Structural and functional properties of myosin associated with the compensatory cardiac hypertrophy in the rabbit,

246

SUMMARY. Initial, recovery, and resting heat were measured in normal and hypertrophied papillary muscles in order to monitor the energetic consequences of the subcellular changes accompanying hypertrophy. The pulmonary artery was constricted in rabbits 4 weeks prior to measurements. Right ventricular papillary muscles were stimulated at 0.2 Hz and 21 °C in Krebs-Ringer solution under isometric conditions at optimum length. Peak twitch tension was 5.90 ± 0.25 g/mm 2 (SEM) in normal muscle (N) and 5.11 ± 0.47 g/mm 2 (NS) in pressure overload muscle (P). The maximal rate of tension generation decreased 26% (P < 0.02) from 15.9 ± 0.85 g/mm 2 sec (N) to 11.7 ± 1.37 g/mm 2 sec (P). Time-to-peak tension increased 30% (P < 0.001) from 627 ± 20 msec (N) to 816 ± 21 msec (P). The total activity related heat production per beat decreased 36% (P < 0.001) from 3.92 ± 0.26 mcal/g (N) to 2.51 ± 0.29 mcal/g (P). Initial heat was reduced 37% (P < 0.001) from 1.66 ± 0.10 mcal/g (N) to 1.04 ± 0.12 mcal/g (P). The isometric heat coefficient increased 43% (P < 0.005) from 8.76 ± 0.54 (N) to 12.5 ± 1 (P) showing increased economy in hypertrophy. There was an early fast phase (1.29 ± 0.12 mcal/g per sec) of initial heat lasting 396 ± 25 msec which was related to tension build-up. A slow phase (1.05 ± 0.07 mcal/g per sec) accompanied relaxation. In hypertrophy, the fast phase was 32% (P < 0.05) slower than normal and lasted 27% (P < 0.02) longer; the slow phase was 48% (P < 0.001) slower than normal. The ratio of recovery to initial heat (1.37 ± 0.09) was not different in N and P muscles. Resting heat was 2.08 ± 0.35 mcal/g per beat in N and 1.35 ± 0.23 mcal/g per beat in P muscles. Our present results and previous enzymatic and mechanical studies suggest that the relation between the compensated pressure overload hypertrophied and normal hearts is similar to the relation between slow and fast skeletal muscle. The changes in the heart that undergoes hypertrophy secondary to pressure overload are beneficial, since they meet the new hemodynamic demands with increased economy of force production. (Circ Res 50: 491-500, 1982)THIS investigation was undertaken to provide in vivo monitoring of subcellular changes induced by pressure overload hypertrophy in rabbit heart. The deposited film thermopile that we recently developed (Mulieri et al., 1977) is ideally suited to this study, since its low thermal capacitance, high time resolution, and sensitivity allow temperature changes accompanying an individual twitch to be correlated with the simultaneously recorded myogram. This offers the possibility of monitoring the time course of initial and recovery heat in an individual twitch response and correlating these with the intracellular mechanical and enzymatic processes known to accompany different portions of the twitch myogram.In addition, it is also of interest to compare myothermically derived values of total isometric energy liberation with values derived from oxygen consumption determinations, since the latter measurements are not in agreeme...

Section: Pressure Overload Hypertrophied Papillary Muscle Vs Normal mentioning

confidence: 50%

Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary artery constriction in the rabbit. A characterization of heat liberation in normal and hypertrophied right ventricular papillary muscles.

Alpert¹,

Mulieri²

1982

246

“…Cardiac myosin from hypertrophied myocardium due to systolic overload of the right ventricle has depressed Ca 2+ -ATPase activity. However, the percent activation of the ATPase when the Si groups are bound is greater than in myosin from control animals, but the peak activities reached are the same as controls (Shiverick et al, 1976). These studies with sulfhydrylbinding agents using cardiac myosin from hyperthyroid hearts, myosin from hearts of physically trained animals, and myosin from hypertrophied hearts all support the concept that the altered ATPase activities in these conditions may be related to a different conformation of sulfhydryl residues that changes the reactivity at or near the active site of the myosin.…”

Section: Sulfhydryl Modulationmentioning

confidence: 95%

“…An extra light chain also was reported by Henry and Sobel (1973) in myosin from hypertrophied hearts. However, most observers have not found any alterations in the ratios of light chains to heavy chains in cardiac hypertrophy Katagiri and Morkin, 1974;Shiverick et al, 1976) or other conditions that change cardiac contractile performance . Reports of extra light chains must be viewed with caution, since myosin may undergo proteolytic degradation during its purification (Siemankowski andDreizen, 1978, Bhan et al, 1978).…”

Section: Myosin Structure and Function: The Role Of Light Chainsmentioning

confidence: 99%

Cardiac contractile proteins. Adenosine triphosphatase activity and physiological function.

Scheuer¹,

Bhan²

1979

152

This review has pointed out the good correlation frequently observed between ATPase activity of various contractile protein preparations and contractile function of various muscles including the myocardium. Some of the variables in the measurement of the various ATPases and the relationship of these measurements to physiological ATPase in the intact myofibril have been mentioned. The possible roles of changes in the light chains of sulfhydryl groups in the control of ATPase activity have been outlined. The possibility that phosphorylating reactions might exert control over physiological activity remains to be clarified. It is evident that, despite the large amount of research that has been done, our understanding of how the biochemistry of contractile proteins relates to physiological function is in its infancy, and only with a more complete elucidation of the underlying biochemistry of the components of contractile proteins of physiological and pathophysiological adaptations become evident.

“…It also has been shown that depressed myosin ATPase activity accompanies the contractile deficit characteristic of severe afterload hypertrophy (Aras and Haas, 1962;Shiverick et al, 1976;Swynghedauw et al, 1973;Wikman-Coffelt et al, 1975b). Recently we demonstrated that myosin ATPase activity returns to normal in parallel with contractile function upon relief of the hemodynamic stress and reversal of hypertrophy (Carey et al, 1978a(Carey et al, , 1978b.…”

mentioning

confidence: 90%

“…This resulted in 63% right ventricular hypertrophy, normal CHRONIC pressure overload on the myocardium leads to cardiac hypertrophy and severly impaired mechanical function (Spann et al, 1967;Spann et aL, 1972;Carey et al, 1978aCarey et al, , 1978b. It also has been shown that depressed myosin ATPase activity accompanies the contractile deficit characteristic of severe afterload hypertrophy (Aras and Haas, 1962;Shiverick et al, 1976;Swynghedauw et al, 1973;Wikman-Coffelt et al, 1975b). Recently we demonstrated that myosin ATPase activity returns to normal in parallel with contractile function upon relief of the hemodynamic stress and reversal of hypertrophy (Carey et al, 1978a(Carey et al, , 1978b.…”

mentioning

confidence: 99%

Myosin adenosine triphosphatase activity in the volume-overloaded hypertrophied feline right ventricle.

Carey¹,

Natarajan²,

Bové³

et al. 1979

SUMMARY Chronic pressure overload leads to hypertrophy, depressed mechanical function, and reduced myosin ATPase activity. However, it is not known whether the lowered myosin ATPase activity results from the hypertrophic process per se or whether the elevated afterload is required for the depressed myosin ATPase activity. Further, a causal relationship between lowered myosin ATPase and weakened mechanical function in pressure overload has not been established. Chronic volume overload on the myocardium, leading to hypertrophy equivalent to that in pressure overload, allows the effects of pressure overload to be separated from the effects of hypertrophy and provides insight into the association between myosin ATPase and mechanical function. We produced large atrial septal defects (ASD) with a transvenous biopsy catheter in six adult cats. This resulted in 63% right ventricular hypertrophy, normal CHRONIC pressure overload on the myocardium leads to cardiac hypertrophy and severly impaired mechanical function (Spann et al., 1967;Spann et aL, 1972;Carey et al., 1978aCarey et al., , 1978b. It also has been shown that depressed myosin ATPase activity accompanies the contractile deficit characteristic of severe afterload hypertrophy (Aras and Haas, 1962;Shiverick et al., 1976;Swynghedauw et al., 1973;Wikman-Coffelt et al., 1975b). Recently we demonstrated that myosin ATPase activity returns to normal in parallel with contractile function upon relief of the hemodynamic stress and reversal of hypertrophy (Carey et al., 1978a(Carey et al., , 1978b. Since mechanical function and myosin ATPase activities decline and recover together, one could hypothesize that decreased myosin ATPase activity and the decreased contractile function in hypertrophy and congestive heart failure are causally related. Conversely, normal contractile function is associated with volume overload-induced hypertrophy of a magnitude equal to that observed in pressure overload (Cooper et al., 1973). Thus pressure overload rather than cardiac hypertrophy per se is required for weakened mechanical function. However, it is not known whether elevated afterload is required for a decline in myosin ATPase activity or whether hypertrophy alone is sufficient to cause a defect in myosin ATPase. Investigation of volume overload (VO) hypertrophy equal in magnitude to that observed in pressure overload allows the biochemical phenomenon associated with hypertrophy to be separated from the combined effects of hypertrophy and mechanical impairment. The purpose of this study, therefore, was to examine myosin ATPase activity in VO hypertrophy. If hypertrophy per se did not result in lowered myosin ATPase activity (and since hypertrophy alone does not cause reduced mechanical function), then additional support would be given to the hypothesis that the decline in myosin ATPase and mechanical function are causally related in pressure overload and heart failure.