Noradrenaline reduces ischemia-induced arrhythmia in anesthetized rats: involvement of alpha1-adrenoceptors and mitochondrial K ATP channels.

INTRODUCTION We have evaluated the part played by the mitochondrial ATP-sensitive potassium (mK(ATP)) channels on effect of alpha(1)-adrenoceptor activation by noradrenaline in ischemia-induced ventricular arrhythmia. METHODS AND RESULTS Anesthetized rats were subjected to 25 minutes of regional ischemia, and infarct size (IS) and ischemia-induced ventricular arrhythmia were measured. Group I served as saline control with ischemia (n = 9). In group II (n = 9), the ischemic period was preceded by three short episodes of ischemia, followed by reperfusion. In group III, noradrenaline (2 microg/kg, IV, n = 9) was injected prior to ischemia. In group IV, an alpha(1)-adrenoceptor blocker (prazosin, 0.5 mg/kg, IV, n = 6) was administrated prior to noradrenaline injection. In Groups V and VI, rats received a specific mitochondrial K(ATP) channel inhibitor [5-hydroxydecanoic acid (5-HD), 10 mg/kg, IV, n = 6] prior to or after noradrenaline injection. Ischemic preconditioning (IPC) and noradrenaline markedly reduced incidences of ventricular fibrillation (VF) (0%, 0% vs. 55.5% in control, P < 0.05) and ventricular tachycardia (VT) (11%, 44.5% vs. 100% in control, P < 0.001 and P < 0.05), duration of VF + VT (3 +/- 1 seconds, 4.7 +/- 2.1 seconds vs. 52.9 +/- 6 seconds in control, P < 0.001), number of VF + VT episodes (1.7 +/- 1.7, 5.75 +/- 2.4 vs. 60.5 +/- 8 in control, P < 0.001), severity of arrhythmias (0.3 +/- 0.3, 1.7 +/- 0.5 vs. 3.9 +/- 0.3 in control rats, P < 0.001 and P < 0.01), and IS (13.6 +/- 1.8%, 18.2 +/- 1.5% vs. 49.6 +/- 2.4% in control, P < 0.001). Administration of prazosin or 5-HD prior to or after noradrenaline injection intensified incidences of VF (66.6%, 66.6% and 50%, P < 0.05) and VT (100%, 100%, and 100%, P < 0.05), duration of VF + VT episodes (70.2 +/- 10.5 seconds, 69.8 +/- 6.75 seconds, and 60.8 +/- 14.9 seconds, P < 0.001), number of VF + VT episodes (56 +/- 16.4, 67 +/- 11, and 45 +/- 3.5, P < 0.01, P < 0.001, and P < 0.05), severity of arrhythmias(3.8 +/- 0.3, 4 +/- 0.5, and 3.7 +/- 0.2, P < 0.01, P < 0.05, and P < 0.01), and IS (45.5 +/- 3%, 46.8 +/- 3.4%, and 43 +/- 2.5%, respectively, P < 0.001) compared with the noradrenaline-treated group. CONCLUSION Prazosin or 5-HD treatment eliminated the beneficial effects of noradrenaline on arrhythmogenesis and infarct size.