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

  • B.C. Wexler
    Affiliations
    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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      Abstract

      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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      References

        • Wexler B.C.
        Pathophysiologic changes induced in arteriosclerotic and nonarteriosclerotic rats by methylandrostenediol.
        Lab. Invest. 1971; 25: 158-168
        • Wexler B.C.
        Spontaneous arteriosclerosis in repeatedly-bred male and female rats.
        J. Atheroscler. Res. 1964; 4: 57-80
        • Wexler B.C.
        • True C.W.
        Carotid and cerebral arteriosclerosis.
        Circ. Res. 1963; 12: 659-666
        • Wexler B.C.
        Spontaneous coronary arteriosclerosis in repeatedly bred male and female rats.
        Circ. Res. 1964; 14: 32-43
        • Wexler B.C.
        Spontaneous arteriosclerosis of the mesenteric, renal and peripheral arteries of repeatedly bred rats.
        Circ. Res. 1964; 15: 485-496
        • Wexler B.C.
        Arteriosclerosis of the renal artery of repeatedly bred male and female rats.
        Atherosclerosis. 1970; 11: 383-400
        • Wexler B.C.
        • Kittinger G.W.
        Myocardial necrosis in rats: serum enzymes, adrenal steroid and histopathological alterations.
        Circ. Res. 1963; 13: 159-171
        • Wexler B.C.
        • Kittinger G.W.
        Steroids produced in vitro by adrenal glands of normal and arteriosclerotic rats during and after drug-induced myocardial necrosis.
        Circ. Res. 1965; 16: 322-331
        • Wexler B.C.
        • Kittinger G.W.
        • Judd J.T.
        Responses to drug-induced myocardial necrosis in rats with various degrees of arteriosclerosis.
        Circ. Res. 1967; 20: 78-87
        • Wexler B.C.
        • Judd J.T.
        • Kittinger G.W.
        Myocardial necrosis induced by isoproterenol in rats: changes in serum protein, lipoprotein, lipids and glucose during active necrosis and repair in arteriosclerotic and non-arteriosclerotic animals.
        Angiology. 1968; 19: 665-682
        • Wexler B.C.
        Serum creatine phosphokinase activity following isoproterenol-induced myocardial infarction in male and female rats with and without arteriosclerosis.
        Ameer. Heart J. 1970; 79: 69-79
        • Wexler B.C.
        Acute serum enzyme and metabolic changes in arteriosclerotic vs. non-arteriosclerotic rats following isoproterenol-induced myocardial infarction.
        Angiology. 1970; 22: 251-261
        • Lutmer R.F.
        • Wexler B.C.
        Myocardial and serum lactate changes during isoproterenolinduced infarction.
        Amer. Heart J. 1971; 81: 516-520
        • Wexler B.C.
        • Judd J.T.
        Acute myocardial histopathology in normal and arteriosclerotic rats during isoproterenol-induced infarction.
        Brit. J. exp. Pathol. 1970; 51: 646-652
        • Judd J.T.
        • Wexler B.C.
        Myocardial connective tissue metabolism in response to injury, Part I (Histologic and chemical studies of mucopolysaccharide and collagen in rats after isoproterenol-induced infarction).
        Circ. Res. 1969; 25: 201-214
        • Judd J.T.
        • Wexler B.C.
        Myocardial connective tissue metabolism in response to injury, Part II (Investigation of the mucopolysaccharides involved in isoproterenol-induced necrosis and repair in rat hearts).
        Circ. Res. 1970; 26: 101-109
        • Saroff J.
        • Wexler B.C.
        Isoproterenol-induced myocardial infarction in rats: distribution of corticosterone.
        Circ. Res. 1970; 27: 1101-1109
        • Kannel W.B.
        • Gordon T.
        • Schwartz M.J.
        Systolic versus diastolic blood pressure and risk of coronary heart disease.
        Amer. J. Cardiol. 1971; 27: 335-346
        • Kannel W.B.
        • Gordon T.
        • Castelli W.P.
        • Margolis J.
        Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease.
        Ann. Intern. Med. 1970; 72: 813-822
        • Frank C.W.
        • Wimblatt E.
        • Shapiro S.
        • Sager R.V.
        Prognosis of men with coronary heart disease as related to blood pressure.
        Circulation. 1968; 38: 432-438
        • Judd J.T.
        • Wexler B.C.
        The role of lactation and weaning in the pathogenesis of arteriosclerosis in female breeder rats.
        J. Atheroscler. Res. 1969; 10: 153-172
        • Kittinger G.W.
        • Wexler B.C.
        Adrenal gland dehydrogenases and corticosteroid production in normal and arteriosclerotic breeder rats.
        in: 13th edition,. Proc. Soc. exp. Biol. Med.118. 1965: 365-367
        • Wexler B.C.
        • Saroff J.
        Divergent responses of arteriosclerotic and non-arteriosclerotic rats to a catabolic dose of cortisone.
        Acta Endocrinol. 1969; 61: 509-524
        • Oliver M.F.
        • Kurien V.A.
        • Greenwood T.W.
        Relation between serum-free-fatty-acids and arrhythmias and death after acute myocardial infarction.
        Lancet. 1968; i: 710-714
        • Opie L.H.
        • Thomas M.
        • Owen P.
        • Norris R.M.
        • Holland J.
        • Noorden S.Van
        Failure of high concentrations of circulating free fatty acids to provoke arrhythmias in experimental myocardial infarction.
        Lancet. 1971; i: 818-822
        • Hood Jr., W.B.
        • Bianco J.
        • Kumar R.
        • Whiting R.B.
        Experimental myocardial infarction, Part IV (Reduction of left ventricular compliance in the healing phase).
        J. Clin. Invest. 1970; 49: 1316-1323
        • Roberts W.C.
        • Cohen L.S.
        Left ventricular papillary muscles: Description of the normal and a survey of conditions causing them to be abnormal.
        Circulation. 1972; 46: 138-154
        • Black-Schaffer B.
        Infantile endocardial fibroelastosis.
        Arch. Pathol. 1957; 63: 281-306
        • Herman G.
        • Haupt G.J.
        • Birkhead N.C.
        Rapid myocardial calcification after cardiac surgery.
        JAMA. 1963; 186: 260-261
        • Somers K.
        • Williams A.W.
        Intracardiac calcification in endomyocardial fibrosis.
        Brit. Heart J. 1962; 24: 324-328
        • Gore I.
        • Arons W.
        Calcification of the myocardium: Pathologic study of thirteen cases.
        Arch. Pathol. 1949; 48: 1-12
        • Woodhouse M.A.
        • Burston J.
        Metastatic calcification of the myocardium.
        J. Pathol. 1969; 97: 773-776
        • Oliver M.F.
        • Samuel E.
        • Morley P.
        • Young G.B.
        • Kapur P.L.
        Detection of coronary artery calcification during life.
        Lancet. 1964; i: 891-895
        • Zeman F.D.
        • Rodstein M.
        Cardiac rupture complicating myocardial infarction in the aged.
        AMA Arch. Int. Med. 1960; 105: 431-443
        • Fierer J.A.
        • Wagner B.M.
        • Strebel R.F.
        Metastatic calcification of the myocardium.
        Amer. J. Cardiol. 1970; 26: 423-426
        • Strebel R.F.
        • Wagner B.M.
        Experimental tissue calcification, Part V (Effect of parathyroidectomy on spontaneously occurring calcific arteriosclerosis in female breeder rats).
        Arch. Pathol. 1969; 87: 93-99
        • Nickerson M.
        • Karo G.W.
        • Dresel P.E.
        Pathogenesis of “electrolyte-steroid-cardiopathy”.
        Circ. Res. 1961; 9: 209-217