PT - JOURNAL ARTICLE AU - Jun-ichi Oka AU - Michiaki Imamura AU - Eiichiro Hatta AU - Ryushi Maruyama AU - Mitsuhiro Isaka AU - Toshifumi Murashita AU - Keishu Yasuda TI - Carrier-Mediated Norepinephrine Release and Reperfusion Arrhythmias Induced by Protracted Ischemia in Isolated Perfused Guinea Pig Hearts: Effect of Presynaptic Modulation by α<sub>2</sub>-Adrenoceptor in Mild Hypothermic Ischemia AID - 10.1124/jpet.102.036863 DP - 2002 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 681--687 VI - 303 IP - 2 4099 - http://jpet.aspetjournals.org/content/303/2/681.short 4100 - http://jpet.aspetjournals.org/content/303/2/681.full SO - J Pharmacol Exp Ther2002 Nov 01; 303 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 &lt; 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 &lt; 0.01 versus control). Yohimbine (1 μM) prevented the potentiated effect of UK (10 μM) in hypothermia (p &lt; 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