Pathophysiologic effects of pre-existing hypertension on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats

  • B.C. Wexler
    May Institute for Medical Research of the Jewish Hospital and Departments of Medicine and Pathology, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229 U.S.A.
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      Male and female, normotensive, virgin Sprague-Dawley rats free of cardiac or vascular complications and male and female, Sprague-Dawley, repeatedly-bred rats having naturally-occurring arteriosclerosis and (mild) hypertension were subjected to unilateral nephrectomy, given 1 % saline drinking water and chronic injections of methylandrostenediol (MAD). In 8 weeks, all of the animals were severely hypertensive. These animals, along with suitable controls, were then subjected to acute and massive myocardial infarction by administration of two, subcutaneous injections of the potent beta adrenergic stimulating agent, isoproterenol. Animals were sacrificed at selected time intervals during the acute phases of myocardial ischemia, necrosis and subsequent repair, Days 1 through 21.
      Mortality was high due to the induction of severe hypertension and was greatly exacerbated with the acute onset of myocardial ischemia, particularly in the breeder rats having a prior history of arteriosclerosis and hypertension. Serum enzyme levels, CPK, SGOT, SGPT and LDH, were greatly elevated during the myocardial ischemia and necrosis phase (Days 1 to 3) as were lipids (i.e., triglycerides, free fatty acids and cholesterol), glucose and BUN. During the repair phase (Days 3 to 21) these physiologic parameters returned to near normal levels. Although most of the animals affected good repair and resolution of their massive cardiac infarcts, subjects with severe hypertension (MAD) developed large, protuberant and saccular left-ventricular aneurysms. Virgin rats with severe hypertension but without significant vascular disease survived. Breeder rats with arteriosclerosis + severe hypertension all died within 7 days post-infarction. These findings demonstrate that pre-existing, severe hypertension plays a key role in the pathogenesis of left-ventricular aneurysm formation following acute myocardial infarction in rats and that severe hypertension combined with arteriosclerosis portends a poor prognosis toward survival.


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