Apoptosis Inhibition for improved Left Ventricular Function after prolonged Cold Cardioplegic Arrest

Abstract

Cardioplegic arrest (CA) is associated with myocardial apoptosis induction. Data suggest that apoptosis inhibition during regional myocardial ischemia reduces infarct size and improves regional contractility. 28 adult rats were anesthetized and mechanically ventilated. Hearts were arrested by administration of ice-cold crystalloid cardioplegia (Bretschneider solution, Custodiol®, 10 ml/kg) with and without supplementation of a cell permeable non-selective caspase-inhibitor (z-VAD-fmk, 10 mM, n=7 each). Hearts were stored for 4h and 18h (n = 14 each) in cardioplegia (4°C). Subsequently, hearts were reperfused on a Langendorff-System. A balloon connected to a pressure transducer was inserted in the LV and inflated to a diastolic pressure of 10 mmHg. After 4h of cold CA, hearts with apoptosis-inhibition had higher LV pressures throughout the 60 min reperfusion as compared to those without apoptosis-inhibition. Both positive and negative dp/dtmax were significantly higher with apoptosis inhibition. After 18h cold CA, hearts with apoptosis-inhibition had higher left ventricular pressures throughout 90 min reperfusion as compared to those without apoptosis-inhibition. Dp/dtmax was significantly higher with apoptosis inhibition at 70, 80, and 90 min reperfusion. In hearts with apoptosis-inhibition heart rate recovered markedly faster. Apoptosis-inhibition preserves LV function after prolonged cold CA.