Inhibitory effect of CV4151, a thromboxane A2 synthetase inhibitor, on ventricular arrhythmias induced by coronary artery occlusion in rats.
The purpose of this study was to determine whether thromboxane A2 (TXA2) is involved in the development of ventricular arrhythmias produced by coronary artery occlusion. Ventricular arrhythmias were induced by coronary artery occlusion in 66 male Sprague-Dawley rats. Rats were separated into 4 groups, and saline (n = 19) or CV4151 (a TXA2 synthetase inhibitor)(10 mg/kg, n = 14; 30 mg/kg, n = 15; or 100 mg/kg, n = 18) was injected intravenously 5 min before coronary artery occlusion. The antiarrhythmic effect of CV4151 was assessed in terms of the number of ventricular premature complexes (VPCs), the combined duration of ventricular tachycardia (VT) and ventricular fibrillation (Vf), the incidence of Vf, and the mortality rate within 30 min after occlusion. The total number of VPCs was as follows; control: 1789 +/- 330 beats: 10 mg/kg group: 1289 +/- 302 beats: 30 mg/kg group: 1008 +/- 229 beats: 100 mg/kg group: 986 +/- 275 beats, with no significant differences between groups. The incidence of Vf was significantly reduced in the 30 mg/kg and 100 mg/kg groups, as was the combined duration of VT and Vf and the mortality rate. Our results indicate that the TXA2 synthetase inhibitor CV4151 reduces the incidence of lethal arrhythmias induced by coronary artery occlusion in rats.
Umetani
K
K
Second Department of Internal Medicine, Yamanashi Medical University, Japan.
Tamura
K
K
Komori
S
S
Watanabe
A
A
Ishihara
T
T
Mochizuki
S
S
Li
B
B
Ijiri
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D003327:Coronary Disease / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D008297:Male; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D011725:Pyridines; D013930:Thromboxane-A Synthase; C045446:isbogrel