Antiarrhythmic effects of cyclic guanosine 3' :5'-monophosphate and sodium nitroprusside on barium chloride arrhythmias in rabbits.

The hypothesis that c GMP and sodium nitroprusside (NP), an activator of guanylate cyclase which elevates levels of c GMP, have antiarrhythmic activity was tested in the barium chloride (BaCl2) model of arrhythmias. Electrocardiograms were recorded continuously on tape in unanesthetized New Zealand white rabbits weighing approximately 2.0 kg. BaCl2, 4 mg/kg i.v. bolus, induced frequent ventricular ectopic beats. These ventricular arrhythmias were abolished by 8-bromo-c GMP, 5 mg/kg, injected into the left ventricle (5/6 rabbits), NP 25.0 microgram/kg/min i.v. (6/6), NP 10 micrograms/kg/min i.v. (3/6), and markedly reduced in frequency by NP 10 micrograms/kg/min (3/6). In temporal association with NP, 4 fold increases in c GMP levels in blood and significant increases in myocardial GMP were found compared to control animals (n = 6). In this model, c GMP and NP have significant antiarrhythmic properties. NP effect may be mediated by alterations in c GMP metabolism.