The effects of nafazatrom on arrhythmias and prostanoid release during coronary artery occlusion and reperfusion in anaesthetized greyhounds.
The effects of the antithrombotic drug nafazatrom (BAY g 6575) were investigated in chloralose-anaesthetized greyhounds subject to coronary artery occlusion and reperfusion. Pretreatment with nafazatrom 10 mg/kg p.o. did not significantly reduce the number of extrasystoles or the incidence of ventricular fibrillation (VF) during the first 30 min occlusion of the left anterior descending coronary artery. However, the incidence of VF resulting from release of a 40-min coronary artery occlusion was markedly reduced (from 88% in the controls to 14% in the nafazatrom group). Both thromboxane B2 (TxB2) and 6-keto PGF1 alpha (breakdown products of TxA2 and prostacyclin respectively) were released from the acutely ischaemic myocardium in control dogs. Nafazatrom did not alter the release of TxB2 but the concentrations of 6-keto PGF1 alpha were elevated in blood draining from both the ischaemic and normal regions of the myocardium. The pronounced anti-fibrillatory effect of nafazatrom during reperfusion of the ischaemic myocardium may be related to the ability of this drug to elevate prostacyclin concentrations in the coronary circulation.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D003327:Coronary Disease / Q000378:metabolism; D004285:Dogs; D011464:Epoprostenol / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D013929:Thromboxane B2 / Q000097:blood
D005343:Fibrinolytic Agents; D011453:Prostaglandins; D011720:Pyrazoles; D047069:Pyrazolones; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; C018845:nafazatrom