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. 1989 May;134(5):1159–1166.

Cardiac pathology in the hypertensive diabetic rat. Biventricular damage with right ventricular predominance.

F S Fein 1, S Cho 1, B E Zola 1, B Miller 1, S M Factor 1
PMCID: PMC1879898  PMID: 2719080

Abstract

The hypertensive-diabetic rat is a new small animal model of cardiomyopathy characterized by ventricular damage. To determine the extent of pathology in this model, quantitation of light microscopic changes in hearts from 15 hypertensive-diabetic rats and 15 age-matched controls was performed. The fraction of myocardium involved by interstitial fibrosis, myocyte necrosis, replacement fibrosis, vascular sclerosis and perivascular fibrosis was computed separately for right and left ventricles. Spontaneously dying as well as deliberately killed hypertensive-diabetic rats were studied. Spontaneously dying animals had higher systolic blood pressures compared with rats killed deliberately. Body weights were lower and lung weights higher in the former group. Left and right ventricular necrosis and fibrosis were increased in spontaneously dying compared with deliberately killed rats. The degree of right ventricular necrosis and fibrosis paralleled that in the left ventricle, but was, unexpectedly, several times greater in magnitude. Thus, quantitative histology in the hypertensive-diabetic rat reveals more cardiac necrosis and fibrosis, in either ventricle, from spontaneously dying animals compared with deliberately killed rats. This damage, coupled with major functional alterations in the viable myocardium, may lead to congestive heart failure or arrhythmia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anversa P., Beghi C., Kikkawa Y., Olivetti G. Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth. Circ Res. 1986 Jan;58(1):26–37. doi: 10.1161/01.res.58.1.26. [DOI] [PubMed] [Google Scholar]
  2. Atkins J. M., Mitchell H. C., Pettinger W. A. Increased pulmonary vascular resistance with systemic hypertension. Effect of minoxidil and other antihypertensive agents. Am J Cardiol. 1977 May 26;39(6):802–807. doi: 10.1016/s0002-9149(77)80030-1. [DOI] [PubMed] [Google Scholar]
  3. Baandrup U., Ledet T., Rasch R. Experimental diabetic cardiopathy preventable by insulin treatment. Lab Invest. 1981 Aug;45(2):169–173. [PubMed] [Google Scholar]
  4. Buccino R. A., Harris E., Spann J. F., Jr, Sonnenblick E. H. Response of myocardial connective tissue to development of experimental hypertrophy. Am J Physiol. 1969 Feb;216(2):425–428. doi: 10.1152/ajplegacy.1969.216.2.425. [DOI] [PubMed] [Google Scholar]
  5. Cohen-Gould L., Robinson T. F., Factor S. M. Intrinsic connective tissue abnormalities in the heart muscle of cardiomyopathic Syrian hamsters. Am J Pathol. 1987 May;127(2):327–334. [PMC free article] [PubMed] [Google Scholar]
  6. Dillmann W. H. Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes. 1980 Jul;29(7):579–582. doi: 10.2337/diab.29.7.579. [DOI] [PubMed] [Google Scholar]
  7. Factor S. M., Bhan R., Minase T., Wolinsky H., Sonnenblick E. H. Hypertensive-diabetic cardiomyopathy in the rat: an experimental model of human disease. Am J Pathol. 1981 Feb;102(2):219–228. [PMC free article] [PubMed] [Google Scholar]
  8. Factor S. M., Minase T., Bhan R., Wolinsky H., Sonnenblick E. H. Hypertensive diabetic cardiomyopathy in the rat: ultrastructural features. Virchows Arch A Pathol Anat Histopathol. 1983;398(3):305–317. doi: 10.1007/BF00583587. [DOI] [PubMed] [Google Scholar]
  9. Factor S. M., Minase T., Cho S., Fein F., Capasso J. M., Sonnenblick E. H. Coronary microvascular abnormalities in the hypertensive-diabetic rat. A primary cause of cardiomyopathy? Am J Pathol. 1984 Jul;116(1):9–20. [PMC free article] [PubMed] [Google Scholar]
  10. Factor S. M., Minase T., Sonnenblick E. H. Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. Am Heart J. 1980 Apr;99(4):446–458. doi: 10.1016/0002-8703(80)90379-8. [DOI] [PubMed] [Google Scholar]
  11. Fein F. S., Aronson R. S., Nordin C., Miller-Green B., Sonnenblick E. H. Altered myocardial response to ouabain in diabetic rats: mechanics and electrophysiology. J Mol Cell Cardiol. 1983 Nov;15(11):769–784. doi: 10.1016/0022-2828(83)90336-x. [DOI] [PubMed] [Google Scholar]
  12. Fein F. S., Capasso J. M., Aronson R. S., Cho S., Nordin C., Miller-Green B., Sonnenblick E. H., Factor S. M. Combined renovascular hypertension and diabetes in rats: a new preparation of congestive cardiomyopathy. Circulation. 1984 Aug;70(2):318–330. doi: 10.1161/01.cir.70.2.318. [DOI] [PubMed] [Google Scholar]
  13. Fein F. S., Kornstein L. B., Strobeck J. E., Capasso J. M., Sonnenblick E. H. Altered myocardial mechanics in diabetic rats. Circ Res. 1980 Dec;47(6):922–933. doi: 10.1161/01.res.47.6.922. [DOI] [PubMed] [Google Scholar]
  14. Fein F. S., Strobeck J. E., Malhotra A., Scheuer J., Sonnenblick E. H. Reversibility of diabetic cardiomyopathy with insulin in rats. Circ Res. 1981 Dec;49(6):1251–1261. doi: 10.1161/01.res.49.6.1251. [DOI] [PubMed] [Google Scholar]
  15. Fischer V. W., Leskiw M. L., Barner H. B. Myocardial structure and capillary basal laminar thickness in experimentally diabetic rats. Exp Mol Pathol. 1981 Oct;35(2):244–256. doi: 10.1016/0014-4800(81)90064-2. [DOI] [PubMed] [Google Scholar]
  16. Fleckenstein A., Janke J., Döring H. J., Leder O. Myocardial fiber necrosis due to intracellular Ca overload-a new principle in cardiac pathophysiology. Recent Adv Stud Cardiac Struct Metab. 1974;4:563–580. [PubMed] [Google Scholar]
  17. Ganguly P. K., Pierce G. N., Dhalla K. S., Dhalla N. S. Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol. 1983 Jun;244(6):E528–E535. doi: 10.1152/ajpendo.1983.244.6.E528. [DOI] [PubMed] [Google Scholar]
  18. Garber D. W., Everett A. W., Neely J. R. Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3, and T4. Am J Physiol. 1983 Apr;244(4):H592–H598. doi: 10.1152/ajpheart.1983.244.4.H592. [DOI] [PubMed] [Google Scholar]
  19. Garber D. W., Neely J. R. Decreased myocardial function and myosin ATPase in hearts from diabetic rats. Am J Physiol. 1983 Apr;244(4):H586–H591. doi: 10.1152/ajpheart.1983.244.4.H586. [DOI] [PubMed] [Google Scholar]
  20. Gavras H., Kremer D., Brown J. J., Gray B., Lever A. F., MacAdam R. F., medina A., Morton J. J., Robertson J. I. Angiotensin- and norepinephrine-induced myocardial lesions: experimental and clinical studies in rabbits and man. Am Heart J. 1975 Mar;89(3):321–332. doi: 10.1016/0002-8703(75)90082-4. [DOI] [PubMed] [Google Scholar]
  21. Giacomelli F., Anversa P., Wiener J. Effect of angiotensin-induced hypertension on rat coronary arteries and myocardium. Am J Pathol. 1976 Jul;84(1):111–138. [PMC free article] [PubMed] [Google Scholar]
  22. Guazzi M. D., De Cesare N., Fiorentini C., Galli C., Montorsi P., Pepi M., Tamborini G. Pulmonary vascular supersensitivity to catecholamines in systemic high blood pressure. J Am Coll Cardiol. 1986 Nov;8(5):1137–1144. doi: 10.1016/s0735-1097(86)80393-x. [DOI] [PubMed] [Google Scholar]
  23. Heyliger C. E., Pierce G. N., Singal P. K., Beamish R. E., Dhalla N. S. Cardiac alpha- and beta-adrenergic receptor alterations in diabetic cardiomyopathy. Basic Res Cardiol. 1982 Nov-Dec;77(6):610–618. doi: 10.1007/BF01908314. [DOI] [PubMed] [Google Scholar]
  24. Jackson C. V., McGrath G. M., Tahiliani A. G., Vadlamudi R. V., McNeill J. H. A functional and ultrastructural analysis of experimental diabetic rat myocardium. Manifestation of a cardiomyopathy. Diabetes. 1985 Sep;34(9):876–883. doi: 10.2337/diab.34.9.876. [DOI] [PubMed] [Google Scholar]
  25. Kannel W. B., Hjortland M., Castelli W. P. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29–34. doi: 10.1016/0002-9149(74)90089-7. [DOI] [PubMed] [Google Scholar]
  26. Kelly D. T., Spotnitz H. M., Beiser G. D., Pierce J. E., Epstein S. E. Effects of chronic right ventricular volume and pressure loading on left ventricular performance. Circulation. 1971 Sep;44(3):403–412. doi: 10.1161/01.cir.44.3.403. [DOI] [PubMed] [Google Scholar]
  27. Lopaschuk G. D., Katz S., McNeill J. H. The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines. Can J Physiol Pharmacol. 1983 May;61(5):439–448. doi: 10.1139/y83-068. [DOI] [PubMed] [Google Scholar]
  28. Lopaschuk G. D., Tahiliani A. G., Vadlamudi R. V., Katz S., McNeill J. H. Cardiac sarcoplasmic reticulum function in insulin- or carnitine-treated diabetic rats. Am J Physiol. 1983 Dec;245(6):H969–H976. doi: 10.1152/ajpheart.1983.245.6.H969. [DOI] [PubMed] [Google Scholar]
  29. Lund D. D., Twietmeyer T. A., Schmid P. G., Tomanek R. J. Independent changes in cardiac muscle fibres and connective tissue in rats with spontaneous hypertension, aortic constriction and hypoxia. Cardiovasc Res. 1979 Jan;13(1):39–44. doi: 10.1093/cvr/13.1.39. [DOI] [PubMed] [Google Scholar]
  30. Malhotra A., Penpargkul S., Fein F. S., Sonnenblick E. H., Scheuer J. The effect of streptozotocin-induced diabetes in rats on cardiac contractile proteins. Circ Res. 1981 Dec;49(6):1243–1250. doi: 10.1161/01.res.49.6.1243. [DOI] [PubMed] [Google Scholar]
  31. Mirsky I., Laks M. M. Time course of changes in the mechanical properties of the canine right and left ventricles during hypertrophy caused by pressure overload. Circ Res. 1980 Apr;46(4):530–542. doi: 10.1161/01.res.46.4.530. [DOI] [PubMed] [Google Scholar]
  32. Olivari M. T., Fiorentini C., Polese A., Guazzi M. D. Pulmonary hemodynamics and right ventricular function in hypertension. Circulation. 1978 Jun;57(6):1185–1190. doi: 10.1161/01.cir.57.6.1185. [DOI] [PubMed] [Google Scholar]
  33. Penpargkul S., Fein F., Sonnenblick E. H., Scheuer J. Depressed cardiac sarcoplasmic reticular function from diabetic rats. J Mol Cell Cardiol. 1981 Mar;13(3):303–309. doi: 10.1016/0022-2828(81)90318-7. [DOI] [PubMed] [Google Scholar]
  34. Penpargkul S., Schaible T., Yipintsoi T., Scheuer J. The effect of diabetes on performance and metabolism of rat hearts. Circ Res. 1980 Dec;47(6):911–921. doi: 10.1161/01.res.47.6.911. [DOI] [PubMed] [Google Scholar]
  35. Pierce G. N., Dhalla N. S. Cardiac myofibrillar ATPase activity in diabetic rats. J Mol Cell Cardiol. 1981 Dec;13(12):1063–1069. doi: 10.1016/0022-2828(81)90296-0. [DOI] [PubMed] [Google Scholar]
  36. Pool P. E., Piggott W. J., Seagren S. C., Skelton C. L. Augmented right ventricular function in systemic hypertension-induced hypertrophy. Cardiovasc Res. 1976 Jan;10(1):124–128. doi: 10.1093/cvr/10.1.124. [DOI] [PubMed] [Google Scholar]
  37. RONA G., CHAPPEL C. I., BALAZS T., GAUDRY R. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959 Apr;67(4):443–455. [PubMed] [Google Scholar]
  38. Shapiro L. M., Howat A. P., Calter M. M. Left ventricular function in diabetes mellitus. I: Methodology, and prevalence and spectrum of abnormalities. Br Heart J. 1981 Feb;45(2):122–128. doi: 10.1136/hrt.45.2.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Spann J. F., Jr, Buccino R. A., Sonnenblick E. H., Braunwald E. Contractile state of cardiac muscle obtained from cats with experimentally produced ventricular hypertrophy and heart failure. Circ Res. 1967 Sep;21(3):341–354. doi: 10.1161/01.res.21.3.341. [DOI] [PubMed] [Google Scholar]
  40. Vadlamudi R. V., Rodgers R. L., McNeill J. H. The effect of chronic alloxan- and streptozotocin-induced diabetes on isolated rat heart performance. Can J Physiol Pharmacol. 1982 Jul;60(7):902–911. doi: 10.1139/y82-127. [DOI] [PubMed] [Google Scholar]

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