Effects of Coronary Artery Occlusion in Animals with Hypertension and Left Ventricular Hypertrophy

Chronic arterial hypertension (HT) and left ventricular hypertrophy (LVH) increase the morbidity and mortality of acute myocardial infarction in patients. In this article, we discuss earlier studies from Koyanagi et al. in our laboratory that showed that when animals with chronic HT and LVH (HT-LVH) were subjected to acute coronary artery occlusion (CAO), there was a 3.5-fold increase in mortality and a 35% increase in infarct size expressed as a percent of the area at risk. We subsequently determined the effect of HT-LVH on the wavefront of myocardial infarction. Dogs were made hypertensive using a single-kidney, single-clip model of renovascular hypertension that produced mean arterial blood pressure (BP) = 141 ± 3 mm Hg and left ventricular:body weight = 5.8 ± 0.1 g/kg (p < 0.05 vs. control animals). Conscious animals with HT-LVH and control animals were subjected to I or 3 h of CAO. Infarct and risk areas were measured using triphenyltetrazolium chloride (TTC) stain and barium angiography, respectively. The results suggested that the wavefront of infarction was accelerated in animals with HT-LVH. Further studies suggested that the wavefront of myocardial infarction could be markedly retarded by normalizing blood pressure (nitroprusside) l h following CAO. Recent studies in an animal model of HT-LVH suggested that electrophysiological abnormalities occur when these animals were subjected to CAO. Sixty-five percent of animals with HT-LVH had sudden death during CAO compared to 27% of the control group. We studied whether chronic β-adrenergic blockade would reduce mortality associated with CAO in animals with HT-LVH. Dogs were treated with either metoprolol or enalapril to reduce mean arterial BP to approximately 120 mm Hg. Animals with HT-LVH + metoprolol and HT-LVH ± enalapril had sudden death rates of 17 and 53%, respectively; thus, metoprolol decreased the mortality following CAO but enalapril did not. We concluded that the excessive increase in early mortality occurring when dogs with HT-LVH undergo CAO is interrupted with β-blockade possibly via electrophysiological effects rather than changes in arterial pressure or its infarct size. In summary, following CAO, animals with HT-LVH have increased mortality, increased infarct size, and an accelerated wavefront of infarction. The increase in the wavefront of infarction can be retarded by normalizing BP within l h following CAO. The increased mortality can be markedly attenuated if animals are pretreate