1 Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADPribose) polymerase (PARP) is bene®cial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhibition a ords long-term functional bene®t in the reperfused myocardium has not been explored. These questions were addressed in the present study.2 In a rat model of myocardial ischemia (1 h) and reperfusion (up to 24 h), there was a marked and signi®cant activation of PARP in the ischemic borderzone, as determined by poly(ADP-ribose) (PAR) immunohistochemistry. PAR localized to the nuclei of myocytes and in®ltrating mononuclear cells. In the core of the infarction, necrotic tissues and di use PAR staining were observed. PARP activation remained markedly detectable 24 h after reperfusion. The PARP inhibitor 3-aminobenzamide (20 mg kg 71 intraperitoneally 10 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced the activation of the enzyme in myocytes. 3 3-aminobenzamide signi®cantly protected against myocardial morphological and functional alterations at 24 h post-reperfusion. Notably, infarct size was reduced, circulating creatine kinase activity was attenuated, and myocardial contractility (dP dt 71 ) was restored by 3-aminobenzamide. 4 Our results demonstrate a signi®cant and prolonged activation of PARP in the reperfused myocardium, localizing to the necrotic area and the ischaemic borderzone. Furthermore, the studies demonstrate that PARP inhibition a ords long-term bene®cial morphological and functional e ects in the reperfused myocardium. These data strengthen the notion that pharmacological PARP inhibition is a viable novel experimental approach for protection against myocardial reperfusion injury.
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