Abstract 169: Erythropoietin Enhances Left Ventricular Cytochrome c Oxidase Activity During Cardiac Resuscitation
Background: We have previously documented in a rat model of VF and closed-chest resuscitation that administration of erythropoietin (EPO) preserves left ventricular distensibility — yielding hemodynamically more effective CPR — and attenuates post-resuscitation myocardial dysfunction. EPO has been shown to activate and translocate protein kinase C epsilon (PKCå) from the cytosol to the mitochondria; and PKCå activation — in preconditioning studies — has been associated with activation of cytochrome c oxidase (COX; i.e., complex IV of the electron transport chain).
Hypothesis: Given that similar functional myocardial benefits can be elicited by preservation of mitochondrial bioenergetic function, we hypothesized that EPO could mediate the aforementioned myocardial effects in part by activating COX.
Methods: VF was electrically induced in 10 Sprague-Dawley male rats and left untreated for 8 minutes before attempting resuscitation by 8 minutes of closed-chest resuscitation and delivery of electrical shocks. Rats were randomized to receive 5,000 U/kg of EPO (n = 5) or saline vehicle (n = 5) into the right atrium immediately before starting closed-chest resuscitation, with the investigators blind to the assignment. All rats were resuscitated and survived 120 minutes, time at which the hearts were removed storing the left ventricles at −80°C. Mitochondria were isolated from frozen tissue and COX activity measured using a technique based on determining the oxidation rate of externally supplied reduced cytochrome c (absorbance at 550 nm). COX activity was measured in unlysed and lysed mitochondria to determine outer mitochondrial membrane (OMM) integrity.
Results: Hearts treated with EPO had a 40% higher COX activity than control hearts and higher percentage of mitochondria with intact OMM (Figure).
Conclusions: EPO improved left ventricular COX activity; an effect that could be central to the protective effect of EPO during resuscitation from cardiac arrest.
- © 2010 by American Heart Association, Inc.