Suppression of ventricular arrhythmias after coronary artery ligation by pinacidil, a vasodilator drug.
Pinacidil, a new vasodilator compound, has been shown to lower blood pressure in animals and humans by a direct vasodilator effect. We have studied the effects of pinacidil on experimental cardiac arrhythmias in dogs. Pinacidil did not exhibit antiarrhythmic activity on ouabain-induced arrhythmias. In contrast, verapamil had minor antiarrhythmic activity on the ouabain arrhythmia, restoring sinus rhythm in one-third of the dogs studied. Pinacidil suppressed the arrhythmia present 22-24 h after coronary artery ligation at doses which produced a significant reduction in mean arterial pressure. The antiarrhythmic action of pinacidil was not modified by pretreatment with propranolol but appeared to be blunted by the infusion of the alpha-agonist, phenylephrine. Other hypotensive agents, hydralazine and sodium nitroprusside, although producing similar reductions in mean arterial pressure to pinacidil, did not exhibit a consistent antiarrhythmic action in dogs 22-24 h after coronary artery ligation. The calcium antagonist verapamil did not display antiarrhythmic activity on this model. The mechanisms by which pinacidil exerted an antiarrhythmic action have not yet been elucidated. The results of the present study suggest that further studies with pinacidil on myocardial infarct size, myocardial perfusion, and experimental cardiac arrhythmias would be advantageous.
M J
MJ
Kerr
R
R
Wilson
R G
RG
Shanks
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006830:Hydralazine / Q000494:pharmacology; D008026:Ligation; D009599:Nitroprusside / Q000494:pharmacology; D010042:Ouabain / Q000633:toxicity; D010656:Phenylephrine / Q000494:pharmacology; D020110:Pinacidil; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D006830:Hydralazine; D010042:Ouabain; D020110:Pinacidil; D014700:Verapamil