Background-Recent studies have demonstrated that aging is associated with reduced tolerance to ischemia and that the aged (not senescent) female heart has greater susceptibility to ischemia as compared with the aged male heart. Previously, we have shown that ischemia can be modulated with cardioplegia in the male heart; however, efficacy in the female heart was unknown.
Previously, we have shown that the pharmacological opening of the mitochondrial ATP-sensitive K channels with diazoxide (DZX) enhances the cardioprotection afforded by magnesium-supplemented potassium (K/Mg) cardioplegia. To determine the mechanisms involved in the cardioprotection afforded by K/Mg + DZX cardioplegia, rabbit hearts (n=24) were subjected to isolated Langendorff perfusion. Control hearts were perfused for 75 min. Global ischemia (GI) hearts were subjected to 30 min of equilibrium, 30 min of GI, and 15 min of reperfusion. K/Mg and K/Mg + DZX cardioplegia hearts received either K/Mg or K/Mg + DZX for 5 min before GI and reperfusion. Tissue was harvested for mitochondrial isolation and transmission electron microscopy (TEM). Mitochondrial structure, area, matrix volume, free calcium, and oxygen consumption were determined. TEM demonstrated that GI mitochondria were damaged and that K/Mg and K/Mg + DZX preserved mitochondrial structure. TEM and light scattering demonstrated separately that mitochondrial matrix and cristae area and matrix volume were significantly increased after GI and reperfusion with GI > K/Mg + DZX > K/Mg hearts (P <0.05 vs. control). Mitochondrial free calcium was significantly increased in GI and K/Mg hearts. K/Mg + DZX significantly decreased mitochondrial free calcium accumulation (P <0.05 vs. GI and K/Mg). State 3 oxygen consumption and respiratory control index in malate (complex I substrate)- and succinate (complex II substrate)-energized mitochondria were significantly decreased (P <0.05 vs. control) in the GI and K/Mg + DZX groups. These data indicate that the enhanced cardioprotection afforded by K/Mg + DZX cardioplegia occurs through the preservation of mitochondrial structure and the significant decrease in mitochondrial free calcium accumulation and mitochondrial state 3 oxygen consumption.
Background-We have recently shown that the cardioprotection afforded by cardioplegia is affected by age and gender and is less effective in the aged female rabbit heart compared with the aged male rabbit heart. We hypothesized that these differences were due to age and gender-specific modulation of mitochondrial oxygen consumption and mitochondrial free matrix calcium ([Ca 2+ ] Mito ) content occurring during early reperfusion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.