Acetylcholine Suppresses Ventricular Arrhythmias and Improves Conduction and Connexin-43 Properties During Myocardial Ischemia in Isolated Rabbit Hearts

Journal of Cardiovascular Electrophysiology
Takeshi AibaMasaru Sugimachi

Abstract

Acetylcholine (ACh), a vagal efferent neurotransmitter, markedly improves survival in rats with myocardial ischemia (MI) by preventing ischemic loss of gap junction (Gj) and by inducing anti-apoptotic cascades. However, electrophysiological mechanisms of the antiarrhythmic effect of ACh after acute MI are still unclear. Acute MI was induced by ligation of the left anterior descending (LAD) coronary artery in Langendorff-perfused rabbit hearts with (ACh(+):n = 11) or without (ACh(-):n = 12) 10 μmol/L ACh delivered continuously starting at 5 minutes before LAD ligation. Action potentials on the left ventricular (LV) anterior surface (≈2×2 cm) were recorded by optical mapping during pacing from the LV epicardium (BCL = 500 milliseconds). Conduction velocities (CVs) at 256 sites were calculated and the ventricular tachycardia/ventricular fibrillation (VT/VF) susceptibility was also assessed by programmed electrical stimulation before and 30 minutes after MI. The amount and distribution of Gj protein connexin-43 was analyzed by immunoblotting and immunohistochemistry. Averaged CV in the ischemic border zone (IBZ) was significantly slower in ACh(-) than in ACh(+) (21 ± 7 vs. 34 ± 6 cm/s; P < 0.01). Short-coupled extra stimulus furthe...Continue Reading

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