Epoprostenol (PGI2) prevents postischemic ventricular fibrillation and improves outcome in a canine model of sudden death

Abstract

In a left circumflex coronary artery occlusion-reperfusion canine model of sudden death the hemodynamic, antiplatelet, antiischemic and antifibrillatory activities of 100 ng.kg-1.min-1 infusion of epoprostenol (Prostacyclin, Flolan, Wellcome Foundation, London, UK) were investigated at random in 40 animals. Significant changes were observed on epoprostenol infusion for mean arterial blood pressure (80 +/- 4 vs 93 +/- 7 mmHg, p less than 0.01), systemic vascular resistance (2379 +/- 769 vs 3290 +/- 768 dynes.s.cm-5, p less than 0.01) and rate-pressure product (10800 +/- 1200 vs 13450 +/- 2500 mmHg.beat.min-1, p less than 0.01) while heart rate did not change. In addition platelet aggregation intensity to ADP decreased by 50% (p less than 0.001). On occlusion treated animals presented with lower systemic vascular resistance (3132 +/- 895 vs 4931 +/- 1079 dynes.s.cm-5, p less than 0.05), rate-pressure product (9950 +/- 850 vs 12168 +/- 1980 mmHg.beat.min-1, p less than 0.01) and mean heart rate (145 +/- 10 vs 169 +/- 10 beats.min-1, p less than 0.01) while the anti-platelet activity persisted. A lower D2-3 mean ST segment elevation occurred at 3 min postocclusion in epoprostenol treated dogs (7.7 +/- 5 vs 14 +/- 8.7 mm, p less than 0.02). The incidence of postischemic ventricular fibrillation was significantly reduced (5/20 i.e. 25% vs 12/20 i.e. 60%, p less than 0.05) in the epoprostenol treated dogs. At the end of the occlusion-reperfusion period treated animals showed an improvement of outcome (10/20 i.e. 50% vs 2/20 i.e. 10%, p less than 0.01). It is suggested that the hemodynamic effect of the drug may provide guidelines for the clinical management of patients with acute myocardial ischemia, when a concomitant antiarrhythmic effect is looked for.