Abstract 287: Erythropoietin Enables Mitochondria to Preserve Oxidative Phosphorylation Under Conditions of Calcium Overload and Oxidative Stress
Introduction: We previously reported in rats that a single bolus dose of erythropoietin (Epo) given at the start of CPR enhanced, within minutes, the efficacy of chest compression. The effect was attributed to attenuation of reductions in left ventricular distensibility; an effect previously linked to preservation of mitochondrial bioenergetic function.
Hypothesis: We now investigated whether Epo could enable mitochondria to maintain oxidative phosphorylation under conditions of calcium overload and oxidative stress, which are central to injury caused by ischemia and reperfusion.
Methods: Mitochondria were isolated from the left ventricle of hearts harvested from groups of rats (n=3) that received during spontaneous circulation no Epo or received Epo (5,000 U/kg) in bolus dose into the right atrium at 60, 240, and 480 seconds before harvest. Separate aliquots of mitochondria were subjected to incremental concentrations of calcium (1.5, 12.5, and 25 µM free calcium) or tert-butyl hydroperoxide (250 and 5000 µM). Phosphate:oxygen (P:O) ratios were then measured in a respiration chamber (MT 200, Mitocell, Strathkelvin Instruments).
Results: Epo, in a time dependent manner, prevented reductions in P:O ratios observed when mitochondria were exposed to incremental concentrations of calcium or tert-butyl hydroperoxide (Table).
Conclusions: Preservation of left ventricular myocardial distensibility could partly result from a favorable effect of Epo enabling mitochondria to resist injury caused by calcium overload and oxidative stress, and within a response time sufficiently rapid to favorably impact cardiac resuscitation.
- © 2011 by American Heart Association, Inc.