Quantitative evaluation of relationship between cardiac energy metabolism and post-ischemic recovery of contractile...

Quantitative Evaluation of Relationship between Cardiac Energy Metabolism and Post-ischemic Recovery of Contractile Function. Mechanisms of ischemic damage were studied by defining the relationships between post-ischemic work recovery and tissue ATP levels in isolated rat hearts as well as mitochondrial respiration rates in skinned myofibrils. Pre-ischemic levels of ATP were reduced by 2-deoxyglucose treatment and assessed using 31P-NMR. A 70% fall of ATP was not associated with decreased functional recovery. Mitochondrial respiration was assessed without mitochondrial isolation in skinned cardiac fibers in physiological salt solution using a novel method developed by Veksler et al. Maximal rates of mitochondrial respiration were not changed after 35 min of normothermic ischemia using St. Thomas's Hospital cardioplegic solution followed by 30 min of aerobic reperfusion. Only a reversible increase in the rate of basal respiration and a decrease in creatine-stimulated oxygen uptake were observed. Thus, mitochondrial oxidative phosphorylation, as assessed in skinned myofibrils, was tolerant to an ischemic period which induced permanent depression of contractile function along with alterations in metabolite distribution. As a result, tissue level of ATP and rates of mitochondrial respiration provided an estimate of ischemic damage only in cases where damage reached a very severe extent.