is needed.
Author Disclosures: T.R. Matsuura: None. J.A. Bartos: None. G. Debaty: None. S.H. McKnite: None. J.N. Rees: None. M.L. Riess: Research Grant; Modest; Department of Veterans Affairs CARA-026-10F, NIH 5R01HL098490-03. D. Yannopoulos: Research Grant; Modest; NIH 1R01HL108926, NIH 1R01HL123227.
- © 2014 by American Heart Association, Inc.