A comparison of the effects of a series of anti-anginal agents in a novel canine model of transient myocardial ischaemia.
1. An anaesthetized canine model of transient myocardial ischemia (TMI) has been developed in which reproducible and reversible electrocardiographic (ECG) and haemodynamic responses are exacerbated by electrical pacing. 2. The model could separate the ECG and haemodynamic effects of compounds with anti-ischaemic properties. 3. Compounds known to possess peripheral or coronary vasodilator properties did not necessarily alleviate the ECG consequences of TMI since glyceryl trinitrate was active whereas dipyridamole was not. The effects of verapamil were complicated by its adverse conduction effects while lidoflazine inhibited the ECG changes only during the ischaemic phase and the 'metabolic modulator' oxfenicine worsened the ECG response. 4. In a model considered to lack coronary reserve, improvements observed in the ischaemic ECG and global ventricular function were considered to result from a direct myocardial effect of the drugs examined rather than by a vascular influence. This was provided to the greatest degree by the Ca2+-entry blockers nifedipine and nicardipine, with flunarizine adopting an intermediate position.
Allely
M C
MC
Department of Pharmacology, Syntex Research Centre, Riccarton Edinburgh, Scotland.
Alps
B J
BJ
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male
D002316:Cardiotonic Agents