Cellular basis of contractile derangements of hypertrophied feline ventricular myocytes

被引:59
作者
Bailey, BA [1 ]
Dipla, K [1 ]
Li, SY [1 ]
Houser, SR [1 ]
机构
[1] TEMPLE UNIV, SCH MED, DEPT PHYSIOL, PHILADELPHIA, PA 19140 USA
关键词
myofibrillar Ca2+ sensitivity; Ca-2+ transients; internal load; heart failure; pressure overload;
D O I
10.1006/jmcc.1997.0422
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The objective of this study was to further explore the cellular basis of the reduced rate and magnitude of contraction of feline left ventricular myocytes with severe hypertrophy induced by slow progressive pressure overload. A 3.0 mm internal diameter band was placed around the ascending aorta of 12 young (8-10 weeks old) cats, and sham operations were performed in 13 others. This caused no major pressure overload initially, but 15 weeks later there was a significant pressure gradient across the band (56 +/- 14 mmHg) and the heart weight to body weight ratio had increased from 4.2-7 gm/kg. Contraction rates and magnitudes of myocytes isolated from the hearts with hypertrophy (LVH) were significantly slower and smaller, respectively, than those from control (C) animals. Indo-1 fluorescence transients in LVH myocytes were significantly smaller in magnitude and longer in duration than in C, suggesting that: contractile defects result from Ca2+ derangements. Elevation of bath Ca2+ increased the peak Indo-1 fluorescence and the rate and magnitude of contraction in all myocytes. At the bath Ca2+ which had maximal inotropic effects there were no differences in the peals. Indo-1 fluorescence in LVH and C myocytes, but contraction magnitude remained significantly smaller in LVH, This suggests that there are Ca2+-independent contractile derangements in LVH, In support of this hypothesis, the relationship between contraction magnitude and the peak Indo-1 fluorescence (index of myofibrillar Ca2+ sensitivity) was significantly shifted in LVH myocytes, suggesting that myofibrillar Ca2+ sensitivity was reduced. There was also a significant shift of the terminal portions of hysteresis loops of cell length nu indo-1 fluorescence ratio, providing additional support for this idea. Experiments with isoproterenol suggest that it can reduce myofibrillar Ca2+ sensitivity in C, but not LVH myocytes. The idea that increased internal resistance to shortening (internal load) is responsible for the contractile defects of LVH myocytes was examined by defining the relationship between the rate of relengthening and the magnitude of shortening. There was no significant difference in this relation between C and LVH myocytes. In addition, colchicine (which depolymerizes microtubular tubulin) had no significant effect on contraction magnitude in either C or LVH myocytes. These results suggest that the contractile properties of feline LVH myocytes result from changes in cellular Ca2+ regulation and myofibrillar Ca2+ sensitivity but not from changes in the internal loading. (C) 1997 Academic Press Limited.
引用
收藏
页码:1823 / 1835
页数:13
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