Time-dependent changes in canine cardiac mitochondrial function and ultrastructure resulting from coronary occlusion and reperfusion

Abstract

Time-dependent changes in mitochondrial function and structure resulting from 1 hr of left circumflex coronary artery occlusion followed by 2 to 24 hr of reperfusion were examined. These changes were correlated with changes in myocardial ultrastructure, tissue water content, infarct size and mitochondrial calcium content. The heart was removed after different periods of reperfusion, and mitochondria were isolated from ischemic and nonischemic regions of the left ventricle. Tissue samples from ischemic and nonischemic myocardium also were taken for electron microscopy and tissue water content determinations. Infarct size was measured by the nitroblue tetrazolium staining method. Oxygen consumption by mitochondria isolated from ischemic and nonischemic myocardium was measured in vitro. Mitochondria from ischemic myocardium showed time-dependent decreases in rates of oxygen consumption and tightness of coupling. Electron microscopy revealed progressive ultrastructural deterioration in ischemic myocardium, including accumulation of calcium deposits within mitochondria, a finding corroborated by elevated concentrations of calcium in mitochondria isolated from the same area. Tissue wet-to-dry weight ratios were increased significantly in ischemic myocardium. A small, but significant, decrease in respiratory function was observed in mitochondria isolated from nonischemic myocardium several hrs after reperfusion; however, normal respiration was observed 24 hrs after release of occlusion. This latter observation indicates that the nonischemic zone also is affected by regional ischemia. The results obtained indicate that temporary left circumflex artery occlusion and reperfusion result in progressively decreasing mitochondrial function and structure within the ischemic myocardium, and that these changes are accompanied by cellular electrolyte alterations.

Relation between reversal of diastolic creep and recovery of systolic function after ischemic myocardial injury in conscious dogs.

“…'~3 Several mechanisms of prolonged postischemic dysfunction have been proposed, including high energy phosphate depletion, 4 mitochondrial injury, 5 sarcoplasmic reticulum dysfunction, 6 cytosolic calcium influx, 7 contractile protein damage, 8 and myocardial edema. 9 Yet another explanation for postischemic dysfunction may relate to direct interaction between systolic and diastolic abnormalities.…”

Hydrogen peroxide generation by mitochondria isolated from regionally ischemic and nonischemic dog myocardium

“…Our data show that 1 or 2 h of ischemia, with or without reperfusion, alters oxidative phosphorylation parameters in both ischemic and nonischemic hcart regions. Although ischemic conditions and mitochondrial isolation and assay methods differ from study to study, qualitatively similar changes, including those affecting ostensibly nonischemic regions, have been reported before (7,28,33,46,52).…”

Protective Efficacy of Nardostachys jatamansi (Rhizomes) on Mitochondrial Respiration and Lysosomal Hydrolases during Doxorubicin Induced Myocardial Injury in Rats

“…41) Thus decrease in mitochondrial cytochrome content, results in a loss of oxidative phosphorylation capacity. 42) Prior oral administration of N. jatamansi extract retains the cytochrome content at significantly near normal condition. The antioxidant activity 21) as well as the free radical scavenging activity 18) of the phytochemical constituents present in N. jatamansi extract might have been responsible for the maintenance of electron transport chain.…”