RT Journal Article SR Electronic T1 Carrier-Mediated Norepinephrine Release and Reperfusion Arrhythmias Induced by Protracted Ischemia in Isolated Perfused Guinea Pig Hearts: Effect of Presynaptic Modulation by α2-Adrenoceptor in Mild Hypothermic Ischemia JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 681 OP 687 DO 10.1124/jpet.102.036863 VO 303 IS 2 A1 Jun-ichi Oka A1 Michiaki Imamura A1 Eiichiro Hatta A1 Ryushi Maruyama A1 Mitsuhiro Isaka A1 Toshifumi Murashita A1 Keishu Yasuda YR 2002 UL http://jpet.aspetjournals.org/content/303/2/681.abstract AB Yohimbine, an α2-adrenoceptor antagonist, has been reported to protect hypoxic myocardium and inhibit carrier-mediated norepinephrine (NE) release and reperfusion arrhythmias (ventricular fibrillation; VF) in normothermic ischemia. In heart surgery, mild hypothermic (tepid) cardioplegia has been reported to reduce metabolic demand and permit immediate recovery of cardiac function. Therefore, we determined the effect of yohimbine on NE release and reperfusion arrhythmias in isolated perfused guinea pig hearts of tepid temperature (32°C) ischemia model. Stepwise increase of global ischemia period (20, 40, and 60 min) induced a progressive increase of NE release and duration of VF. Neuronal uptake 1 inhibitor desipramine (100 nM) and Na+-H+ exchanger inhibitor 5-N-ethyl-N-isopropyl-amiloride (10 μM) decreased NE and VF in 60-min hypothermic ischemia. This indicated that NE release induced by protracted tepid ischemia was due to carrier-mediated release. Yohimbine (1 μM) markedly reduced NE release and VF (p < 0.01 versus control) and 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine [UK 14,304 (UK); 10 μM], an α2-adrenoceptor agonist, increased NE release and VF (p < 0.01 versus control). Yohimbine (1 μM) prevented the potentiated effect of UK (10 μM) in hypothermia (p < 0.01 versus UK). Our findings indicate that presynaptic reduction of carrier-mediated NE release seems to be one of the most important factors controlling reperfusion arrhythmias, and α2-adrenoceptor blockade by yohimbine (1 μM) in tepid ischemia may contribute to effective myocardial protection in terms of NE release and reperfusion arrhythmia. The American Society for Pharmacology and Experimental Therapeutics