Prostacyclin--antiarrhythmic or arrhythmogenic? Comparison of the effects of intravenous and intracoronary prostacyclin and ZK36374 during coronary artery occlusion and reperfusion in anaesthetised greyhounds.

The effects of prostacyclin and ZK36374, a more stable analogue of prostacyclin, were examined in greyhounds anaesthetised with chloralose. Intravenous drug administration (100 ng kg-1 min-1) exacergbated the arrhythmias induced by occlusion of the left anterior descending coronary artery. The incidence of ventricular fibrillation (VF) was 50% in both drug groups compared with 10% in controls. An antiarrhythmic effect was observed when a lower dose (5 ng kg-1 min-1) was infused directly into the coronary circulation. The number of extrasystoles occurring during the first 30 min of occlusion was reduced from 720 +/- 136 in the controls to 327 +/- 167 in the prostacyclin group and 309 +/- 110 (p less than 0.05) in the dogs receiving ZK36374. The only haemodynamic change observed in the dogs receiving intracoronary drug infusions was a small decrease in systemic arterial blood pressure. In the intravenous groups systemic hypotension was accompanied by tachycardia, suggesting that there may have been a reflex increase in sympathetic drive. Increased catecholamine release could account for the higher incidence of VF in the dogs treated with intravenous prostacyclin or ZK36374. The intracoronary administration of both drugs markedly reduced the incidence of VF induced by the release of a 40-min coronary artery occlusion. This latter result suggests that the release of endogenous prostacyclin may have protective effects during reperfusion of the ischaemic myocardium.