Cardioplegic effect of Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor against ischemia-reperfusion myocardial injury in cardiac surgery

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kinki University
• Principal Investigator: NISHIWAKI Noboru Kinki University, Hospital, Professor, 医学部附属病院, 教授 (70319739)
• Co-Investigator(Kenkyū-buntansha): KANEDA Kouzou Kinki University, Hospital, Lecturer, 医学部附属病院, 講師 (40340830) ; KOMEDA Masashi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20303810) ; SAJI Yoshiaki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00399776)
• Project Period (FY): 2004 – 2005
• Keywords: Cardioplegia / PARP inhibitor / Ischemia-reperfusion injury / Oxidative stress / 8-OHdG

Research Abstract

Ischemic-reperfusion injury has been one of the most serious problem even in current cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury by preventing energy depletion associated with oxidative stress. The purpose of our study was to evaluate 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.
Isolated rat hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution (St.Thomas 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 cardioplegia, whereas the 3-AB(+) group (n=8) received these solutions supplemented with 3-AB (100 microM). 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.
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.
In conclusion, cardioplegic solution supplemented with PARS inhibitor provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress.