Heart and Vessels

, Volume 1, Issue 1, pp 9–15 | Cite as

Adaptations of the left ventricle to chronic volume overload induced by mitral regurgitation in conscious dogs

  • Jong Dae Lee
  • Shigetake Sasayama
  • Yasuki Kihara
  • Akira Ohyagi
  • Akiko Fujisawa
  • Yoshiki Yui
  • Chuichi Kawai


To assess the time-course of adaptive responses of the left ventricle to chronic volume overload, dogs were instrumented with a left ventricular (LV) micromanometer and pairs of ultrasonic crystals for the measurement of LV wall thickness (WTh), LV chamber diameter (D), and longitudinal segment length (L). Following a control study, mitral regurgitation (MR) was created by a transventricular section of the chordae tendineae. Heart rate was controlled during each study by atrial pacing. Plasma norepinephrine levels at rest were determined by high-performance liquid chromatography. Eight days (mean) after the onset of MR, end-diastolic (ED) D had increased by 9% from 34.2±2.4 mm (SEM) (P<0.001), wit significant thinning of the wall thickness (from 8.2 to 7.7 mm,P<0.001). Consequently the calculated cross-sectional area (CSA) of the left ventricular wall remained the same. Peak wall stress (WSt) and EDWSt increased by 20% and 152%, respectively. During the subsequent 4 weeks, EDD progressively increased, averaging 11% above the control at 4 weeks, while EDWTh returned to the control level. Thus, the development of hypertrophy was clearly evidenced by an increase in CSA (by 8% over the control,P<0.001). These changes were accompanied by a consistent reduction in both peak WSt and EDWSt. Mean velocity of circumferential fiber shortening (meanVcf) and percentage shortening were significantly augmented following the onset of MR and remained at the same level thereafter, indicating no further use of the Frank-Starling mechanisms during chronic ventricular dilation. Despite a progressive increase in diameter, longitudinal segment length did not increase throughout the study, suggesting that the ventricle assumes a more globular appearance, as an additional compensatory mechanism to prevent excessive enhancement of diastolic wall stress, Initially elevated plasma norepinephrine concentrations (from 127±28 to 256±69 pg/ml,P<0.05) tended to decrease with the development of hypertrophy (202±55 pg/ml). These data support the view that hypertrophy and change in shape of the left ventricle take place during the course of chronic adaptation to volume overload and normalize the elevated wall stress as a negative feedback. Along with the decrease in wall stress, the initially enhanced sympathetic activity decreases gradually during adaptation to chronic volume overload.

Key words

Chronic volume overload Mitral regurgitation Left ventricular hypertrophy Sympathetic activity 


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  1. 1.
    Taylor RR, Covell JW, Ross J Jr (1968) Left ventricular function in experimental aorto-caval fistula with circulatory congestion and fluid retention. J Clin Invest 47: 1333–1342PubMedGoogle Scholar
  2. 2.
    Ross J Jr, McCullagh WH (1972) Nature of enhanced performance of the dilated left ventricle in the dog during chronic volume overloading. Circ Res 30: 549–556PubMedGoogle Scholar
  3. 3.
    Badke FR, Covell JW (1979) Early changes in left ventricular regional dimensions and function during chronic volume overloading in conscious dog. Circ Res 45: 420–428PubMedGoogle Scholar
  4. 4.
    LeWinter MM, Engler RI, Karliner JS (1980) Enhanced left ventricular shortening during chronic volume overload in conscious dogs. Am J Physiol 238: H126-H133PubMedGoogle Scholar
  5. 5.
    Ross J Jr, Sonnenblick EH, Taylor RR, Spotnitz HM, Covell JW (1971) Diastolic geometry and sarcomere lengths in the chronically dilated canine left ventricle. Circ Res 28: 49–61PubMedGoogle Scholar
  6. 6.
    Grant C, Greene DG, Bunnel IL (1965) Left ventricular enlargement and hypertrophy: A clinical and angiocardiographic study. Am J Med 39: 895–904PubMedGoogle Scholar
  7. 7.
    Falsetti HL, Mates RE, Grant C, Greene DG, Bunnell IL (1970) Left ventricular wall stress calculated from one-plane cineangiography: an approach to force-velocity analysis in man. Circ Res 26: 71–83PubMedGoogle Scholar
  8. 8.
    Grossman W, Jones D, McLaurin LP (1975) Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 56: 56–64PubMedGoogle Scholar
  9. 9.
    Sasayama S, Ross J Jr, Franklin D, Bloor CM, Bishop S, Dilley RB (1976) Adaptations of the left ventricle to chronic pressure overload. Circ Res 38: 172–178PubMedGoogle Scholar
  10. 10.
    Sasayama S, Takahashi M, Osakada G, Hirose K, Hamashima H, Nishimura E, Kawai C (1979) Dynamic geometry of the left atrium and left ventricle in acute mitral regurgitation. Circulation 60: 177–186PubMedGoogle Scholar
  11. 11.
    Yui Y, Fujita T, Yamamoto T, Itokawa Y, Kawai C (1980) Liquid-chromatographic determination of norepinephrine and epinephrine in human plasma. Clin Chem 26: 194–196PubMedGoogle Scholar
  12. 12.
    Bishop SP (1972) Structural alterations of the myocardium induced by chronic work overload. Adv Exp Med Biol 22: 289–314PubMedGoogle Scholar
  13. 13.
    Zar JH (1974) Biostatistical analysis. Prentice-Hall, Englewood Cliffs, pp 151–155Google Scholar
  14. 14.
    Vokonas PS, Gorlin R, Cohn PF, Herman MV, Sonnenblick EH (1973) Dynamic geometry of the left ventricle in mitral regurgitation. Circulation 48: 786–796PubMedGoogle Scholar
  15. 15.
    Fischl JS, Gorlin R, Herman MV (1971) Cardiac shape and function in aortic valve disease: physiologic and clinical implication. Am J Cardiol 39: 170–176Google Scholar
  16. 16.
    Newman WH (1978) Contractile state of hypertrophied left ventricle in long-standing volume overload. Am J Physiol 234: H88-H93PubMedGoogle Scholar
  17. 17.
    Crozatier B, Caillet D, Chevrier JL, Hatt PY (1982) Nonsympathetic increased inotropic state early after aortic insufficiency. Am J Physiol 242: H973-H979PubMedGoogle Scholar
  18. 18.
    Laks MM, Morady F, Swan HJC (1973) Myocardial hypertrophy produced by chronic infusion of subhypertensive doses of norepinephrine in the dog. Chest 64: 75–780PubMedGoogle Scholar
  19. 19.
    Yamaguchi N, De Champlain J, Nadeau R (1975) Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog. Circ Res 36: 662–668PubMedGoogle Scholar
  20. 20.
    Lake CR, Ziegler MG, Kopin IJ (1976) Use of plasma norepinephrine for evaluation of sympathetic neuronal function in man. Life Sci 18: 1315–1326PubMedGoogle Scholar
  21. 21.
    Kopin IJ, Lake RC, Ziegler M (1978) Plasma level of norepiniphrine. Ann Intern Med 88: 671–680PubMedGoogle Scholar
  22. 22.
    Goldstein DS (1981) Plasma norepinephrine as an indicator of sympathetic neural activity in clinical cardiology. Am J Cardiol 48: 1147–1154PubMedGoogle Scholar
  23. 23.
    Rossi MA, Carillo SV, Oliveira JSM (1981) The effect of iron deficiency anemia in the rat on catecholamine levels and heart morphology. Cardiovasc Res 15: 313–319PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Jong Dae Lee
    • 1
  • Shigetake Sasayama
    • 1
  • Yasuki Kihara
    • 1
  • Akira Ohyagi
    • 1
  • Akiko Fujisawa
    • 1
  • Yoshiki Yui
    • 1
  • Chuichi Kawai
    • 1
  1. 1.The Third Division, Department of Internal Medicine, Faculty of MedicineKyoto UniversityKyotoJapan

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