Celiprolol, a Selective .BETA.1-Blocker, Reduces the Infarct Size Through Production of Nitric Oxide in a Rabbit Model of Myocardial Infarction

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Abstract
Background It is still unclear whether celiprolol, a β1-selective blocker, reduces myocardial infarct size. This study will examine whether celiprolol reduces myocardial infarct size, as well as investigate the mechanisms for its infarct size-reducing effect in rabbits. Methods and Results Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Celiprolol (1 or 10 mg · kg -1 · h-1 for 60 min, iv) was administered 20 min before ischemia with or without pretreatment with Nω-nitro-L-arginine methylester (L-NAME, 10 mg/kg, iv, a nitric oxide synthase inhibitor) or 5-hydroxydecanoic acid sodium salt (5-HD, 5 mg/kg, iv, a mitochondrial KATP channel blocker). The area at risk as a percentage of the left ventricle was determined by using Evens blue dye, and the infarct size was determined as a percentage of the area at risk by triphenyl tetrazolium chloride staining. Celiprolol 1 and 10 mg · kg-1 · h-1 significantly reduced the infarct size in a dose-dependent manner (36.4±1.7%, n=7 and 25.4±2.9%, n=7, respectively) compared with the control (46.2±3.1%, n=8). The infarct size-reducing effect of celiprolol was completely blocked by L-NAME (40.4 ±2.8%, n=8) but not by 5-HD (27.3±1.0%, n=8). Celiprolol 1 mg · kg-1 · h -1 increased the myocardial interstitial levels of NOx, an indicator of nitric oxide, and reduced the intensity of dihydroetidium staining of myocardium, an indicator of superoxide, during reperfusion after 30 min of ischemia. Conclusion Celiprolol reduces myocardial infarct size and also increases nitric oxide production and reduces superoxide levels but not mitochondrial KATP channels in rabbits. (Circ J 2007; 71: 574 - 579)

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