Postinfarction survival and inducibility of ventricular arrhythmias in the spontaneously hypertensive rat : effects of ramipril and hydralazine.
BACKGROUND
Hypertensive patients with left ventricular hypertrophy (LVH) have been found to have greater peri-infarction and postinfarction mortality. In this study, we evaluated the postinfarction survival, susceptibility to ventricular arrhythmias, and degree of LVH and cardiac fibrosis in the spontaneously hypertensive rat (SHR) and the effects of the ACE inhibitor ramipril and the direct vasodilator hydralazine on these characteristics.


RESULTS
An acute myocardial infarction (MI) was produced by ligation of the left anterior descending coronary artery. Rats were randomized to either control (n=50), hydralazine (n=41), or ramipril (n=45). Treatments were started 4 hours after infarction and continued for 8 weeks. Ramipril and hydralazine reduced arterial pressure similarly. Medications were stopped 72 hours before euthanasia, at which time hemodynamic, programmed electrophysiological stimulation (PES), and morphological studies were performed. Mortality was decreased in ramipril (56%) compared with hydralazine (78%) and control (82%) SHRs (P=0.008). This was accompanied by a decrease in myocardial hypertrophy and fibrosis and a decrease in inducibility of ventricular arrhythmias by PES in the ramipril group regardless of MI size. Treatment with hydralazine had little or no effect on LVH and cardiac fibrosis and did not modify inducibility of ventricular arrhythmias by PES. Ramipril but not hydralazine prevented the increase in LV end-diastolic pressure in rats with large MIs.


CONCLUSIONS
In the SHR, the ACE inhibitor ramipril reduces LVH, cardiac fibrosis, and susceptibility to ventricular arrhythmias by PES and improves survival and LV function. Despite a similar decrease in arterial pressure, hydralazine does not have these beneficial effects.
Nguyen
T
T
Department of Medicine and Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
El Salibi
E
E
Rouleau
J L
JL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D016019:Survival Analysis; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D006830:Hydralazine; D017257:Ramipril