Molsidomine prevents post‐ischaemic ventricular fibrillation in dogs

• Published in: British journal of pharmacology 1986-08, Vol.88 (4), p.779-789
• Main Authors: Cano, Jean‐Paul, Guillen, Jean‐Claude, Jouve, Rémy, Langlet, Francis, Puddu, Paolo‐Emilio, Rolland, Pierre‐Henri, Serradimigni, André
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate; Animals; Antianginal agents. Coronary vasodilator agents; Arrhythmias, Cardiac - drug therapy; Arrhythmias, Cardiac - etiology; Biological and medical sciences; Cardiac Output - drug effects; Cardiovascular system; Coronary Disease - complications; Dogs; Electrocardiography; Heart Rate - drug effects; Heart Ventricles; Medical sciences; Molsidomine; Oxadiazoles - therapeutic use; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Sydnones - therapeutic use; Thromboxane B2 - blood; Vascular Resistance - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1986.tb16250.x

1 Forty anaesthetized dogs were subjected to left circumflex coronary artery ligation followed by reperfusion. Molsidomine was randomly administered to 20 dogs (50 μg kg−1 as an i.v. bolus −15 min prior to coronary occlusion – followed by an infusion of 0.05 μg kg−1 min−1). Standard electrocardiographic leads 2 and 3 were continuously recorded to measure ST segment and ΔR% changes and to document both the number of ventricular premature beats and the onset of ventricular fibrillation; aortic pressure and cardiac output were measured; thromboxane B2 plasma levels, platelet aggregation produced by ADP, and molsidomine plasma levels were determined before and at 10, 30 and 75 min after the start of the drug protocol. 2 Molsidomine protected the treated animals from early (10 min) post‐ischaemic ventricular fibrillation (0 of 20 vs 6 of 20, P = 0.0202), reduced the incidence of overall post‐occlusion ventricular fibrillation (3 of 20 vs 10 of 20, P = 0.0407) and improved the total survival rate (P = 0.0067). 3 In molsidomine treated dogs: mean aortic pressure and the rate‐pressure product were lowered 10 min after the start of the drug; immediate post‐occlusion (3 min) ST segment changes (0.82 ± 0.52 vs 1.52 ± 0.78 mV, P < 0.025) and ΔR% changes (37 ± 50 vs 90 ± 84%, P < 0.025) were less marked; the number of ventricular premature beats was lowered and finally, a progressive decline of platelet aggregation produced by ADP was achieved after 75 min of drug infusion. 4 These results were obtained in the presence of mean plasma levels of molsidomine ranging from 20 to 28 ng ml−1. 5 The time‐action curve of the antifibrillatory effect of molsidomine parallels those at the level of post‐ischaemic electrocardiographic changes.