Prevention of myocardial reperfusion injury by poly(ADP-ribose) synthetase inhibitor, 3-aminobenzamide, in cardioplegic solution: in vitro study of isolated rat heart model

Yamazaki, Kazuhiro; Miwa, Senri; Ueda, Kunihiro; Tanaka, Seigo; Toyokuni, Shinya; Unimonh, Oriyanhan; Nishimura, Kazunobu; Komeda, Masashi
August 2004
European Journal of Cardio-Thoracic Surgery;Aug2004, Vol. 26 Issue 2, p270
Academic Journal
Objective: Cardioplegic arrest remains the method of choice for myocardial protection in cardiac surgery. Poly(adenosine 5′-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction by preventing energy depletion associated with oxidative stress. We investigated the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest. Methods: Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n=8) were perfused with a standard cardioplegic solution and terminal warm cardoplegia, whereas the 3-AB(+) group (n=8) received these solutions supplemented with 3-AB (100 μM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis. Results: During reperfusion, the 3-AB(+) group showed significantly higher (P=0.005) dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK; P=0.003, GOT; P<0.001). The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P<0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P=0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group. Conclusion: Cardioplegic solution supplemented with 3-AB provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress and overactivation of PARS.


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