Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH). This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height2.7 as a proxy for lean body mass and body mass index (BMI) as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally. 1. Introduction Early reports concerning myocyte size in the human left ventricle, relying heavily upon autopsy specimens [1–3], often found that [4] “the individual contractile muscle cells … are roughly cylindrical … measuring 17 to 25？μm in diameter and 60 to 140？μm in length,” giving length to diameter ratio of about 5 to 1. Recent studies, relying on enzymatic isolation of myocytes into suspension from surgical specimens [5–14], commonly model myocytes as elliptic cylinders of variable eccentricities and length to width ratios under assorted conditions [5–7]. Variations between these models, arising from disparate methodologies, call for further inquiry to resolve their causes. Cross-sectional profiles of myocytes, whether isolated or in sections, display a daunting irregularity of outline, especially of major axis, although less so of the minor axis. Measurements of minor axis are therefore emphasized in this report of findings with H&E-stained paraffin sections of forensic autopsy specimens. Left ventricular mass increases in many hyperergopathic states, often culminating in systolic dysfunction [15, 16]. Behavior by the full range of myocyte sizes, and not just their average, merits attention. Several authors [7–10] have reported unimodal distribution curves of myocyte sizes, consistently showing conspicuous upward skewness. These authors did not report statistical curve fitting; however, graphic inspection raised the possibility of log normal fits, which could imply that the smallest and the largest myocytes may all respond alike [7–9], a possibility seldom discussed. Grant et al. [17] stated a rarely encountered
References
[1]
L. M. Ashley, “A determination of the diameters of ventricular myocardial fibers in man and other mammals,” American Journal of Anatomy, vol. 77, no. 11, pp. 325–359, 1945.
[2]
A. J. Linzbach, “Heart failure from the point of view of quantitative anatomy,” The American Journal of Cardiology, vol. 5, no. 3, pp. 370–382, 1960.
[3]
R. Zak, “Development and proliferative capacity of cardiac muscle cells,” Circulation Research, vol. 35, supplement 2, pp. 17–26, 1974.
[4]
L. H. Opi, “Mechanisms of cardiac contraction and relaxation,” in Heart Disease: A Textbook of Cardiovascular Medicine, E. Braunwald, D. P. Zipes, and P. Libby, Eds., vol. 1, p. 443, W. B. Saunders, Philadelphia, Pa, USA, 2001.
[5]
A. M. Gerdes, J. M. Capasso, J. Schaper et al., “Structural remodeling and mechanical dysfunction of cardiac myocytes in heart failure,” Journal of Molecular and Cellular Cardiology, vol. 27, no. 3, pp. 849–865, 1995.
[6]
A. M. Gerdes, S. E. Kellerman, K. B. Malec, and D. D. Schocken, “Transverse shape characteristics of cardiac myocytes from rats and humans,” Cardioscience, vol. 5, no. 1, pp. 31–36, 1994.
[7]
A. Zafeiridis, V. Jeevanandam, S. R. Houser, and K. B. Margulies, “Regression of cellular hypertrophy after left ventricular assist device support,” Circulation, vol. 98, no. 7, pp. 656–662, 1998.
[8]
B. Korecky and K. Rakusan, “Normal and hypertrophic growth of the rat heart: changes in cell dimensions and number,” The American journal of physiology, vol. 234, no. 2, pp. H123–128, 1978.
[9]
S. E. Campbell, B. Korecky, and K. Rakusan, “Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts,” Circulation Research, vol. 68, no. 4, pp. 984–996, 1991.
[10]
S. Said, T. Tamura, and A. Martin Gerdes, “Measurement of isolated myocyte volume using the Coulter models Z2 and ZM/C256: a comparison of instrument function,” BioTechniques, vol. 25, no. 3, pp. 522–525, 1998.
[11]
A. M. Gerdes, J. A. Moore, and J. M. Hines, “Regional differences in myocyte size in normal rat heart,” Anatomical Record, vol. 215, no. 4, pp. 420–426, 1986.
[12]
A. M. Gerdes, “Cardiac myocyte remodeling in hypertrophy and progression to failure,” Journal of Cardiac Failure, vol. 8, no. 6, pp. S264–S268, 2002.
[13]
T. Tamura, T. Onodera, S. Said, and A. M. Gerdes, “Correlation of myocyte lengthening to chamber dilation in the spontaneously hypertensive heart failure (SHHF) rat,” Journal of Molecular and Cellular Cardiology, vol. 30, no. 11, pp. 2175–2181, 1998.
[14]
A. M. Gerdes, T. Onodera, T. Tamura et al., “New method to evaluate myocyte remodeling from formalin-fixed biopsy and autopsy material,” Journal of Cardiac Failure, vol. 4, no. 4, pp. 343–348, 1998.
[15]
S. R. Houser and K. B. Margulies, “Is depressed myocyte contractility centrally involved in heart failure?” Circulation Research, vol. 92, no. 4, pp. 350–358, 2003.
[16]
A. M. Katz, “Cardiomyopathy of overload: a major determinant of prognosis in congestive heart failure,” The New England Journal of Medicine, vol. 322, no. 2, pp. 100–110, 1990.
[17]
C. Grant, D. G. Greene, and I. L. Bunnell, “Left ventricular enlargement and hypertrophy. A clinical and angiocardiographic study,” The American Journal of Medicine, vol. 39, no. 6, pp. 895–904, 1965.
[18]
B. J. Maron and W. C. Roberts, “Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy,” Circulation, vol. 59, no. 4, pp. 689–706, 1979.
[19]
K. E. Bove, D. T. Rowlands, and R. C. Scott, “Observations on the assessment of cardiac hypertrophy utilizing a chamber partition technique,” Circulation, vol. 33, no. 4, pp. 558–568, 1966.
[20]
R. B. Devereux, K. Wachtell, E. Gerdts et al., “Prognostic significance of left ventricular mass change during treatment of hypertension,” Journal of the American Medical Association, vol. 292, no. 19, pp. 2350–2356, 2004.
[21]
G. F. Bahr, G. Bloom, and U. Friberg, “Volume changes of tissues in physiological fluids during fixation in osmium tetroxide or formaldehyde and during subsequent treatment,” Experimental Cell Research, vol. 12, no. 2, pp. 342–355, 1957.
[22]
R. J. Siegel, K. Swan, G. Edwalds, and M. C. Fishbein, “Limitations of postmortem assessment of human coronary artery size and luminal narrowing: differential effects of tissue fixation and processing on vessels with different degrees of atherosclerosis,” Journal of the American College of Cardiology, vol. 5, no. 2 I, pp. 342–346, 1985.
[23]
L. E. Teichholz, T. Kreulen, M. V. Herman, and R. Gorlin, “Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence or absence of asynergy,” The American Journal of Cardiology, vol. 37, no. 1, pp. 7–11, 1976.
[24]
R. E. Tracy, D. N. Lanjewar, K. G. Ghorpade, A. G. Valand, and S. R. Raghuwanshi, “Renovasculopathies in elderly normotensives of Bombay, India,” Geriatric nephrology and urology, vol. 7, no. 2, pp. 101–109, 1997.
[25]
R. E. Tracy, “The heterogeneity of vascular findings in the kidneys of patients with benign essential hypertension,” Nephrology Dialysis Transplantation, vol. 14, no. 7, pp. 1634–1639, 1999.
[26]
G. De Simone, S. R. Daniels, R. B. Devereux et al., “Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight,” Journal of the American College of Cardiology, vol. 20, no. 5, pp. 1251–1260, 1992.
[27]
P. Anversa, R. Ricci, and G. Olivetti, “Guantitative structural analysis of the myocardium during physiological growth and induced cardiac hypertrophy: a review,” Journal of the American College of Cardiology, vol. 7, no. 5, pp. 1140–1149, 1986.
[28]
W. Grossman, D. Jones, and L. P. McLaurin, “Wall stress and patterns of hypertrophy in the human left ventricle,” Journal of Clinical Investigation, vol. 56, no. 1, pp. 56–64, 1975.
