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THE JOURNAL OF CARDIOVASCULAR SURGERY
Rivista di Chirurgia Cardiaca, Vascolare e Toracica
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
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ORIGINAL ARTICLES CARDIAC SECTION
The Journal of Cardiovascular Surgery 2003 Febbraio;44(1):37-49
Role of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts
Yamashiro S. 1, Noguchi K. 2, Kuniyoshi Y. 1, Koja K. 1, Sakanashi M. 2
1 2ndDepartment of Surgery School of Medicine, Faculty of Medicine University of the Ryukyus, Nishihara, Okinawa, Japan
2 Department of Pharmacology School of Medicine, Faculty of Medicine University of the Ryukyus, Nishihara, Okinawa, Japan
Aim. It has recently been shown that nitric oxide synthase in the presence of suboptimal levels of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, may favor increased production of oxygen free radicals. This study was designed to define the role of BH4 in myocardial ischemia-reperfusion injury.
Methods. Isolated perfused rat hearts were subjected to 37°C ischemia and reperfusion. Hearts were received with BH4 or vehicle for 5 min just before ischemia and during the first 5 min of the reperfusion period. The effects of BH4 on left ventricular function, myocardial contents of lipid peroxidation and high energy phosphates, and levels of lactate dehydrogenase and nitrite plus nitrate in perfusate before ischemia and after reperfusion were estimated. Moreover, the effect of BH4 given with 2,4-diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of BH4 production, intraperitoneally 24 h before the experiments were estimated.
Results. BH4 improved contractile and metabolic abnormalities in reperfused hearts. Furthermore, BH4 significantly alleviated ischemic contracture during ischemia, and restored diminished perfusate levels of nitrite plus nitrate after reperfusion. On the other hand, DAHP-treatment aggravated ischemia-reperfusion induced functional and metabolic abnormalities. Administration of BH4 improved DAHP-induced functional and metabolic abnormalities.
Conclusion. Results demonstrated that BH4 lessens ischemia-reperfusion injury in isolated perfused rat hearts. Conversely, deficiency of BH4 seems to accelerate endothelial dysfunction and myocardial ischemia-reperfusion injury. Present data may be compatible with the hypothesis that nitric oxide synthase in the presence of insufficiency of BH4 serve as the cause of oxidative injury.