Electrocardiographic analysis of the effects of isosorbide-5-mononitrate on regional myocardial ischemia in conscious dogs.
Whereas the clinical efficacy of isosorbide-5-mononitrate (IS-5-MN) in angina pectoris has been demonstrated unequivocally, the action of the substance on acute myocardial ischemia in animal models has not been investigated yet. Therefore, IS-5-MN and, for comparison in some experiments, isosorbide dinitrate and isosorbide-2-mononitrate were studied on a model of a brief intermittent myocardial ischemia in dogs. Ischemia was produced by occlusion of a coronary artery. Simultaneously, the dogs were loaded by treadmill exercise (model I) or injection of isoprenaline (model II). Local S-T segment changes were derived with epicardial electrodes. The action of orally administered IS-5-MN, isosorbide-2-mononitrate and isosorbide dinitrate of S-T segment elevations was studied with model I. A dose of 20 mg/dog produced a significant lowering of the S-T elevations (17, 13 and 15%). With 40 mg of IS-5-MN and isosorbide dinitrate per dog, similar effects were obtained (18 and 21%, with no statistical significant differences in comparison with 20 mg/dog). The time course of the action of IS-5-MN and the dose-response curve after i.v. injection were evaluated with model II. Even 5 hr after 20 mg of IS-5-MN per dog, a significant reduction of S-T elevations could be demonstrated. Significant effects on the epicardially derived S-T elevations have already been observed at doses of IS-5-MN that do not yet lead to a lowering of the systolic blood pressure in conscious dogs. Higher doses that lower the systolic blood pressure do not lead to any further lowering of the observed S-T elevations.
D000284:Administration, Oral; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D007275:Injections, Intravenous; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D013997:Time Factors
D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate