Effects of cariporide (HOE642) on myocardial infarct size and ventricular arrhythmias in a rat ischemia/reperfusion model: comparison with other drugs.
The effects of pretreatment with cariporide on myocardial infarction and ventricular arrhythmias in a rat model of ischemia/reperfusion were compared with those of nicorandil, propranolol, and nifedipine. Each drug was administered intravenously before coronary occlusion. Cariporide at 0.1, 0.3, and 1 mg/kg significantly reduced the infarct size (infarct mass/risk mass) from 28 +/- 4% (vehicle control value) to 9 +/- 3, 9 +/- 3, and 5 +/- 2%, respectively. Propranolol at 2.5 mg/kg also significantly reduced the infarct size to 11 +/- 1%. Neither nicorandil nor nifedipine was effective when given at 0.1 mg/kg. Cariporide dose dependently decreased the number of ischemia-induced ventricular premature beats (VPB), incidence and duration of ventricular tachycardia, and the number of reperfusion-induced VPB. Nicorandil was effective against only VPB after reperfusion, and propranolol reduced only postischemic arrhythmias, but nifedipine had no effect on either type of arrhythmia. In summary, cariporide reduced the infarct size and dose dependently suppressed arrhythmias induced by ischemia/reperfusion in rats. In contrast, in the present rat model, the doses of the other three drugs used in this study did not show comparable effects.
Wajima
Teruaki
T
Laboratory of Pharmacology, Aventis Pharma Ltd, Kawagoe, Japan. teruaki.wajima@aventis.com
Beguier
Beatrice
B
Yaguchi
Masafumi
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D020108:Nicorandil / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; D020108:Nicorandil; C093373:cariporide; D011433:Propranolol; D009543:Nifedipine