Cardiac versus coronary vasodilator actions of KB-944, a new calcium antagonist, assessed in isolated, blood-perfused heart preparations of dogs.
We compared the cardiac and coronary vasodilator actions of a new calcium-antagonistic vasodilator, KB-944, in isolated, blood-perfused heart preparations of dogs. In all preparations KB-944 injected intra-arterially produced an increase in blood flow. In sinoatrial (SA) node preparations KB-944 decreased sinus rate and in large doses produced atrial standstill. In atrioventricular (AV) node preparations KB-944 increased AV conduction time and in large doses produced second- or third-degree AV block only when injected into the artery supplying the AV node. In the same preparations KB-944 had virtually no effect on AV conduction when injected into the artery supplying the His-Purkinje-ventricular system. In papillary muscle preparations KB-944 in medium and large doses depressed force of contraction, the depressant action being greater at high rates of contraction. In the same kind of preparations KB-944 affected automaticity slightly and inconsistently. Depression by KB-944 of SA nodal automaticity and AV nodal conduction occurred pari passu with coronary vasodilation, whereas force of contraction was depressed to a lesser extent in coronary vasodilator doses. In these respects, KB-944 resembles verapamil and diltiazem rather than nifedipine and nicardipine.
D000818:Animals; D052160:Benzothiazoles; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D013844:Thiazoles; D014665:Vasodilator Agents; C035950:fosfedil