Coronary vasodilator compared to cardiac effects of PY 108-068, a new dihydropyridine vasodilator, on isolated, blood-perfused dog-heart preparations.
We evaluated coronary vasodilator and cardiac effects of PY 108-068 on isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PY 108-068 was administered intra-arterially (i.a.). PY 108-068 increased (coronary) blood flow in all preparations. In SA node preparations, the drug produced a decrease in sinus rate and, in large doses, atrial standstill. In AV node preparations, the drug produced an increase in AV conduction time. Large doses caused second- or third-degree AV block, but only when injected into the artery supplying the AV node. The doses producing a 15% (nearly half maximum) decrease in sinus rate or a 15% (nearly half maximum) increase in AV conduction time were two to three times the doses that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose required to reduce the force of contraction of the papillary muscle by 50% was about 30 times the dose that doubled coronary blood flow. The drug was entirely ineffective on rate of ventricular automaticity. We conclude that PY 108-068 is not likely to produce reflex tachycardia when administered systemically in coronary vasodilator doses.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D009543:Nifedipine; C034600:darodipine