Total adenine nucleotide stores and sarcoplasmic reticular Ca transport in ischemic rat heart

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Abstract
The relation between the contractility and metabolic changes in reperfusion after ischemia, and the effect of diltiazem on these changes was studied in an isolated rat heart perfused using the Langendorff method. After aerobic perfusion at 80 cmH2O, the perfusion pressure was reduced to 10 cmH2O to induce global ischemia. Substrate was removed from the perfusate during ischemia. After 30 or 60 min of ischemia the heart was reperfused in an aerobic condition. During ischemia the total adenine nucleotide level (TAN: sum of ATP, ADP and AMP) was progressively reduced and the ATP-to-ADP ratio was 1/3 of the value obtained in an aerobic condition. With 30 min of subsequent reperfusion, ATP increased, and the shorter the duration of ischemia, the closer ATP/ADP approached the value of an aerobic condition, whereas TAN was equivalent to the value shown immediately before reperfusion. The degree of ATP recovery by reperfusion mainly depends on the amount of TAN immediately before reperfusion and the mitochondrial function of oxidative phosphorylation that determines ATP/ADP. The Ca transport activity of the sarcoplasmic reticulum of myocardial cells was affected by ischemia and showed no amelioration or further deterioration by subsequent reperfusion. When diltiazem (10-5 M) was added to the perfusate continuously from 5 min before ischemia, during ischemia, and until 10 min of reperfusion, the amount of TAN in ischemia and reperfusion and the Ca transport activity during reperfusion were maintained at relatively high levels. The degree of contractility recovery by reperfusion showed direct correlations with both the tissue ATP amount and the level of Ca transport activity in the sarcoplasmic reticulum.