Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

Abstract

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.

Characterization of the hyperpolarization‐activated current, I(f), in ventricular myocytes isolated from hypertensive rats.

“…(DiFrancesco et al 1986;Frace et al 1992) and subsidiary pacemaker cells (DiFrancesco, 1982;Zhou & Lipsius, 1992 (DiFrancesco, 1993) in that it is typically activated upon hyperpolarization, being fully activated at -120 mV; it is caesium and barium insensitive, and has a reversal potential consistent with selectivity for Na+ and K+ (DiFrancesco, 1981b;DiFrancesco et at. 1986;Ho, Brown & Noble, 1994 may play a major role: it might be speculated that it contributes to an increased propensity of the hypertrophied heart for arrhythmias, as observed experimentally (Belichard, Pruneau & Rochette, 1988;Pahor et al 1989;Barbieri et at. 1994) and clinically (McLenachan, Henderson, Morris & Dargie, 1987).…”

Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.

“…1 Furthermore, coronary artery ligation in SHR increases significantly the duration of VF. 2 The propensity of SHR to develop spontaneous or induced arrhythmias is greater in older animals and appears to be related to the duration of hypertension. In fact, an increased incidence of spontaneous, reperfusionand programmed electrical stimulation (PES)-induced VA was observed in previous experiments in isolated hearts from 14-month-old SHR in comparison with hearts isolated from age-matched WKY rats or from 3-month-old SHR.…”

Impacts of Systemic Hypertension and Left Ventricular Hypertrophy on Outcome of Cardiopulmonary Resuscitation and Therapeutic Hypothermia in a Cardiac Arrest Model of Rat

“…SHR was used because it is considered a good animal model of human essential or primary hypertension and has been extensively used to study cardiovascular disease among the experimental hypertension animal models that have been developed to mimic hypertensive responses observed in humans (27,28). The major findings can be summarized as follows: although CPP was significantly higher for SHR during CPR, no differences in resuscitability were observed compared with WKY; hypertensive animals with LVH had a poor neurological outcome compared with normotensive controls under normothermia; a short duration of post-resuscitation mild hypothermia did not improve neurological outcome and survival of SHR.…”