ATTENUATION OF EPINEPHRINE-INDUCED DYSRHYTHMIAS BY BRADYKININ - ROLE OF NITRIC-OXIDE AND PROSTAGLANDINS

Cardiac dysrhythmias are common during anesthesia and surgery. An impo rtant precipitating factor of clinically relevant arrhythmias is the i ntraoperative use of epinephrine. Bradykinin acts as an endogenous car dioprotective substance because it suppresses ventricular dysrhythmias induced by ischemia. In this study, we investigated whether bradykini n has a protective effect, preventing the development of dysrhythmias after epinephrine infusion in rats. Because kinins are potent stimulat ors of the release of nitric oxide and prostaglandins from the endothe lium, we investigated whether the protective effect of bradykinin is m ediated by these 2 autacoids. Male Sprague-Dawley rats anesthetized wi th sodium pentobarbital had catheters placed into a carotid artery and both jugular veins. Arterial blood pressure and lead II of the electr ocardiogram (ECG) were continuously monitored and recorded. After a st eady state was achieved, 1 mg/kg enalapril, an inhibitor of angiotensi n I-converting enzyme/kininase II, was given intravenously to all grou ps except the one treated with losartan. Bradykinin was infused at the initial rate of 0.5 mu g/kg per min. Cardiac arrhythmia was induced w ith 7.5 mu g/kg epinephrine intravenously. Dysrhythmia was assessed by counting the number of premature ventricular contractions (PVCs), run s of ventricular tachycardia (V Tach), and missing Beats during the fi rst minute after epinephrine. In untreated, control rats, epinephrine caused 10.8 +/- 2.7 PVCs, 0.8 +/- 0.2 runs of V tach, and 11.6 +/- 7.4 missing beats/min. In rats pretreated with bradykinin, the same dose of epinephrine elicited 1.2 +/- 0.5 PVCs, no runs of V tach, and 0.4 /- 0.4 missing beats/min. This beneficial effect of bradykinin was par tially reversed by N-nitro-L-arginine methyl ester (L-NAME) or indomet hacin, and completely by L-NAME plus indomethacin or icatibant but it was not affected by des-Arg(9)[Leu(8)]-bradykinin. We conclude that br adykinin, acting on the B-2 receptor, attenuates epinephrine-induced d ysrhythmia via a mechanism that involves the release of NO and prostag landins. Although the mechanism is not clear, NO and prostaglandins ma y prevent epinephrine-induced dysrhythmia and protect the myocardium v ia a direct action on cardiac neurons. (C) 1997 by Excerpta Medica, In c.