Abstract 2524: Currently Optimized Cardioplegia Protocols Effective in the Male are Not as Efficacious in the Female: Mitochondrial Function and Calcium Concentration Diminish Cardioprotection in the Aged Female Heart
Background: The efficacy of cardioprotection has been shown to vary with age, however, little data is available on the effects of gender. Recent studies have shown that aged women have a significantly greater risk potential as compared to aged men and that women have worse outcomes after cardiac surgery. Previously, we have shown that cardioplegia modulates ischemia and that the addition of diazoxide enhances cardioprotection in the mature male heart through modulation of mitochondrial oxygen consumption and mitochondrial free matrix calcium concentration ([Ca2+]Mito). The efficacy of cardioplegia ± diazoxide in the aged male heart and in the mature and aged female heart was unknown.
Methods: Mature (20 week) and aged (>32 month) male and female rabbit hearts (n=196) were subjected to Langendorff perfusion. Control hearts were perfused for 180 min. Global ischemia (GI) hearts were subjected to 30 min. global ischemia and 120 min. reperfusion. Cardioplegia ± diazoxide was delivered 5 min. prior to global ischemia. Hemodynamics, infarct size, mitochondrial oxygen consumption and [Ca2+]Mito were determined.
Results: GI significantly decreased post-ischemic functional recovery and significantly increased infarct size in male and female hearts (p<0.05 vs. Control) and was associated with significantly decreased mitochondrial oxygen consumption and significantly increased [Ca2+]Mito (p<0.05 vs. Control for each). The effects of GI were exacerbated (p<0.001) in aged hearts. Cardioplegia ± diazoxide significantly increased post-ischemic functional recovery, significantly decreased infarct size and modulated mitochondrial oxygen consumption and [Ca2+]Mito (p<0.05 vs GI for each) in both mature and aged males but this cardioprotection was significantly decreased in mature and aged females (p<0.001 for each).
Conclusion: Tolerance to GI is significantly effected by age but not gender. Cardioplegia ± diazoxide modulates GI and is significantly effected by age and gender. Diazoxide enhances cardioprotection in male but not female hearts. These data demonstrate that currently optimized cardioplegia protocols effective in males are not as efficacious in females, due in part, to differences in mitochondrial oxygen consumption and [Ca2+]Mito.