Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat.
Cardiac hypertrophy (CH) and hypertension (HT) are major determinants of sudden cardiac death in patients with coronary artery disease. To investigate the hypothesis that CH and HT increase the incidence of severe ventricular arrhythmias in an animal model, we performed a 30-min period of coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto (WKY) and Wistar (W) rats. The incidence and duration of ventricular fibrillation resulting from coronary artery occlusion were significantly (p less than 0.01) increased in hypertensive rats compared to normotensive animals. The calcium entry blocker nicardipine was administered orally to SHR either chronically for 8 weeks (20 mg.kg-1 twice daily) or acutely as a single dose of 20 mg.kg-1. After long-term treatment with nicardipine, left ventricular hypertrophy index and systolic blood pressure were significantly (p less than 0.001) reduced when compared to vehicle-treated SHR, whereas a single administration of nicardipine only decreased blood pressure without affecting cardiac mass. In the long-term nicardipine-treated SHR group, acute coronary artery ligation induced significantly less ventricular fibrillation (p less than 0.05) and mortality (p less than 0.001) than in acutely nicardipine-treated or untreated SHR groups. In conclusion, the data suggest that the severity and incidence of lethal ventricular arrhythmias are more elevated in hypertensive than in normotensive rats and this may be related to the myocardial hypertrophic state.
Bélichard
P
P
Centre de Recherche, Laboratoires Fournier S.A., Dijon, France.
Pruneau
D
D
Rochette
L
L
D000818:Animals; D006332:Cardiomegaly / Q000150:complications*; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy; D006973:Hypertension / Q000150:complications*; D008955:Models, Cardiovascular; D009529:Nicardipine / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014693:Ventricular Fibrillation / Q000209:etiology*
D009529:Nicardipine