Summary
Scanning electron microscopy was used to compare the shape, size, and connection of left ventricular (LV) myocytes between spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) at 3, 8, 15, 35, and 63 weeks of age. For either strain at each age, five rats were studied, in which LV myocytes consisted of a cylindrical trunk with series (SB) and/ or lateral branch(es) (LB) and step formations; cell junctions had 12 common basic patterns. The length (L), width (W), and L/W ratio of the myocytes, and various indices for SB, LB, and three selected types of cell junctions were measured in 100 cells from each heart and averaged for comparison studies. In the growing period (3–8 weeks of age), the LV myocytes were similar in shape and width in the two age-matched strains and grew similarly with the same L/W ratio. In adolescent (15-week-old) WKY, LV cells grew with the same L/W ratio as in the younger rats, whereas in adolescent SHR, the cells showed a much greater increase in width than in length (disproportionate hypertrophy), the LB proliferated significantly, and the numbers of step-to-step and side-to-side junctions were diminished. In adult (15–35-week-old) WKY, LV cells continued to grow without much change in SB, LB, and the cell junctions, whereas in adult SHR, LV hypertrophy progressed with enhanced cardiomyocyte hypertrophy, increased number of SB, LB, and step-to-end junctions, and reduction in the number of step-to-step and side-to-side junctions per cell. In aged (63-week-old) WKY and SHR, the indices of LV myocytes, SB, LB, and cell junctions did not differ from those in adult WKY and SHR, except for LB thinning in the WKY and significant LB loss in the SHR. Age-related reductions in side-to-side- and step-to-step junctions, and LB loss with myocardial fibrosis in adult and aged SHR may indicate increased loss of gap junctions which couple the cells for transverse conduction, and contribute to anisotropic discontinuous propagation and potential reentrant LV arrhythmias.
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References
Imamura K (1978) Ultrastructural aspect of left ventricular hypertrophy in spontaneously hypertensive rats: a qualitative and quantitative study. Jpn Circ J 42:979–1002
Kawamura K, Imamura K, Uehara H, Nakayama Y, Sawada K, Yamamoto S (1984) Architecture of hypertrophied myocardium: scanning and transmission electron microscopy. In: Abe H, Ito Y, Tada M, Opie LH (eds) Regulation of cardiac function. Japan Scientific, Tokyo, pp 81–105
Tomanek RJ, Hovanec JM (1981) The effects of longterm pressure overload and aging on the myocardium. J Mol Cell Cardiol 13:471–488
Nishimura H, Kubo S, Nishioka A, Imamura K, Kawamura K, Hasegawa M (1985) Left ventricular diastolic function of spontaneously hypertensive rats and its relationship to structural components of the left ventricle. Clin Sci 69:571–580.
Mirsky I, Pfeffer JM, Pfeffer MA, Braunwald E (1983) The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat. Circ Res 53:767–778
Pahor M, Giudice PL, Bernabei R, Gennaro MD, Pacifici L, Ramacci MT, Carbonin PU (1989) Age-related increase in the incidence of ventricular arrhythmias in isolated hearts from spontaneously hypertensive rats. Cardiovasc Drugs Ther 3:163–169
Kimpara T, Okabe M, Nishimura H, Hayashi T, Imamura K, Kawamura K (1997) Ultrastructural changes during myocardial hypertrophy and its regression: long-term effects of nifedipine in adult spontaneously hypertensive rats. Heart Vessels 12:143–151
Engelmann GL, Vitullo JC, Gerrity RG (1987) Morphometric analysis of cardiac hypertrophy during development, and maturation, and senescence in spontaneously hypertensive rats. Circ Res 60:487–494
Sawada K, Kawamura K (1991) Architecture of myocardial cells in human cardiac ventricles with concentric and eccentric hypertrophy as demonstrated by quantitative scanning electron microscopy. Heart Vessels 6:129–142
Yamamoto S, James TN, Sawada K, Okabe M, Kawamura K (1996) Generation of new intercellular junctions between cardiocytes. A possible mechanism compensating for mechanical overload in the hypertrophied adult myocardium. Circ Res 78:362–370
Okabe M, Kimpara T, Terasaki F, Hayashi T, Sawada K, Nishimura H, Nakayama Y, Kawamura K (1988) Scanning electron microscopic study of ventricular cardiocytes of spontaneously hypertensive rats (SHR). J Clin Electron Microsc 21:568–569
Miller BG, Woods RI, Bohlen HG (1982) A new morphologocal procedure for viewing microvessels: a scanning electron microscopic study of the vasculature of small intestine. Anat Rec 203:493–503
Inoue T, Osatake H (1988) A new drying method of biological specimens for scanning electron microscopy: The t-butyl alcohol freeze-drying method. Arch Histol Cytol 51:53–59
Bishop SP, Dillon D, Naftilan J, Reynolds R (1980) Surface morphology of isolated cardiac myocytes from hypertrophied hearts of aging spontaneously hypertensive rats. In: SEM/1980/II, Inc. AMF O'Hare, Chicago, IL 60666, USA, pp 193–199
Severs NJ, Shovel KS, Slade AM, Powell T, Twist VW, Green CR (1989) Fate of gap junctions in isolated adult mammalian cardiomyocytes. Circ Res 65:22–42
Severs NJ, Slade AM, Powell T, Twist VW, Warren RL (1982) Correlation of ultrastructure and function in calcium tolerant myocytes isolated from the adult rat heart. J Ultrastruct Res 81:222–239
Mazet F, Wittenberg BA, Spray DC (1985) Fate of intercellular junctions in isolated adult rat cardiac cells. Circ Res 56:195–204
Spach MS, Dolber PC (1986) Relating extracellular potentials and their derivatives to anisotropic propagation at microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res 58:356–371
Spach MS (1997) Discontinuous cardiac conduction: its origin in cellular connectivity with long-term adaptive changes that cause arrhythmias. In: Spooner PM, Joyner RW, Jolife J (eds) Discontinuous conduction in the heart. Futura, Armonk, pp 5–51
Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Capasso JM (1990) Hypertensive cardiomyopathy. Myocyte nuclei hyperplasia in the mammalian rat heart. J Clin Invest 85:994–997
Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Meggs LG, Capasso JM (1990) Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res 67:871–885
Anversa P, Fitzpatrick D, Argani S, Capasso JM (1991) Myocyte mitotic division in the aging mammalian rat heart. Circ Res 69:1159–1164
Olivetti G, Melissari M, Balbi T, Quaini F, Sonnenblick EH, Anversa P (1994) Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans. J Am Coll Cardiol 24:140–149
Hamet P, Richard L, Dam TV, Teiger E, Orlov SN, Gaboury L, Gossard F, Tremblay J (1995) Apoptosis in target organs of hypertension. Hypertension 26:642–648
Díez J, Fortuño MA, Ravassa S (1998) Apoptosis in hypertensive heart disease. Curr Opin Cardiol 13:317–325
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This study was supported in part by a Grant-in-Aid for Scientific Research (02454262) from the Japanese Ministry of Education, Science and Culture, and by the Vehicle Racing Commemorative Foundation.
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Okabe, M., Kawamura, K., Terasaki, F. et al. Remodeling of cardiomyocytes and their branches in juvenile, adult, and senescent spontaneously hypertensive rats and Wistar Kyoto rats: Comparative morphometric analyses by scanning electron microscopy. Heart Vessels 14, 15–28 (1999). https://doi.org/10.1007/BF02481739
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DOI: https://doi.org/10.1007/BF02481739