Attenuation by R 56865, a novel cytoprotective drug, of regional myocardial ischemia- and reperfusion-induced electrocardiographic disturbances in anesthetized rabbits.

Abstract

We investigated the antiischemic and antiarrhythmic effects of R 56865 in pentobarbital-anesthetized, open-chest rabbits subjected to 10 min regional myocardial ischemia and 20 min reperfusion, using two experimental protocols. In the first, R 56865 (0.02-0.16 mg/kg) was administered as a bolus intravenous (i.v.) injection 5 min before ligation of a branch of the left circumflex coronary artery (LCX); in the second, the drug, at the highest dose studied (0.16 mg/kg), was injected by the same route during ischemia, 5 min after coronary artery ligation. Ischemia-induced ST segment increase and reperfusion-induced ventricular arrhythmias were determined in lead II of the four-limb ECG. Mean carotid arterial pressure and heart rate (HR) were also measured. When given before ischemia, R 56865 dose-dependently prevented ischemia-induced ST segment increase and reperfusion arrhythmias. The antiischemic and antiarrhythmic dose-response curves were superimposable, suggesting a common mechanism of action. R 56865 (0.16 mg/kg) fully attenuated ischemia-induced ST segment shift and ventricular arrhythmias on reperfusion. These protective effects were not associated with systemic hypotension or bradycardia. When high-dose R 56865 (0.16 mg/kg) was given during ischemia, ST segment shift and ventricular arrhythmias on reperfusion were not attenuated. The results strongly suggest that R 56865 affords protection against the deleterious effects of moderate ischemia by mechanisms not associated with an indirect reduction of cardiac work. R 56865 may elicit cardioprotection directly in ischemic tissue.

• Authors: Y Verscheure, G Pouget, F De Courtois, B Le Grand, G W John
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 25 Issue 1 Pg. 126-33 (Jan 1995) ISSN: 0160-2446 [Print] United States
• PMID: 7723341 (Publication Type: Journal Article)

Chemical References

• Benzothiazoles
• Calcium Channel Blockers
• Piperidines
• Thiazoles
• R 56865

Topics

• Analysis of Variance
• Animals
• Arrhythmias, Cardiac (prevention & control)
• Benzothiazoles
• Calcium Channel Blockers (administration & dosage, pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Electrocardiography (drug effects)
• Heart (drug effects)
• Hemodynamics (drug effects)
• Injections, Intravenous
• Male
• Myocardial Ischemia (drug therapy, physiopathology)
• Myocardial Reperfusion Injury (drug therapy, physiopathology)
• Myocardium (cytology)
• Piperidines (administration & dosage, pharmacology, therapeutic use)
• Rabbits
• Random Allocation
• Thiazoles (administration & dosage, pharmacology, therapeutic use)