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Eur J Cardiothorac Surg 2004;26:270-275
© 2004 Elsevier Science NL

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

^a Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-machi, Sakyo-ku, 606-8507, Kyoto, Japan
^b Laboratory of Molecular Clinical Chemistry, Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan
^c Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Received 15 September 2003; received in revised form 12 March 2004; accepted 6 April 2004.

^* Corresponding author. Tel.: +81-75-751-3780, fax: +81-75-751-4960
e-mail: masakom{at}kuhp.kyoto-u.ac.jp

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.

Key Words: Myocardial protection • Cardioplegia • PARS [Poly(ADP-ribose) synthetase] inhibitor • Ischemic reperfusion injury • Heart surgery • Reactive oxygen species (ROS)