再灌流不整脈に対するPreconditioningの抑制効果に関する研究
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概要
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Although recent investigations have disclosed that preconditioning limits myocardial infarct size by activating adenosine receptors, it remains unclear how preconditioning modifies reper- fusion arrhythmias. The present study assessed effects of preconditioning on lethal reperfusion ar- rhythmia and examined possible roles of adenosine A? receptor activation, prostanoid production and bradykinin receptor activation in the cardioprotective effect of preconditioning. In an anesthetized open chest rat preparation, reperfusion arrhythmia was induced by 5 min of coronary occlusion and reperfusion with or without preconditioning by 2 min ischemia/5 min reperfusion. Prior to the coro- nary occlusion, rats were given no pharmacological agents, 8-phenyltheophylline (8-PT, lO mg/kg), pertussis toxin (20/μg/kg), aspirin-DL-lysin (18 mg/kg), or Hoe 140 (20 nmol/kg), a bradykinin receptor antagonist. The benefit of 8 PT, pertussis toxin, and Hoe140 was confirmed by the responses to exogenous administration of adenosine, acetylcholine, and bradykinin, respectively. The dose of aspirin-DL-lysin was shown to suppress thromboxane B? production of whole blood ex vivo by more than 90%. The incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) during reperfusion was 100% in the untreated control rats. However, in the preconditioned rats which were given no drug before the preconditioning, VT was observed in only 30% of subjects and no VF was induced (p<0.05 vs. controls by x? test). Pretreatment with 8-PT, pertussis toxin, aspirin-DL-lysin or Hoe 140 did not alter the incidence of VT/VF during reperfusion or significantly block the suppression of the reperfusion arrhythmias by preconditioning. These findings indicate that preconditioning protects the myocardium against reperfusion VT/VF and that A? receptor activation, endogenous prostanoids, and bradykinin receptor activation do not play important roles in the cardioprotective effect of preconditioning against lethal reperfusion arrhythmias in the rat heart.
- 札幌医科大学の論文
- 1992-12-01
札幌医科大学 | 論文
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