Evidence as to how
ACE inhibitors attenuate
ischemia-reperfusion injury (IR) after cardioplegic arrest remains scarce. Twenty-four rabbit hearts were perfused on a Langendorff apparatus. Control hearts (n = 6) were arrested with pure
histidine-
tryptophan-ketoglutarate (HTK)-Bretschneider. Treatment groups received added to the
cardioplegic solution (n = 6)
captopril (100 μmol/l) and
losartan (100 μmol/l) for selective AT1-receptor antagonism or
BQ123 (100 nmol/l) for selective ETA-receptor antagonism. Pre-ischemic equilibration of 45 min was followed by 90 min of cardioplegic arrest and 30 min of reperfusion. Indices of myocardial contractility (LVP, dp/dt max, dp/dt min), coronary flow, heart rate, and O2 consumption were recorded before and after ischemic arrest. Tissue
adenosine triphosphate (
ATP) and
malondialdehyde (MDA) contents were measured to evaluate energy content and oxidative stress, respectively. After selective
cardiac arrest with Bretschneider,
captopril-treated hearts showed improved hemodynamics compared to control and the other treatment groups. Oxygen consumption was significantly decreased during early reperfusion in
captopril-treated hearts (34 ± 3 μmol/min/g/mmHg) compared to controls and
losartan- and BQ123-treated hearts (controls: 77 ± 9 μmol/min/g/mmHg, p = 0.003;
losartan: 54 ± 9 μmol/min/g/mmHg, p = 0.015;
BQ123: 64 ± 13 μmol/min/g/mmHg, p = 0.046). The
ATP content of the reperfused tissue was significantly elevated after
captopril treatment compared to control group (24 ± 2 vs. 16 ± 2 μmol/g, p = 0.033), whereas the level of MDA was substantially decreased (0.58 ± 0.163 vs. 1.5 ± 0.28 μmol/g, p = 0.009). ACE inhibition leads to a significantly greater and faster recovery of myocardial contractility after prolonged
cardiac arrest with
Bretschneider solution. Due to decreased oxygen consumption, myocardial protection is enhanced. The association between ACE and
ischemia cannot be clarified by selective blockade of
angiotensin-II receptor type 1 (AT1-R) or ETa receptor (ETa-R).