Cardioprotection with Captopril added to Bretschneider-Solution: An in vitro rabbit heart study

Objective: Angiotensin-converting enzyme inhibitors have recently been shown to attenuate left ventricular dysfunction after cardioplegic arrest, however, evidence as to how this effect is mediated is scarce.

Methods: Rabbit hearts were perfused using a Langendorff apparatus. The Control group underwent cardioplegia with conventional HTK-Bretschneider solution (n = 6) Whereas the other groups recieved the following adjuncts added to the cardioplegic solution (each n = 6): captopril (100µmol/l), Losartan (100 nmol/l) for selective AT-II receptor type 1 blockade or BQ123 (100 nmol/l) for selective Endothelin-receptor type A blockade. 45 minutes of equilibration were followed by 90 minutes of cardioplegic arrest and 30 minutes of reperfusion. Indices for myocardial contractility, coronary flow, heartrate and O₂-consumption were recorded before and after ischemic arrest. Tissue ATP and malondialdehyde (MDA) contents were measured to evaluate energy content and oxidative stress.

Results: The treatment with Captopril added to the cardioplegic solution improved substantially the recovery of myocardial contractility after arrest (Control vs. Captopril: 5 min P < 0.001, 10 min P = 0.002, 20 min P = 0.002, 30 min P = 0.002) while consuming less oxygen (P = 0.004). Moreover the ATP content of the reperfused tissue was significantly elevated compared with control group (24 ± 2 µmol/g vs. 16 ± 2 µmol/g P = 0.033), whereas the level of MDA was substantially decreased (0,58 ± 0,163 µmol/g vs. 1,5 ± 0,28 µmol/g P = 0.009). This effect could not be reproduced neither by selective ATII-receptor type 1 nor by selective ETA-receptor blockade.

Fig. 1: Development of left ventricular pressure

Conclusions: Adding Captopril to HTK cardioplegia solution leads to a significantly greater and faster recovery of myocardial contractility after prolonged global ischemia and reperfusion, while consuming less oxygen. These effects seem not to be mediated through ATII-receptor type 1 by Angiotensin II nor crossactivation of Endothelin-receptor type A by Endothelin.