Electrocardiographic analysis of the effects of isosorbide-5-mononitrate on regional myocardial ischemia in conscious dogs.

Abstract

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.

• Authors: K Strein, G Sponer, W Bartsch, B Müller-Beckmann, K Dietmann
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 229 Issue 3 Pg. 787-92 (Jun 1984) ISSN: 0022-3565 [Print] United States
• PMID: 6726657 (Publication Type: Journal Article)

Chemical References

• Isosorbide Dinitrate
• isosorbide-5-mononitrate

Topics

• Administration, Oral
• Animals
• Coronary Disease (drug therapy)
• Disease Models, Animal
• Dogs
• Electrocardiography
• Exercise Test
• Female
• Injections, Intravenous
• Isosorbide Dinitrate (administration & dosage, analogs & derivatives, therapeutic use)
• Male
• Time Factors