Abstract
Isolated rat hearts were perfused at temperatures from 40 to 30°C in the presence and absence of 16 m m potassium cardioplegia, with hypoxic substrate-free Krebs-Henseleit medium. During hypoxia the development of contracture was monitored with an intraventricular balloon. After intervals from 10 to 300 min of hypoxia hearts were reoxygenated at 37°C and the released creatine kinase activity (CK) was measured for a 15 min interval. At the end of experiments, the percentage of injured cells was estimated by light microscopy. Both hypothermia and cardioplegia delayed the onset and reduced the rate of development of contracture. The effects of cardioplegia and hypothermia were additive. Irreversible injury was delayed proportionally with the delay in full contracture development. Hypothermia caused a progressive decrease in the rate of progression of injury. Cardioplegia also reduced the slopes of injury curves, but its major effect was to delay the onset of injury. Between 40 to 30°C there was a nearly linear decrease in the slopes of injury curves from a rate of 6.6% per min. at 40°C to 0.85% per min. at 30°C. Estimates of injury by CK release and morphology were similar. Severe hypoxic injury was associated with marked reductions in coronary flow rates to about 40% of control flows. In hypoxic hearts at 37°C vascular infusion of colloid carbon demonstrated subendocardial zones of severe ischemia ranging from 10 to 40% of heart ventricular masses. There was no apparent correlation between coronary flow rates and the size of observed perfusion defects. It is concluded that myocardial protection occurs as the combined effect of delaying the onset of injury and slowing its progression after initiation. The proportion of cells in a heart showing morphologic evidence of injury correlated with the observed enzyme release. Injury appeared to progress in quantum steps as individual cells made the transition from reversible to irreversible injury. Reductions in slopes of injury curves with protection could be explained as a slowing of the rate of energy depletion in a heterogenous cell population and a spreading of the time interval over which cells reached a critical level of energy depletion. The existence of perfusion defects and concomitant ischemia may limit the isolated perfused rat heart as an experimental model of hypoxic cell injury.
Published Version
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