K(ATP) channel opening during ischemia: effects on myocardial noradrenaline release and ventricular arrhythmias

摘要: Cardioprotection by K(ATP) channel openers during ischemia is well documented although ill understood. Proarrhythmic effects may be an important drawback. modulation influences neurotransmitter release in brain synaptosomes. Therefore, we studied the of on myocardial noradrenaline and arrhythmias ischemic rabbit hearts. Isolated hearts were perfused according to Langendorff stimulated. Local electrograms recorded K+-selective electrodes inserted left ventricular free wall. Cromakalim (3 microM) or glibenclamide was added 20 min prior induction global ischemia. After 15, 20, 30 ischemia, reperfused content first 100 ml reperfusate measured. (n = 16) prevented second rise extracellular [K(+)] accordance with its cardioprotective effect. significantly reduced after 15 (mean, 169 +/- SEM 97 pmol/gr dry weight vs. control 941 278; p < 0.05) (230 125 wt 1,460 433; 0.05), but difference no longer significant (cromakalim 2,703 1,195 5,413 1,310; 0.08). Ventricular fibrillation tachycardia occurred 10 13 (77%) 19), six glibenclamide-treated (60%) 15), 14 cromakalim-treated (43%) (p NS). accelerated onset (mean 12.5 1.6 16.2 0.7 min; 0.05). Noradrenaline only early-onset whereas observed without fibrillation. Our results show that activation cromakalim reduces postpones irreversible damage, contributing potential