Absence of direct actions of norepinephrine on cardiac myosin and cardiac actomyosin

Am, Katz

doi:10.1152/ajplegacy.1967.212.1.39

Cited by 16 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The constancy of PVA/(excess Vo 2) would therefore imply that the mechanical efficiency of the cross bridge cycling is also constant at 40 % on the average regardless of the loading and inotropic conditions. This seems to be compatible with the finding that myosin ATPase activity, which is known to be inversely related with the mechanical efficiency of cross bridges, is not influenced by acute isotropic interventions (KATZ, 1967;GIBBS, 1978;GIBBS and CHAPMAN, 1979). However, in contrast to acute inotropic interventions, myosin ATPase activity and the thermal economy of myocardium are known to be altered by chronic inotropic interventions in rabbits (ALPERT and MULIERI, 1982).…”

Section: Discussionsupporting

confidence: 88%

Constant mechanical efficiency of contractile machinery of canine left ventricle under different loading and inotropic conditions.

et al. 1984

View full text Add to dashboard Cite

We have recently proposed that the total mechanical energy generated in each cardiac contraction can be quantified by the systolic pressure-volume area (PVA). PVA is the area in the pressure-volume (P-V) diagram that is circumscribed by the end-systolic and end-diastolic P-V relation curves and the systolic segment of the P-V trajectory. This area has dimensions of energy and comprises the external mechanical work and the elastic potential energy. In the left ventricle of crosscirculated canine hearts, we studied the relation between PVA and oxygen consumption per beat (Vo2) above Vo2 for mechanically unloaded contraction. We assumed that this excess Vo2 is utilized for mechanical contraction by the contractile machinery. The percentage of PVA in the excess V02, both in the same unit of energy, J, would then represent the efficiency of energy conversion from the excess Vo2 to the total mechanical energy in the contractile machinery. We obtained this efficiency in variously loaded contractions in both control and enhanced contractile states with epinephrine and calcium. We found that the efficiency was constant at 30-50 (mean 40) % regardless of the changes in both loading conditions and contractile states. By this constant efficiency and a variable fraction of external work in PVA, we accounted for the load-and contractility-dependent variability of the conventional mechanical efficiency (0-30%) of the heart. Key Words; cardiac mechanics, cardiac energetics, pressure-volume area, external mechanical work, potential energy.The efficiency of conversion of energy in a system is the ratio of the useful energy deliverted by the system to the energy supplied to it. In the heart, the conventional mechanical efficiency is the ratio of the external mechanical work to the total energy supplied to the heart (EVANS and MATSUOKA, 1915;SARNOFF

show abstract

Section: Discussionsupporting

confidence: 88%

Constant mechanical efficiency of contractile machinery of canine left ventricle under different loading and inotropic conditions.

et al. 1984

View full text Add to dashboard Cite

show abstract

“…The results of most of these studies have been negative, but occasional positive results have been reported (see reference 62 for a review of some of this literature). We have found no effects of either cardiac glycosides (62) or norepinephrine (63) upon the highly purified, calcium-sensitive, reconstituted actomyosin. While these negative findings do not exclude such a direct action of these drugs, they are in accord with physiological evidence suggesting that these agents act indirectly upon the contractile proteins.…”

Section: Cardiac Actomyosinmentioning

confidence: 67%

Regulation of Cardiac Muscle Contractility

Katz

1967

The Journal of General Physiology

View full text Add to dashboard Cite

The heart's physiological performance, unlike that of skeletal muscle, is regulated primarily by variations in the contractile force developed by the individual myocardial fibers. In an attempt to identify the basis for the characteristic properties of myocardial contraction, the individual cardiac contractile proteins and their behavior in contractile models in vitro have been examined. The low shortening velocity of heart muscle appears to reflect the weak ATPase activity of cardiac myosin, but this enzymatic activity probably does not determine active state intensity. Quantification of the effects of Ca ++ upon cardiac actomyosin supports the view that myocardial contractility can be modified by changes in the amount of calcium released during excitationcontraction coupling. Exchange of intracellular K + with Na + derived from the extracellular space also could enhance myocardial contractility directly, as highly purified cardiac actomyosin is stimulated when K + is replaced by an equimolar amount of Na +. On the other hand, cardiac glycosides and catecholamines, agents which greatly increase the contractility of the intact heart, were found to be without significant actions upon highly purified reconstituted cardiac actomyosin.Regulation of contraction in mammalian cardiac and skeletal muscle, which have many common biochemical and morphological features, is achieved by different physiological mechanisms. Rapid trains of stimuli delivered to a skeletal muscle fiber through its motor nerve enhance tension development by causing the summation of individual contractile responses or, in its fully developed form, a powerful tetanic contraction. In the heart, on the other hand, fusion of contractile responses does not occur because the refractory period persists almost to the end of the active state. Recruitment of increasing numbers of active motor units plays a major role in augmenting the tension developed by a skeletal muscle, whereas all fibers of the heart, which is a functional syncytium, are normally activated during each cardiac systole.The tension generated by both cardiac and skeletal muscle fibers is influenced by initial fiber length (the length-tension relationship of skeletal muscle, and Starling's law of the heart), but the relatively less compliant myocardial fiber appears to operate with shorter sarcomeres than does that x85

show abstract

“…The mechanical energy-conversion system in myocardium is considered to be the myosin crossbridges with their ATPase activity (Huxley, 1974). Although contractile state is enhanced by epinephrine and calcium, the myosin ATPase activity is known to be uninfluenced by them in their normal ranges (Katz, 1967;Braunwald et al, 1976). In addition, the energy conversion efficiency of muscle is known to be inversely related to the myosin ATPase activity (Alpert et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Effect of positive inotropic agents on the relation between oxygen consumption and systolic pressure volume area in canine left ventricle.

Suga¹,

Hisano²,

Goto³

et al. 1983

Circulation Research

294

186

View full text Add to dashboard Cite

SUMMARY. We analyzed the effect of positive inotropic agents on the relation between left ventricular oxygen consumption and the systolic pressure-volume area. Pressure-volume area is a measure of total mechanical energy for ventricular contraction, and is a specific area in the ventricular pressure-volume diagram circumscribed by the end-systolic and end-diastolic pressurevolume relation curves and the systolic segment of the pressure-volume trajectory. Either epinephrine (1 Mg/kg per min, iv) or calcium ion (0.03 mEq/kg per min, iv) was administered to canine excised cross-circulated hearts. These agents increased an index of ventricular contractility, Emax, or the slope of the end-systolic pressure-volume line, by 70%. The regression lines of ventricular oxygen consumption on pressure-volume area in control and in enhanced contractile states were of the same formula: ventricular oxygen consumption (ml 02/beat per 100 g) equals A times pressure-volume area (mm Hg ml/beat per 100 g) plus a constant B. Coefficient A remained unchanged at 1.8 X 10~5 ml oxygen/(mm Hg ml), but constant B increased from 0.03 ml oxygen/beat per 100 g by more than 50% with either agent. The reciprocal of A reflects the energy conversion efficiency for the total mechanical energy, and this efficiency remained near 36%. The increase in B was equal to the directly measured increment in ventricular oxygen consumption for mechanically unloaded contraction. The basal metabolism remained unchanged. We conclude that the augmented oxygen consumption under the acutely enhanced contractile state with either epinephrine or calcium was caused primarily by an increased energy utilization associated with the excitation-contraction coupling. (Circ Res 53: 306-318, 1983) ENHANCEMENT of cardiac contractile state with an acutely administered positive inotropic agent is generally associated with an increase in cardiac energy utilization and oxygen consumption (Braunwald, 1969;Gibbs and Chapman, 1979). The increment in energy utilization for a given measure of mechanical contraction has been called oxygenwasting effect of the positive inotropic agent (Chandler et al., 1968;Rooke and Feigl, 1982). Although quantitative relations between the augmented energetics and the enhanced contraction have been analyzed (Sonnenblick et al., 1965;Gibbs, 1978), the mechanism of the oxygen-wasting effect has not been fully elucidated, and has been ascribed either to the enhancement of contractile state in terms of the increase in the shortening velocity (V^) of myocardium (Sonnenblick et al., 1965, Braunwald, 1969 or to the increased generation of force-independent heat associated with augmented calcium release and retrieval in the enhanced contractile state (Gibbs and Gibson, 1972;Gibbs, 1978). In addition, the effect of the positive inotropic agent on energy conversion efficiency for mechanical contraction has not been analyzed explicitly in relation to the oxygen-wasting effect. One major reason for this situation seems to be that the mechanical parameters (force, ...

show abstract

Absence of direct actions of norepinephrine on cardiac myosin and cardiac actomyosin

Cited by 16 publications

References 0 publications

Constant mechanical efficiency of contractile machinery of canine left ventricle under different loading and inotropic conditions.

Constant mechanical efficiency of contractile machinery of canine left ventricle under different loading and inotropic conditions.

Regulation of Cardiac Muscle Contractility

Effect of positive inotropic agents on the relation between oxygen consumption and systolic pressure volume area in canine left ventricle.

Contact Info

Product

Resources

About