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. 1992 Jun;89(6):1825–1838. doi: 10.1172/JCI115787

Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure.

K Komamura 1, R P Shannon 1, A Pasipoularides 1, T Ihara 1, A S Lader 1, T A Patrick 1, S P Bishop 1, S F Vatner 1
PMCID: PMC295881  PMID: 1601992

Abstract

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.

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  1. Aroesty J. M., McKay R. G., Heller G. V., Royal H. D., Als A. V., Grossman W. Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia. Circulation. 1985 May;71(5):889–900. doi: 10.1161/01.cir.71.5.889. [DOI] [PubMed] [Google Scholar]
  2. Bers D. M., Bridge J. H. Relaxation of rabbit ventricular muscle by Na-Ca exchange and sarcoplasmic reticulum calcium pump. Ryanodine and voltage sensitivity. Circ Res. 1989 Aug;65(2):334–342. doi: 10.1161/01.res.65.2.334. [DOI] [PubMed] [Google Scholar]
  3. Blaustein A. S., Gaasch W. H. Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate. Am J Physiol. 1983 Mar;244(3):H417–H422. doi: 10.1152/ajpheart.1983.244.3.H417. [DOI] [PubMed] [Google Scholar]
  4. Bonow R. O., Rosing D. R., Bacharach S. L., Green M. V., Kent K. M., Lipson L. C., Maron B. J., Leon M. B., Epstein S. E. Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy. Circulation. 1981 Oct;64(4):787–796. doi: 10.1161/01.cir.64.4.787. [DOI] [PubMed] [Google Scholar]
  5. Bortone A. S., Hess O. M., Chiddo A., Gaglione A., Locuratolo N., Caruso G., Rizzon P. Functional and structural abnormalities in patients with dilated cardiomyopathy. J Am Coll Cardiol. 1989 Sep;14(3):613–623. doi: 10.1016/0735-1097(89)90102-2. [DOI] [PubMed] [Google Scholar]
  6. Cheng C. P., Freeman G. L., Santamore W. P., Constantinescu M. S., Little W. C. Effect of loading conditions, contractile state, and heart rate on early diastolic left ventricular filling in conscious dogs. Circ Res. 1990 Mar;66(3):814–823. doi: 10.1161/01.res.66.3.814. [DOI] [PubMed] [Google Scholar]
  7. Chow E., Woodard J. C., Farrar D. J. Rapid ventricular pacing in pigs: an experimental model of congestive heart failure. Am J Physiol. 1990 May;258(5 Pt 2):H1603–H1605. doi: 10.1152/ajpheart.1990.258.5.H1603. [DOI] [PubMed] [Google Scholar]
  8. Coleman H. N., 3rd, Taylor R. R., Pool P. E., Whipple G. H., Covell J. W., Ross J., Jr, Braunwald E. Congestive heart failure following chronic tachycardia. Am Heart J. 1971 Jun;81(6):790–798. doi: 10.1016/0002-8703(71)90083-4. [DOI] [PubMed] [Google Scholar]
  9. Dawson M. J., Gadian D. G., Wilkie D. R. Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. J Physiol. 1980 Feb;299:465–484. doi: 10.1113/jphysiol.1980.sp013137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dougherty A. H., Naccarelli G. V., Gray E. L., Hicks C. H., Goldstein R. A. Congestive heart failure with normal systolic function. Am J Cardiol. 1984 Oct 1;54(7):778–782. doi: 10.1016/s0002-9149(84)80207-6. [DOI] [PubMed] [Google Scholar]
  11. Eckberg D. L., Drabinsky M., Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971 Oct 14;285(16):877–883. doi: 10.1056/NEJM197110142851602. [DOI] [PubMed] [Google Scholar]
  12. Fujii A. M., Gelpi R. J., Mirsky I., Vatner S. F. Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy. Circ Res. 1988 Mar;62(3):462–470. doi: 10.1161/01.res.62.3.462. [DOI] [PubMed] [Google Scholar]
  13. Gaasch W. H., Battle W. E., Oboler A. A., Banas J. S., Jr, Levine H. J. Left ventricular stress and compliance in man. With special reference to normalized ventricular function curves. Circulation. 1972 Apr;45(4):746–762. doi: 10.1161/01.cir.45.4.746. [DOI] [PubMed] [Google Scholar]
  14. Gaasch W. H., Blaustein A. S., Andrias C. W., Donahue R. P., Avitall B. Myocardial relaxation. II. Hemodynamic determinants of rate of left ventricular isovolumic pressure decline. Am J Physiol. 1980 Jul;239(1):H1–H6. doi: 10.1152/ajpheart.1980.239.1.H1. [DOI] [PubMed] [Google Scholar]
  15. Gaasch W. H., Carroll J. D., Blaustein A. S., Bing O. H. Myocardial relaxation: effects of preload on the time course of isovolumetric relaxation. Circulation. 1986 May;73(5):1037–1041. doi: 10.1161/01.cir.73.5.1037. [DOI] [PubMed] [Google Scholar]
  16. Gaasch W. H., Cole J. S., Quinones M. A., Alexander J. K. Dynamic determinants of letf ventricular diastolic pressure-volume relations in man. Circulation. 1975 Feb;51(2):317–323. doi: 10.1161/01.cir.51.2.317. [DOI] [PubMed] [Google Scholar]
  17. Gelpi R. J., Pasipoularides A., Lader A. S., Patrick T. A., Chase N., Hittinger L., Shannon R. P., Bishop S. P., Vatner S. F. Changes in diastolic cardiac function in developing and stable perinephritic hypertension in conscious dogs. Circ Res. 1991 Feb;68(2):555–567. doi: 10.1161/01.res.68.2.555. [DOI] [PubMed] [Google Scholar]
  18. Grossman W., McLaurin L. P., Rolett E. L. Alterations in left ventricular relaxation and diastolic compliance in congestive cardiomyopathy. Cardiovasc Res. 1979 Sep;13(9):514–522. doi: 10.1093/cvr/13.9.514. [DOI] [PubMed] [Google Scholar]
  19. Grossman W., McLaurin L. P., Stefadouros M. A. Left ventricular stiffness associated with chronic pressure and volume overloads in man. Circ Res. 1974 Nov;35(5):793–800. doi: 10.1161/01.res.35.5.793. [DOI] [PubMed] [Google Scholar]
  20. Hess O. M., Grimm J., Krayenbuehl H. P. Diastolic simple elastic and viscoelastic properties of the left ventricle in man. Circulation. 1979 Jun;59(6):1178–1187. doi: 10.1161/01.cir.59.6.1178. [DOI] [PubMed] [Google Scholar]
  21. Hess O. M., Ritter M., Schneider J., Grimm J., Turina M., Krayenbuehl H. P. Diastolic stiffness and myocardial structure in aortic valve disease before and after valve replacement. Circulation. 1984 May;69(5):855–865. doi: 10.1161/01.cir.69.5.855. [DOI] [PubMed] [Google Scholar]
  22. Hess O. M., Schneider J., Koch R., Bamert C., Grimm J., Krayenbuehl H. P. Diastolic function and myocardial structure in patients with myocardial hypertrophy. Special reference to normalized viscoelastic data. Circulation. 1981 Feb;63(2):360–371. doi: 10.1161/01.cir.63.2.360. [DOI] [PubMed] [Google Scholar]
  23. Higgins C. B., Vatner S. F., Eckberg D. L., Braunwald E. Alterations in the baroreceptor reflex in conscious dogs with heart failure. J Clin Invest. 1972 Apr;51(4):715–724. doi: 10.1172/JCI106865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hittinger L., Shannon R. P., Bishop S. P., Gelpi R. J., Vatner S. F. Subendomyocardial exhaustion of blood flow reserve and increased fibrosis in conscious dogs with heart failure. Circ Res. 1989 Oct;65(4):971–980. doi: 10.1161/01.res.65.4.971. [DOI] [PubMed] [Google Scholar]
  25. Hittinger L., Shannon R. P., Kohin S., Lader A. S., Manders W. T., Patrick T. A., Kelly P., Vatner S. F. Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure. Circulation. 1989 Sep;80(3):658–668. doi: 10.1161/01.cir.80.3.658. [DOI] [PubMed] [Google Scholar]
  26. Jalil J. E., Doering C. W., Janicki J. S., Pick R., Shroff S. G., Weber K. T. Fibrillar collagen and myocardial stiffness in the intact hypertrophied rat left ventricle. Circ Res. 1989 Jun;64(6):1041–1050. doi: 10.1161/01.res.64.6.1041. [DOI] [PubMed] [Google Scholar]
  27. Karliner J. S., LeWinter M. M., Mahler F., Engler R., O'Rourke R. A. Pharmacologic and hemodynamic influences on the rate of isovolumic left ventricular relaxation in the normal conscious dog. J Clin Invest. 1977 Sep;60(3):511–521. doi: 10.1172/JCI108803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Katayama K., Matsuzaki M., Khono M., Fujii T., Ohtani N., Yatabe S., Ogawa H., Ozaki M., Matsuda Y., Kusukawa R. Global and regional diastolic filling dynamics in compensated dilated cardiomyopathy. Jpn Circ J. 1990 Jun;54(6):624–635. doi: 10.1253/jcj.54.624. [DOI] [PubMed] [Google Scholar]
  29. Katayama K., Tajimi T., Guth B. D., Matsuzaki M., Lee J. D., Seitelberger R., Peterson K. L. Early diastolic filling dynamics during experimental mitral regurgitation in the conscious dog. Circulation. 1988 Aug;78(2):390–400. doi: 10.1161/01.cir.78.2.390. [DOI] [PubMed] [Google Scholar]
  30. Martin G., Gimeno J. V., Cosin J., Guillem M. I. Time constant of isovolumic pressure fall: new numerical approaches and significance. Am J Physiol. 1984 Aug;247(2 Pt 2):H283–H294. doi: 10.1152/ajpheart.1984.247.2.H283. [DOI] [PubMed] [Google Scholar]
  31. Mirsky I. Assessment of diastolic function: suggested methods and future considerations. Circulation. 1984 Apr;69(4):836–841. doi: 10.1161/01.cir.69.4.836. [DOI] [PubMed] [Google Scholar]
  32. Mirsky I., Cohn P. F., Levine J. A., Gorlin R., Herman M. V., Kreulen T. H., Sonnenblick E. H. Assessment of left ventricular stiffness in primary myocardial disease and coronary artery disease. Circulation. 1974 Jul;50(1):128–136. doi: 10.1161/01.cir.50.1.128. [DOI] [PubMed] [Google Scholar]
  33. Mirsky I., Pfeffer J. M., Pfeffer M. A., Braunwald E. The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat. Circ Res. 1983 Dec;53(6):767–778. doi: 10.1161/01.res.53.6.767. [DOI] [PubMed] [Google Scholar]
  34. Morgan D. E., Tomlinson C. W., Qayumi A. K., Toleikis P. M., McConville B., Jamieson W. R. Evaluation of ventricular contractility indexes in the dog with left ventricular dysfunction induced by rapid atrial pacing. J Am Coll Cardiol. 1989 Aug;14(2):489–498. doi: 10.1016/0735-1097(89)90206-4. [DOI] [PubMed] [Google Scholar]
  35. Nakayama Y., Shimizu G., Hirota Y., Saito T., Kino M., Kitaura Y., Kawamura K. Functional and histopathologic correlation in patients with dilated cardiomyopathy: an integrated evaluation by multivariate analysis. J Am Coll Cardiol. 1987 Jul;10(1):186–192. doi: 10.1016/s0735-1097(87)80178-x. [DOI] [PubMed] [Google Scholar]
  36. Nayler W. G., Williams A. Relaxation in heart muscle: some morphological and biochemical considerations. Eur J Cardiol. 1978 Jun;7 (Suppl):35–50. [PubMed] [Google Scholar]
  37. Pagani M., Baig H., Sherman A., Manders W. T., Quinn P., Patrick T., Franklin D., Vatner S. F. Measurement of multiple simultaneous small dimensions and study of arterial pressure-dimension relations in conscious animals. Am J Physiol. 1978 Nov;235(5):H610–H617. doi: 10.1152/ajpheart.1978.235.5.H610. [DOI] [PubMed] [Google Scholar]
  38. Parker J. D., Landzberg J. S., Bittl J. A., Mirsky I., Colucci W. S. Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle. Circulation. 1991 Sep;84(3):1040–1048. doi: 10.1161/01.cir.84.3.1040. [DOI] [PubMed] [Google Scholar]
  39. Pasipoularides A., Mirsky I., Hess O. M., Grimm J., Krayenbuehl H. P. Myocardial relaxation and passive diastolic properties in man. Circulation. 1986 Nov;74(5):991–1001. doi: 10.1161/01.cir.74.5.991. [DOI] [PubMed] [Google Scholar]
  40. Perlini S., Soffiantino F., Farilla C., Soldá P., Calciati A., Paro M., Finardi G., Bernardi L. Load dependence of isovolumic relaxation in intact heart: facts or artifacts? Cardiovasc Res. 1988 Jan;22(1):47–54. doi: 10.1093/cvr/22.1.47. [DOI] [PubMed] [Google Scholar]
  41. Perreault C. L., Shannon R. P., Komamura K., Vatner S. F., Morgan J. P. Abnormalities in intracellular calcium regulation and contractile function in myocardium from dogs with pacing-induced heart failure. J Clin Invest. 1992 Mar;89(3):932–938. doi: 10.1172/JCI115674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rankin J. S., McHale P. A., Arentzen C. E., Ling D., Greenfield J. C., Jr, Anderson R. W. The three-dimensional dynamic geometry of the left ventricle in the conscious dog. Circ Res. 1976 Sep;39(3):304–313. doi: 10.1161/01.res.39.3.304. [DOI] [PubMed] [Google Scholar]
  43. Renlund D. G., Lakatta E. G., Mellits E. D., Gerstenblith G. Calcium-dependent enhancement of myocardial diastolic tone and energy utilization dissociates systolic work and oxygen consumption during low sodium perfusion. Circ Res. 1985 Dec;57(6):876–888. doi: 10.1161/01.res.57.6.876. [DOI] [PubMed] [Google Scholar]
  44. Shannon R. P., Komamura K., Stambler B. S., Bigaud M., Manders W. T., Vatner S. F. Alterations in myocardial contractility in conscious dogs with dilated cardiomyopathy. Am J Physiol. 1991 Jun;260(6 Pt 2):H1903–H1911. doi: 10.1152/ajpheart.1991.260.6.H1903. [DOI] [PubMed] [Google Scholar]
  45. Soufer R., Wohlgelernter D., Vita N. A., Amuchestegui M., Sostman H. D., Berger H. J., Zaret B. L. Intact systolic left ventricular function in clinical congestive heart failure. Am J Cardiol. 1985 Apr 1;55(8):1032–1036. doi: 10.1016/0002-9149(85)90741-6. [DOI] [PubMed] [Google Scholar]
  46. Spinale F. G., Hendrick D. A., Crawford F. A., Smith A. C., Hamada Y., Carabello B. A. Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine. Am J Physiol. 1990 Jul;259(1 Pt 2):H218–H229. doi: 10.1152/ajpheart.1990.259.1.H218. [DOI] [PubMed] [Google Scholar]
  47. Spinale F. G., Zellner J. L., Tomita M., Crawford F. A., Zile M. R. Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy. Circ Res. 1991 Oct;69(4):1058–1067. doi: 10.1161/01.res.69.4.1058. [DOI] [PubMed] [Google Scholar]
  48. Spinale F. G., Zellner J. L., Tomita M., Tempel G. E., Crawford F. A., Zile M. R. Tachycardia-induced cardiomyopathy: effects on blood flow and capillary structure. Am J Physiol. 1991 Jul;261(1 Pt 2):H140–H148. doi: 10.1152/ajpheart.1991.261.1.H140. [DOI] [PubMed] [Google Scholar]
  49. Starling M. R., Montgomery D. G., Mancini G. B., Walsh R. A. Load independence of the rate of isovolumic relaxation in man. Circulation. 1987 Dec;76(6):1274–1281. doi: 10.1161/01.cir.76.6.1274. [DOI] [PubMed] [Google Scholar]
  50. Tomita M., Spinale F. G., Crawford F. A., Zile M. R. Changes in left ventricular volume, mass, and function during the development and regression of supraventricular tachycardia-induced cardiomyopathy. Disparity between recovery of systolic versus diastolic function. Circulation. 1991 Feb;83(2):635–644. doi: 10.1161/01.cir.83.2.635. [DOI] [PubMed] [Google Scholar]
  51. WOESSNER J. F., Jr The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961 May;93:440–447. doi: 10.1016/0003-9861(61)90291-0. [DOI] [PubMed] [Google Scholar]
  52. Weber K. T., Janicki J. S., Shroff S. G., Pick R., Chen R. M., Bashey R. I. Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circ Res. 1988 Apr;62(4):757–765. doi: 10.1161/01.res.62.4.757. [DOI] [PubMed] [Google Scholar]
  53. Weber K. T., Pick R., Silver M. A., Moe G. W., Janicki J. S., Zucker I. H., Armstrong P. W. Fibrillar collagen and remodeling of dilated canine left ventricle. Circulation. 1990 Oct;82(4):1387–1401. doi: 10.1161/01.cir.82.4.1387. [DOI] [PubMed] [Google Scholar]
  54. Weiss J. L., Frederiksen J. W., Weisfeldt M. L. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest. 1976 Sep;58(3):751–760. doi: 10.1172/JCI108522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Wilson J. R., Douglas P., Hickey W. F., Lanoce V., Ferraro N., Muhammad A., Reichek N. Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects. Circulation. 1987 Apr;75(4):857–867. doi: 10.1161/01.cir.75.4.857. [DOI] [PubMed] [Google Scholar]
  56. Yellin E. L., Hori M., Yoran C., Sonnenblick E. H., Gabbay S., Frater R. W. Left ventricular relaxation in the filling and nonfilling intact canine heart. Am J Physiol. 1986 Apr;250(4 Pt 2):H620–H629. doi: 10.1152/ajpheart.1986.250.4.H620. [DOI] [PubMed] [Google Scholar]
  57. Zellner J. L., Spinale F. G., Eble D. M., Hewett K. W., Crawford F. A., Jr Alterations in myocyte shape and basement membrane attachment with tachycardia-induced heart failure. Circ Res. 1991 Sep;69(3):590–600. doi: 10.1161/01.res.69.3.590. [DOI] [PubMed] [Google Scholar]

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