EFFECT OF CARBACHOL AND CYCLIC-GMP ON SUSCEPTIBILITY TO VENTRICULAR-FIBRILLATION

Reductions in cardiac vagal tone have been shown to correlate with increased susceptibility to ventricular fibrillation (VF). If these reductions in vagal tone contribute to VF, one would predict that interventions that increase vagal tone should protect against these lethal arrhythmias. Therefore, VF was induced in 17 mongrel dogs with healed myocardial infarctions by a 2-min coronary occlusion during exercise. On a subsequent day, the cholinergic agonist carbachol (20 μg/kg, i.v.) was given before the exercise plus ischemia test (n = 14). Carbachol elicited significant reductions in heart rate (control 204.5 ± 27.7 vs. carbachol 147.0 ± 49.6 beats/min) and prevented VF in 11 of 14 animals. When the decline in heart rate was prevented by ventricular pacing, carbachol prevented VF in five of six animals. Cyclic GMP may act as an intracellular messenger of cholinergic activation; therefore, 8-bromo cyclic GMP (n = 9) was infused (100-150 μg·kg-1·min-1, i.v.) throughout the exercise beginning 45 min before onset of exercise. Heart rate increased but VF was prevented in eight of nine animals. Similar results were noted for dibutyryl cyclic GMP (n = 5). These data suggest that cholinergic agonist and cyclic GMP can prevent VF in susceptible animals independently of heart rate changes.