y-20811 and Tachycardia--Ventricular

During i.v. infusion of rose bengal (48 mg/kg/h), the proximal portion of the rat left coronary artery was illuminated from the outside of the myocardium by green light (540 nm) to produce a transluminal thrombus subsequent to endothelial damages. The primary endothelial damages within the illuminated vascular portion, which resulted from the photochemical reaction between the dye and green light, and the subsequent formation of transluminal platelet-rich thrombus, were easily revealed by both light and electron microscopy. The establishment of the thrombus was accompanied in all cases by the occurrence of ventricular arrhythmias due to myocardial ischaemia. The times required to initiate ventricular premature beats (VPBs) and ventricular tachycardia (VT) were 381 +/- 96 s and 444 +/- 114 s (mean +/- SEM, n = 10), respectively. Pretreatment of the rat with acetylsalicylic acid (3 and 10 mg/kg, i.v.) before the initiation of illumination had no effect on the times required to exhibit the first VPBs and VT, the incidences of both types of arrhythmias were not reduced, and the thrombus was finally formed. On the other hand, pretreatment with Y-20811, a novel thromboxane A2 synthetase inhibitor (0.3, 1 and 3 mg/kg, i.v.), delayed the onset of both VPB and VT in a dose-dependent manner. The incidences of VPBs and VT were significantly reduced at 1 and 3 mg/kg, and the thrombus formation was prevented. The formation of a transluminal thrombus in the left coronary artery by the present technique was highly reproducible and could be functionally evaluated by the occurrence of ventricular arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Aspirin; Coronary Thrombosis; Histocytochemistry; Imidazoles; Male; Myocardium; Photochemistry; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Thromboxane A2; Thromboxane-A Synthase; Ventricular Function