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. 1991 Jun;87(6):2077–2086. doi: 10.1172/JCI115238

Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

K Nakano 1, M M Swindle 1, F Spinale 1, K Ishihara 1, S Kanazawa 1, A Smith 1, R W Biederman 1, L Clamp 1, Y Hamada 1, M R Zile 1, et al.
PMCID: PMC296964  PMID: 1828252

Abstract

It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload.

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Selected References

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  1. 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]
  2. Belcher P., Boerboom L. E., Olinger G. N. Standardization of end-systolic pressure-volume relation in the dog. Am J Physiol. 1985 Sep;249(3 Pt 2):H547–H553. doi: 10.1152/ajpheart.1985.249.3.H547. [DOI] [PubMed] [Google Scholar]
  3. Belenkie I., Baumber J. S., Rademaker A. Changes in left ventricular dimensions and performance resulting from acute and chronic volume overload in the conscious dog. Can J Physiol Pharmacol. 1983 Nov;61(11):1274–1280. doi: 10.1139/y83-184. [DOI] [PubMed] [Google Scholar]
  4. Berko B., Gaasch W. H., Tanigawa N., Smith D., Craige E. Disparity between ejection and end-systolic indexes of left ventricular contractility in mitral regurgitation. Circulation. 1987 Jun;75(6):1310–1319. doi: 10.1161/01.cir.75.6.1310. [DOI] [PubMed] [Google Scholar]
  5. Bonow R. O., Dodd J. T., Maron B. J., O'Gara P. T., White G. G., McIntosh C. L., Clark R. E., Epstein S. E. Long-term serial changes in left ventricular function and reversal of ventricular dilatation after valve replacement for chronic aortic regurgitation. Circulation. 1988 Nov;78(5 Pt 1):1108–1120. doi: 10.1161/01.cir.78.5.1108. [DOI] [PubMed] [Google Scholar]
  6. Bonow R. O., Rosing D. R., Maron B. J., McIntosh C. L., Jones M., Bacharach S. L., Green M. V., Clark R. E., Epstein S. E. Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of duration of preoperative left ventricular dysfunction. Circulation. 1984 Oct;70(4):570–579. doi: 10.1161/01.cir.70.4.570. [DOI] [PubMed] [Google Scholar]
  7. Borow K. M., Green L. H., Grossman W., Braunwald E. Left ventricular end-systolic stress-shortening and stress-length relations in human. Normal values and sensitivity to inotropic state. Am J Cardiol. 1982 Dec;50(6):1301–1308. doi: 10.1016/0002-9149(82)90467-2. [DOI] [PubMed] [Google Scholar]
  8. Brickner M. E., Starling M. R. Dissociation of end systole from end ejection in patients with long-term mitral regurgitation. Circulation. 1990 Apr;81(4):1277–1286. doi: 10.1161/01.cir.81.4.1277. [DOI] [PubMed] [Google Scholar]
  9. Burkhoff D., Sugiura S., Yue D. T., Sagawa K. Contractility-dependent curvilinearity of end-systolic pressure-volume relations. Am J Physiol. 1987 Jun;252(6 Pt 2):H1218–H1227. doi: 10.1152/ajpheart.1987.252.6.H1218. [DOI] [PubMed] [Google Scholar]
  10. Canty J. M., Jr Coronary pressure-function and steady-state pressure-flow relations during autoregulation in the unanesthetized dog. Circ Res. 1988 Oct;63(4):821–836. doi: 10.1161/01.res.63.4.821. [DOI] [PubMed] [Google Scholar]
  11. Carabello B. A., Green L. H., Grossman W., Cohn L. H., Koster J. K., Collins J. J., Jr Hemodynamic determinants of prognosis of aortic valve replacement in critical aortic stenosis and advanced congestive heart failure. Circulation. 1980 Jul;62(1):42–48. doi: 10.1161/01.cir.62.1.42. [DOI] [PubMed] [Google Scholar]
  12. Carabello B. A., Nakano K., Corin W., Biederman R., Spann J. F., Jr Left ventricular function in experimental volume overload hypertrophy. Am J Physiol. 1989 Apr;256(4 Pt 2):H974–H981. doi: 10.1152/ajpheart.1989.256.4.H974. [DOI] [PubMed] [Google Scholar]
  13. Carabello B. A., Nolan S. P., McGuire L. B. Assessment of preoperative left ventricular function in patients with mitral regurgitation: value of the end-systolic wall stress-end-systolic volume ratio. Circulation. 1981 Dec;64(6):1212–1217. doi: 10.1161/01.cir.64.6.1212. [DOI] [PubMed] [Google Scholar]
  14. Carabello B. A., Spann J. F. The uses and limitations of end-systolic indexes of left ventricular function. Circulation. 1984 May;69(5):1058–1064. doi: 10.1161/01.cir.69.5.1058. [DOI] [PubMed] [Google Scholar]
  15. Carabello B. A., Williams H., Gash A. K., Kent R., Belber D., Maurer A., Siegel J., Blasius K., Spann J. F. Hemodynamic predictors of outcome in patients undergoing valve replacement. Circulation. 1986 Dec;74(6):1309–1316. doi: 10.1161/01.cir.74.6.1309. [DOI] [PubMed] [Google Scholar]
  16. Colan S. D., Borow K. M., Neumann A. Left ventricular end-systolic wall stress-velocity of fiber shortening relation: a load-independent index of myocardial contractility. J Am Coll Cardiol. 1984 Oct;4(4):715–724. doi: 10.1016/s0735-1097(84)80397-6. [DOI] [PubMed] [Google Scholar]
  17. Corin W. J., Swindle M. M., Spann J. F., Jr, Nakano K., Frankis M., Biederman R. W., Smith A., Taylor A., Carabello B. A. Mechanism of decreased forward stroke volume in children and swine with ventricular septal defect and failure to thrive. J Clin Invest. 1988 Aug;82(2):544–551. doi: 10.1172/JCI113630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Eckberg D. L., Gault J. H., Bouchard R. L., Karliner J. S., Ross J., Jr Mechanics of left ventricular contraction in chronic severe mitral regurgitation. Circulation. 1973 Jun;47(6):1252–1259. doi: 10.1161/01.cir.47.6.1252. [DOI] [PubMed] [Google Scholar]
  19. Florenzano F., Glantz S. A. Left ventricular mechanical adaptation to chronic aortic regurgitation in intact dogs. Am J Physiol. 1987 May;252(5 Pt 2):H969–H984. doi: 10.1152/ajpheart.1987.252.5.H969. [DOI] [PubMed] [Google Scholar]
  20. Freeman G. L., Little W. C., O'Rourke R. A. The effect of vasoactive agents on the left ventricular end-systolic pressure-volume relation in closed-chest dogs. Circulation. 1986 Nov;74(5):1107–1113. doi: 10.1161/01.cir.74.5.1107. [DOI] [PubMed] [Google Scholar]
  21. Gash A. K., Carabello B. A., Cepin D., Spann J. F. Left ventricular ejection performance and systolic muscle function in patients with mitral stenosis. Circulation. 1983 Jan;67(1):148–154. doi: 10.1161/01.cir.67.1.148. [DOI] [PubMed] [Google Scholar]
  22. Gibson J. G., Seligman A. M., Peacock W. C., Aub J. C., Fine J., Evans R. D. THE DISTRIBUTION OF RED CELLS AND PLASMA IN LARGE AND MINUTE VESSELS OF THE NORMAL DOG, DETERMINED BY RADIOACTIVE ISOTOPES OF IRON AND IODINE. J Clin Invest. 1946 Nov;25(6):848–857. doi: 10.1172/JCI101772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Goldman M. E., Mora F., Guarino T., Fuster V., Mindich B. P. Mitral valvuloplasty is superior to valve replacement for preservation of left ventricular function: an intraoperative two-dimensional echocardiographic study. J Am Coll Cardiol. 1987 Sep;10(3):568–575. doi: 10.1016/s0735-1097(87)80199-7. [DOI] [PubMed] [Google Scholar]
  24. Hugenholtz P. G., Kaplan E., Hull E. Determination of left ventricular wall thickness by angiocardiography. Am Heart J. 1969 Oct;78(4):513–522. doi: 10.1016/0002-8703(69)90486-4. [DOI] [PubMed] [Google Scholar]
  25. Kass D. A., Beyar R., Lankford E., Heard M., Maughan W. L., Sagawa K. Influence of contractile state on curvilinearity of in situ end-systolic pressure-volume relations. Circulation. 1989 Jan;79(1):167–178. doi: 10.1161/01.cir.79.1.167. [DOI] [PubMed] [Google Scholar]
  26. Kleaveland J. P., Kussmaul W. G., Vinciguerra T., Diters R., Carabello B. A. Volume overload hypertrophy in a closed-chest model of mitral regurgitation. Am J Physiol. 1988 Jun;254(6 Pt 2):H1034–H1041. doi: 10.1152/ajpheart.1988.254.6.H1034. [DOI] [PubMed] [Google Scholar]
  27. Krahwinkel D. J., Jr, Sawyer D. C., Eyster G. E., Bender G. Cardiopulmonary effects of fentanyl-droperidol, nitrous oxide, and atropine sulfate in dogs. Am J Vet Res. 1975 Aug;36(08):1211–1219. [PubMed] [Google Scholar]
  28. LeWinter M. M., Engler R. L., Karliner J. S. Enhanced left ventricular shortening during chronic volume overload in conscious dogs. Am J Physiol. 1980 Feb;238(2):H126–H133. doi: 10.1152/ajpheart.1980.238.2.H126. [DOI] [PubMed] [Google Scholar]
  29. Little W. C., Cheng C. P., Peterson T., Vinten-Johansen J. Response of the left ventricular end-systolic pressure-volume relation in conscious dogs to a wide range of contractile states. Circulation. 1988 Sep;78(3):736–745. doi: 10.1161/01.cir.78.3.736. [DOI] [PubMed] [Google Scholar]
  30. Mirsky I. Assessment of passive elastic stiffness of cardiac muscle: mathematical concepts, physiologic and clinical considerations, directions of future research. Prog Cardiovasc Dis. 1976 Jan-Feb;18(4):277–308. doi: 10.1016/0033-0620(76)90023-2. [DOI] [PubMed] [Google Scholar]
  31. Mirsky I., Tajimi T., Peterson K. L. The development of the entire end-systolic pressure-volume and ejection fraction-afterload relations: a new concept of systolic myocardial stiffness. Circulation. 1987 Aug;76(2):343–356. doi: 10.1161/01.cir.76.2.343. [DOI] [PubMed] [Google Scholar]
  32. Nakano K., Sugawara M., Ishihara K., Kanazawa S., Corin W. J., Denslow S., Biederman R. W., Carabello B. A. Myocardial stiffness derived from end-systolic wall stress and logarithm of reciprocal of wall thickness. Contractility index independent of ventricular size. Circulation. 1990 Oct;82(4):1352–1361. doi: 10.1161/01.cir.82.4.1352. [DOI] [PubMed] [Google Scholar]
  33. Nakano K., Sugawara M., Kato T., Sasayama S., Carabello B. A., Asanoi H., Umemura J., Koyanagi H. Regional work of the human left ventricle calculated by wall stress and the natural logarithm of reciprocal of wall thickness. J Am Coll Cardiol. 1988 Dec;12(6):1442–1448. doi: 10.1016/s0735-1097(88)80007-x. [DOI] [PubMed] [Google Scholar]
  34. Nakano K., Sugawara M., Tamiya K., Satomi G., Koyanagi H. A new approach to defining regional work of the ventricle and evaluating regional cardiac function: mean wall stress-natural logarithm of reciprocal of wall thickness relationship. Heart Vessels. 1986;2(2):74–80. doi: 10.1007/BF02059959. [DOI] [PubMed] [Google Scholar]
  35. Pitarys C. J., 2nd, Forman M. B., Panayiotou H., Hansen D. E. Long-term effects of excision of the mitral apparatus on global and regional ventricular function in humans. J Am Coll Cardiol. 1990 Mar 1;15(3):557–563. doi: 10.1016/0735-1097(90)90625-y. [DOI] [PubMed] [Google Scholar]
  36. RACKLEY C. E., DODGE H. T., COBLE Y. D., Jr, HAY R. E. A METHOD FOR DETERMINING LEFT VENTRICULAR MASS IN MAN. Circulation. 1964 May;29:666–671. doi: 10.1161/01.cir.29.5.666. [DOI] [PubMed] [Google Scholar]
  37. Schuler G., Peterson K. L., Johnson A., Francis G., Dennish G., Utley J., Daily P. O., Ashburn W., Ross J., Jr Temporal response of left ventricular performance to mitral valve surgery. Circulation. 1979 Jun;59(6):1218–1231. doi: 10.1161/01.cir.59.6.1218. [DOI] [PubMed] [Google Scholar]
  38. Starling M. R., Walsh R. A., Dell'Italia L. J., Mancini G. B., Lasher J. C., Lancaster J. L. The relationship of various measures of end-systole to left ventricular maximum time-varying elastance in man. Circulation. 1987 Jul;76(1):32–43. doi: 10.1161/01.cir.76.1.32. [DOI] [PubMed] [Google Scholar]
  39. Suga H., Sagawa K., Shoukas A. A. Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res. 1973 Mar;32(3):314–322. doi: 10.1161/01.res.32.3.314. [DOI] [PubMed] [Google Scholar]
  40. Sugawara M., Nakano K. A method of analyzing regional myocardial function: mean wall stress-area strain relationship. Jpn Circ J. 1987 Jan;51(1):120–124. doi: 10.1253/jcj.51.120. [DOI] [PubMed] [Google Scholar]
  41. Sugawara M., Tamiya K., Nakano K. Regional work of the ventricle: wall tension--area relation. Heart Vessels. 1985 Aug;1(3):133–144. doi: 10.1007/BF02066408. [DOI] [PubMed] [Google Scholar]
  42. Taylor R. R., Covell J. W., Ross J., Jr Left ventricular function in experimental aorto-caval fistula with circulatory congestion and fluid retention. J Clin Invest. 1968 Jun;47(6):1333–1342. doi: 10.1172/JCI105825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tsuiki K., Ritman E. L. Direct evidence that left ventricular myocardium is incompressible throughout systole and diastole. Tohoku J Exp Med. 1980 Sep;132(1):119–120. doi: 10.1620/tjem.132.119. [DOI] [PubMed] [Google Scholar]
  44. Turina M., Bussmann W. D., Krayenbühl H. P. Contractility of the hypertrophied canine heart in chronic volume overload. Cardiovasc Res. 1969 Oct;3(4):486–495. doi: 10.1093/cvr/3.4.486. [DOI] [PubMed] [Google Scholar]
  45. Urschel C. W., Covell J. W., Sonnenblick E. H., Ross J., Jr, Braunwald E. Myocardial mechanics in aortic and mitral valvular regurgitation: the concept of instantaneous impedance as a determinant of the performance of the intact heart. J Clin Invest. 1968 Apr;47(4):867–883. doi: 10.1172/JCI105780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wisenbaugh T., Spann J. F., Carabello B. A. Differences in myocardial performance and load between patients with similar amounts of chronic aortic versus chronic mitral regurgitation. J Am Coll Cardiol. 1984 Apr;3(4):916–923. doi: 10.1016/s0735-1097(84)80349-6. [DOI] [PubMed] [Google Scholar]
  47. Wisenbaugh T., Yu G., Evans J. The superiority of maximum fiber elastance over maximum stress-volume ratio as an index of contractile state. Circulation. 1985 Sep;72(3):648–653. doi: 10.1161/01.cir.72.3.648. [DOI] [PubMed] [Google Scholar]
  48. Wong C. Y., Spotnitz H. M. Systolic and diastolic properties of the human left ventricle during valve replacement for chronic mitral regurgitation. Am J Cardiol. 1981 Jan;47(1):40–50. doi: 10.1016/0002-9149(81)90287-3. [DOI] [PubMed] [Google Scholar]

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