Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jun;81(6):1850–1857. doi: 10.1172/JCI113530

Effect of age on myocardial adaptation to volume overload in the rat.

S Isoyama 1, W Grossman 1, J Y Wei 1
PMCID: PMC442635  PMID: 2968366

Abstract

To test the hypothesis that the capacity for left ventricular (LV) adaptation to volume overload might diminish with age, we examined the hemodynamics and degree of myocardial hypertrophy in response to aortic insufficiency in young adult (9 mo) and old (18 or 22 mo) Fischer rats. Before, immediately after, and at 2 and 4 wk after creating aortic insufficiency, LV and aortic pressures were measured using a catheterization technique. 4 wk after surgery, we measured aortic flow, and estimated the LV passive pressure-volume relationship and the degree of LV hypertrophy after killing. Immediately after the surgical creation of aortic insufficiency, both young and old rats showed similar elevation of LV end-diastolic pressure (from 4.8 +/- 0.6 to 12.0 +/- 1.5 mmHg in the young rats, P less than 0.01; from 4.9 +/- 0.4 to 11.0 +/- 0.7 mmHg in the old rats, P less than 0.01). In the young rats LV, end-diastolic pressure decreased to 8.0 +/- 1.0 and to 8.5 +/- 0.9 mmHg at 2 and 4 wk (P less than 0.05). In contrast, LV end-diastolic pressure at 2 (16.9 +/- 3.1 mmHg) and 4 wk (16.1 +/- 2.7 mmHg) in the old rats was even higher, compared with the values measured immediately after aortic insufficiency. At 4 wk, LV end-diastolic meridional wall stress (calculated from the in vivo LV end-diastolic pressure, and the pressure-volume relationship and muscle mass obtained after killing) was higher in the old rats than in the young rats. In the young rats, the diastolic pressure-volume relationship at 4 wk shifted to the right (P less than 0.01), and LV dry weight, LV dry weight/tibial length, and protein content of the LV myocardium increased by 26% (P less than 0.01), 24% (P less than 0.01), and 33% (P less than 0.01), respectively. However, old rats with aortic insufficiency did not show a significant change in the pressure-volume relationship, dry weight, or protein content at 4 wk. These results suggest that advanced age diminishes the capacity for LV hypertrophy in response to a volume overload, and this reduced LV hypertrophic response in the old rats resulted in persistent elevation of LV end-diastolic pressure and wall stress.

Full text

PDF
1854

Selected References

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

  1. Anversa P., Beghi C., Levicky V., McDonald S. L., Kikkawa Y. Morphometry of right ventricular hypertrophy induced by strenuous exercise in rat. Am J Physiol. 1982 Dec;243(6):H856–H861. doi: 10.1152/ajpheart.1982.243.6.H856. [DOI] [PubMed] [Google Scholar]
  2. Anversa P., Hiler B., Ricci R., Guideri G., Olivetti G. Myocyte cell loss and myocyte hypertrophy in the aging rat heart. J Am Coll Cardiol. 1986 Dec;8(6):1441–1448. doi: 10.1016/s0735-1097(86)80321-7. [DOI] [PubMed] [Google Scholar]
  3. Badke F. R., Covell J. W. Early changes in left ventricular regional dimensions and function during chronic volume overloading in the conscious dog. Circ Res. 1979 Sep;45(3):420–428. doi: 10.1161/01.res.45.3.420. [DOI] [PubMed] [Google Scholar]
  4. Flaim S. F., Minteer W. J., Nellis S. H., Clark D. P. Chronic arteriovenous shunt: evaluation of a model for heart failure in rat. Am J Physiol. 1979 May;236(5):H698–H704. doi: 10.1152/ajpheart.1979.236.5.H698. [DOI] [PubMed] [Google Scholar]
  5. Fletcher P. J., Pfeffer J. M., Pfeffer M. A., Braunwald E. Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction. Effects on systolic function. Circ Res. 1981 Sep;49(3):618–626. doi: 10.1161/01.res.49.3.618. [DOI] [PubMed] [Google Scholar]
  6. Florini J. R., Saito Y., Manowitz E. J. Effect of age on thyroxine-induced cardiac hypertrophy in mice. J Gerontol. 1973 Jul;28(3):293–297. doi: 10.1093/geronj/28.3.293. [DOI] [PubMed] [Google Scholar]
  7. GRIMM A. F., KUBOTA R., WHITEHORN W. V. Properties of myocardium in cardiomegaly. Circ Res. 1963 Jan;12:118–124. doi: 10.1161/01.res.12.1.118. [DOI] [PubMed] [Google Scholar]
  8. Geha A. S., Duffy J. P., Swan H. J. Relation of increase in muscle mass to performance of hypertrophied right ventricle in the dog. Circ Res. 1966 Aug;19(2):255–259. doi: 10.1161/01.res.19.2.255. [DOI] [PubMed] [Google Scholar]
  9. Grossman W. Cardiac hypertrophy: useful adaptation or pathologic process? Am J Med. 1980 Oct;69(4):576–584. doi: 10.1016/0002-9343(80)90471-4. [DOI] [PubMed] [Google Scholar]
  10. Grossman W., Jones D., McLaurin L. P. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975 Jul;56(1):56–64. doi: 10.1172/JCI108079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Isoyama S., Wei J. Y., Izumo S., Fort P., Schoen F. J., Grossman W. Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat. Circ Res. 1987 Sep;61(3):337–345. doi: 10.1161/01.res.61.3.337. [DOI] [PubMed] [Google Scholar]
  12. Johnson L. K., Johnson R. W., Strehler B. L. Cardiac hypertrophy, aging and changes in cardiac ribosomal RNA gene dosage in man. J Mol Cell Cardiol. 1975 Feb;7(2):125–133. doi: 10.1016/0022-2828(75)90014-0. [DOI] [PubMed] [Google Scholar]
  13. Jouannot P., Gourdier B., Hatt P. Y. L'hypertrophie cardiaque expérimentale du rat. Etude comparative de divers types de surcharge mécanique. Arch Mal Coeur Vaiss. 1973 Aug;66(8):1067–1076. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lakatta E. G. Alterations in the cardiovascular system that occur in advanced age. Fed Proc. 1979 Feb;38(2):163–167. [PubMed] [Google Scholar]
  16. Lakatta E. G., Yin F. C. Myocardial aging: functional alterations and related cellular mechanisms. Am J Physiol. 1982 Jun;242(6):H927–H941. doi: 10.1152/ajpheart.1982.242.6.H927. [DOI] [PubMed] [Google Scholar]
  17. Lee J. D., Sasayama S., Kihara Y., Ohyagi A., Fujisawa A., Yui Y., Kawai C. Adaptations of the left ventricle to chronic volume overload induced by mitral regurgitation in conscious dogs. Heart Vessels. 1985 Feb;1(1):9–15. doi: 10.1007/BF02066481. [DOI] [PubMed] [Google Scholar]
  18. Lin H. L., Katele K. V., Grimm A. F. Functional morphology of the pressure- and the volume-hypertrophied rat heart. Circ Res. 1977 Dec;41(6):830–836. doi: 10.1161/01.res.41.6.830. [DOI] [PubMed] [Google Scholar]
  19. Lipana J. G., Fanburg B. L. Heart growth in response to aortic constriction in the hypophysectomized rat. Am J Physiol. 1970 Mar;218(3):641–646. doi: 10.1152/ajplegacy.1970.218.3.641. [DOI] [PubMed] [Google Scholar]
  20. Maruyama Y., Ashikawa K., Isoyama S., Kanatsuka H., Ino-Oka E., Takishima T. Mechanical interactions between four heart chambers with and without the pericardium in canine hearts. Circ Res. 1982 Jan;50(1):86–100. doi: 10.1161/01.res.50.1.86. [DOI] [PubMed] [Google Scholar]
  21. McCafferty W. B., Edington D. W. Skeletal muscle and organ weights of aged and trained male rats. Gerontologia. 1974;20(1):44–50. doi: 10.1159/000211997. [DOI] [PubMed] [Google Scholar]
  22. McCullagh W. H., Covell J. W., Ross J., Jr Left ventricular dilatation and diastolic compliance changes during chronic volume overloading. Circulation. 1972 May;45(5):943–951. doi: 10.1161/01.cir.45.5.943. [DOI] [PubMed] [Google Scholar]
  23. Meerson F. Z., Javich M. P., Lerman M. I. Decrease in the rate of RNA and protein synthesis and degradation in the myocardium under long-term compensatory hyperfunction and on aging. J Mol Cell Cardiol. 1978 Feb;10(2):145–159. doi: 10.1016/0022-2828(78)90039-1. [DOI] [PubMed] [Google Scholar]
  24. Oparil S. Pathogenesis of ventricular hypertrophy. J Am Coll Cardiol. 1985 Jun;5(6 Suppl):57B–65B. doi: 10.1016/s0735-1097(85)80528-3. [DOI] [PubMed] [Google Scholar]
  25. Pannier J. L. Contractile state of papillary muscles obtained from cats with moderate right ventricular hypertrophy. Arch Int Physiol Biochim. 1971 Oct;79(4):743–752. doi: 10.3109/13813457109084951. [DOI] [PubMed] [Google Scholar]
  26. Pfeffer M. A., Pfeffer J. M., Fishbein M. C., Fletcher P. J., Spadaro J., Kloner R. A., Braunwald E. Myocardial infarct size and ventricular function in rats. Circ Res. 1979 Apr;44(4):503–512. doi: 10.1161/01.res.44.4.503. [DOI] [PubMed] [Google Scholar]
  27. Ross J., Jr, McCullagh W. H. Nature of enhanced performance of the dilated left ventricle in the dog during chronic volume overloading. Circ Res. 1972 May;30(5):549–556. doi: 10.1161/01.res.30.5.549. [DOI] [PubMed] [Google Scholar]
  28. Schoen F. J., Lawrie G. M., Titus J. L. Left ventricular cellular hypertrophy in pressure- and volume-overload valvular heart disease. Hum Pathol. 1984 Sep;15(9):860–865. doi: 10.1016/s0046-8177(84)80147-1. [DOI] [PubMed] [Google Scholar]
  29. Wei J. Y., Gersh B. J. Heart disease in the elderly. Curr Probl Cardiol. 1987 Jan;12(1):1–65. [PubMed] [Google Scholar]
  30. Wei J. Y., Mendelowitz D., Anastasi N., Rowe J. W. Maintenance of carotid baroreflex function in advanced age in the rat. Am J Physiol. 1986 Jun;250(6 Pt 2):R1047–R1051. doi: 10.1152/ajpregu.1986.250.6.R1047. [DOI] [PubMed] [Google Scholar]
  31. Wei J. Y., Spurgeon H. A., Lakatta E. G. Excitation-contraction in rat myocardium: alterations with adult aging. Am J Physiol. 1984 Jun;246(6 Pt 2):H784–H791. doi: 10.1152/ajpheart.1984.246.6.H784. [DOI] [PubMed] [Google Scholar]
  32. Yin F. C., Spurgeon H. A., Rakusan K., Weisfeldt M. L., Lakatta E. G. Use of tibial length to quantify cardiac hypertrophy: application in the aging rat. Am J Physiol. 1982 Dec;243(6):H941–H947. doi: 10.1152/ajpheart.1982.243.6.H941. [DOI] [PubMed] [Google Scholar]
  33. Yin F. C., Spurgeon H. A., Weisfeldt M. L., Lakatta E. G. Mechanical properties of myocardium from hypertrophied rat hearts. A comparison between hypertrophy induced by senescence and by aortic banding. Circ Res. 1980 Feb;46(2):292–300. doi: 10.1161/01.res.46.2.292. [DOI] [PubMed] [Google Scholar]
  34. Zitnik G., Roth G. S. Effects of thyroid hormones on cardiac hypertrophy and beta-adrenergic receptors during aging. Mech Ageing Dev. 1981 Jan;15(1):19–28. doi: 10.1016/0047-6374(81)90004-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES