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

Abstract

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.

Adrenergic regulation of myosin adenosine triphosphatase activity.

“…Saturation, typical of enzymatic reactions, was observed with an apparent K m of approximately 6 X 10~4 M, a value close to those measured by more traditional methods (Fig. 4) (Katz, 1970;Carey et al, 1979). The influence of the amount of enzyme on the rate of production of inorganic phosphate was determined by varying the thickness of the tissue sections, since it is not possible to vary the concentration of myosin in the tissue section.…”

Reversibility of the structural effects of pressure overload hypertrophy of cat right ventricular myocardium

“…The major components of this dysfunction are decreased systolic contractility and increased diastolic stiffness (Cooper et al, 1973a. If, in contrast, the cat right ventricle is subjected to volume overload, the in vitro function of the hypertrophied myocardium is normal (Cooper et al, 1973b;Carey et al, 1979). The sole morphological alter-ation found in pressure overloaded, but not in volume overloaded, myocardium was a disproportionate increase in connective tissue; all other structural alterations were common to both types of hypertrophy (Marino et al, 1985a,b).…”

Patterns of cellular injury in myocardial ischemia determined by monoclonal antimyosin.

“…Cardiac myosin Ca2+-activated ATPase and speed of shortening vary with isomyosin composition (16)(17)(18). The distribution of different isoenzymes of myosin among individual cardiac myocytes in several species, including the normal adult rat, is heterogeneous (19,20).…”