Contractile Element Work Research Articles

Systolic pressure-volume area (PVA) as the energy of contraction in Starling's law of the heart

We have theoretically proposed "systolic pressure-volume area" (PVA) as a measure of total mechanical energy generated by ventricular contraction. We then experimentally showed that PVA closely correlates with left ventricular oxygen consumption (Vo2) regardless of ventricular loading conditions in a stable contractile state. Although Starling's law of the heart has been generally considered to describe the relation between ventricular preload as the input and the "energy of contraction" as the output, the energy of cardiac contraction has been variously identified with cardiac output, external work, contractile element work, tension-time index, etc., by different investigators. However, none of these variables has been unanimously accepted as the total mechanical energy of contraction because they do not consistently correlate with Vo2 which represents the total energy utilization for contraction. Considering the nature of PVA which has been revealed over the last decade, we now confidently propose that PVA is the most likely expression of the total mechanical energy of contraction that has been pursued for many years as the energy of contraction in Starling's law of the heart.

An Energetic Model of Muscle Contraction

Initial energy utilization in the twitch is visualized as the result of the activity of two distinct processes. The first is the calcium-pumping activity of the sarcoplasmic reticulum, which has a constant energy requirement under normal conditions. The second is the chemomechanical transduction process consisting of a variable number of quantal contractile events, each with a fixed enthalpy equal to the molecular enthalpy of adenosine triphosphate (ATP) hydrolysis in vivo. This enthalpy appears either as heat or as contractile element work. Total enthalpy varies according to the number of quantal contractile events that occur in the twitch cycle. The basis of the variation is suggested to be velocity-dependent activity of the actomyosin ATPase, allowing more quantal events to occur in a contraction cycle when shortening occurs. The classical designation "activation heat" is held to be appropriate for the first process. The partition of the enthalpy of the second process that is currently in vogue is held to be misleading and a new formulation is suggested in which the properties of the quantal contractile event are reflected in general terms. The formulation of the proposed transduction model represents a conceptual return to the viscoelastic theory, but at a quantal level. The model can explain the results of the preceding paper and is adaptable to different muscles without having to postulate fundamental differences in energy utilization.

Mechanochemistry of cardiac muscle. V. Influence of thyroid state on energy utilization.

The possibility that alterations in the rate or efficiency of energy utilization could be involved in the control of cellular oxygen consumption by thyroid hormone was examined in right ventricular papillary muscles isolated from normal euthyroid cats and cats with experimentally induced hyperthyroidism and hypothyroidism. Energy production in the muscles was inhibited and isolated from the process of energy utilization by exposure to iodoacetic acid and nitrogen. After resting or performing variable amounts of contractile element work under isometric conditions, muscles were frozen, and the total amount of chemical energy ( approximately P = creatine phosphate + ATP) used was determined. The resting rate of energy utilization in muscles from euthyroid animals was 0.78+/-0.07 mumoles/g per min of approximately P. This rate was elevated in muscles from hyperthyroid cats to 1.00+/-0.09 mumoles/g per min and decreased in muscles from hypothyroid cats to 0.23+/-0.14 mumoles/g per min. Isometrically contracting muscles from cats with hypothyroidism utilized only 64% as much energy as muscles from euthyroid cats while performing 81% as much contractile element work at a moderately decreased level of contractile state. Muscles from hyperthyroid cats utilized an average of 41% more energy than did muscles from euthyroid cats while contracting an identical number of times and performing an equal amount of contractile element work at a slightly increased level of contractile state. These results suggest that thyroid hormone directly influences the rate of cellular energy utilization. Furthermore, the increase in energy utilization in muscles from hyperthyroid cats could not be attributed entirely to observed alterations in contractile behavior, which indicates that excess thyroid hormone may decrease the efficiency of the conversion of cellular energy to work. However, the opposite effect, an increased efficiency of energy utilization, was not observed in muscles from hypothyroid cats. Thus, it is concluded that the calorigenic effects of thyroid hormone may be explained, at least in part, by alterations in the process of energy utilization.

Energy production in cardiac isotonic contractions.

The energy output of rabbit papillary muscle is examined and it is shown that there is more energy liberated in an afterloaded isotonic contraction than in an "equivalent" isometric contraction. This statement holds true regardless of whether equivalence is based on the proposition that tension or the time integral of tension is the best index of muscle energy expenditure. Besides the external work performed there is additional heat production in isotonic contractions and this heat increases as the afterload is decreased. The additional heat is more evident when tension rather than the time integral of tension is made the determinant of energy expenditure. It is shown in single contractions that the rate of isotonic heat production, regardless of afterload size, never exceeds the heat rate recorded in an isometric contraction at the same initial length. Experiments reveal no simple linear correlation between isotonic energy output and contractile element work. Problems associated with the compartmentalization of the energy output of a contraction are discussed.

Mechanochemistry of Cardiac Muscle

This investigation was designed to determine whether a defect in energy utilization exists in heart failure. Accordingly, the direct conversion of chemical energy to mechanical work was studied in right ventricular papillary muscles from normal cats and cats with experimental right ventricular failure secondary to pulmonary artery constriction. Energy production was inhibited by iodoacetic acid and N 2 . After resting or performing variable amounts of internal contractile element work under isometric conditions, muscles were instantly frozen, and the total amount of chemical energy (∼ P = creatine phosphate + ATP) used was correlated with work performed and the number of contractions. The contractile properties of papillary muscles from cats with heart failure were severely depressed. There was a significant depression in initial ∼P stores in muscles from cats with heart failure, but there was no significant change in the resting rate of ∼P utilization. Although the muscles from cats with heart failure performed, on the average, 13% as much work and were activated 64% as many times, the average amount of energy used was only 7% of that used by normal muscles. It is concluded that in this form of experimentally produced heart failure the utilization of ∼P is reduced but only in relation to the reduction in contractile element work and that the direct conversion of chemical energy to mechanical work is not an inefficient process in this state.

Effects of norepinephrine and phenylephrine on myocardial energetics

The effects of intravenous norepinephrine and phenylephrine on myocardial V̇ O 2 of 20 intact anesthetized dogs were studied. Ventricular pressure, flow, volume, and V̇ O 2 were measured, and mean systolic force, pressure-time and force-time, fiber velocity, work and power of cardiac contraction were calculated. The best correlation of V̇ O 2 was with power in the control state but there was also a significant correlation of V̇ O 2 with work and force parameters. This correlation remained highly significant during catecholamine infusion only for work and power, whereas the correlation with pressure-time or force-time disappeared. Stroke work correlated closely (r = 0.96) with contractile element work. Myocardial anaerobiosis did not conribute significantly to energy requirement. The mean efficiency of contraction was slightly increased by these agents. Correlation of V̇ O 2 with stroke power or contractile element power was not significantly better than the correlation with stroke work, suggesting that the net effect, if any, of fiber velocity on myocardial oxygen consumption in the intact heart is small.

Effects of acute valvular regurgitation on the oxygen consumption of the canine heart.

The effects on myocardial oxygen consumption and mechanics of acute, simulated aortic and mitral regurgitation were studied in open-chest, anesthetized dogs to determine how changes in the mechanical performance of the ventricle alter oxygen consumption. When regurgitation was induced acutely with effective stroke volume (total stroke volume less regurgitant volume) and heart rate held constant, left ventricular end-diastolic volume, total stroke volume, the ejection fraction, left ventricular wall tension, and the extent of shortening of the contractile element and the circumferential fibers all increased. With volumes of regurgitation approaching effective systemic blood flow, oxygen consumption increased only moderately, despite the increases in tension and shortening. When valvular regurgitation was induced while peak ventricular wall tension was held relatively constant, stroke volume doubled and the extent of both contractile element and circumferential fiber shortening increased. Contractile element work in generating tension was unchanged; that which led to fiber shortening increased substantially. Myocardial oxygen consumption did not increase significantly. Thus, marked increases in the efficiency of the contractile elements and myocardial fibers occurred. The low energy cost per unit of work expended in shortening as opposed to that used for tension development therefore allows the excess stroke volume of valvular regurgitation to be maintained at only a small added oxygen cost to the ventricle.

Myocardial mechanics in aortic and mitral valvular regurgitation: the concept of instantaneous impedance as a determinant of the performance of the intact heart.

The effects on myocardial mechanics of acute, artificial aortic and mitral regurgitation were studied in the dog to determine the manner in which the changes in load induced by valvular regurgitation alter ventricular performance. With mitral and aortic regurgitant volumes of approximately the same magnitude as the forward stroke volume, immediate increases occurred in total stroke volume, left ventricular enddiastolic pressure, and peak ejection velocity, whereas contractility remained unchanged. Although calculated myocardial fiber tension rose, the rate of decline of tension during ejection was accelerated with regurgitation due to the more rapid decrease in ventricular size. Average tension therefore decreased relative to average pressure. As a consequence of the increased fiber length and this unloading, contractile element velocity, work, and power were increased. Despite unchanged contractility of the myocardium, the ejection fraction rose with both aortic and mitral regurgitation.When regurgitant beats were compared with control beats at a constant end-diastolic volume, ventricular stroke volume, work, power, and ejection fraction, as well as contractile element velocity, work, and power consistently increased. Thus, reduction of instantaneous impedance to ejection allowed the ventricle to empty further, reducing ventricular wall tension with a resultant increase in the velocity of shortening. External energy output was increased despite unchanged contractility and diastolic fiber length. It is concluded that the impedance to ejection and myocardial fiber tension during ejection govern the velocity and extent of contractile element shortening, and hence affect stroke volume, peak aortic flow rate, and ejection fraction. The alterations of ventricular function accompanying valvular regurgitation can be explained by an evaluation of the effects of these lesions on the instantaneous impedance to left ventricular ejection.

Myocardial oxygen consumption in acute experimental cardiac depression.

Myocardial oxygen consumption (MV · o 2 ) during drug-induced cardiac depression was measured in 8 anesthetized, open chest dogs in which myocardial wall tension was controlled. The right side of the heart was bypassed and myocardial contractility was reduced with procaine HCl, propranolol, or pronethalol. MV · o 2 consistently fell during cardiac depression (avg = 1.52 ml/min per 100 g left ventricle or - 11.6%). These reductions occurred despite small increases in developed tension. Changes in the tension-time index, contractile element work, and contractile element power did not correlate invariably with ΔMV · o 2 , while reductions in velocity of the contractile elements at isotension, maximum left ventricular dp/dt, and the extent of shortening of the contractile elements and circumferential fibers were associated in every experiment with the reductions in MV · o 2 . The finding that negative inotropic influences are associated with a reduction in myocardial energy utilization, when considered with earlier observations showing that positive inotropic influences induce an augmentation of MV · o 2 , provides evidence that the inotropic state and its mechanical correlates are coupled with myocardial energy utilization by a mechanism that is independent of tension development.

Myocardial Oxygen Consumption, Left Ventricular Fibre Shortening and Wall Tension

Myocardial oxygen consumption ( MVO 2) was studied in a canine right heart bypass preparation. At constant heart rate and left ventricular peak developed tension (calculated from ventricular volume and pressure), doubling cardiac inflow increased MVO 2 by 1·3 ml./100 g LV/min. This approximate 10% increase is attributed to increased contractile element shortening and work.

The Mechanochemistry of Cardiac Muscle

The utilization of creatine phosphate (CP) and adenosine triphosphate (ATP) was studied in the iodoacetate (IAA) and nitrogen (N(2))-treated cat papillary muscle. Under these conditions the net production of ATP does not occur, and the net utilization of ATP is reflected in a fall in CP concentration. The rate of energy utilization of the IAA-N(2)-treated cat papillary muscle resting without tension was 0.68 micromole CP/g/min. This rate was increased to 1.07 micromole/g/min when muscles were passively stretched with 2 g of tension. In a series of isometrically contracting muscles CP utilization was found to be proportional to the number of activations and the summated contractile element work. These rates of CP utilization were 0.083 micromole/g/activation and 0.0059 micromole/g-cm of work. The calculated mechanochemical coupling efficiency was 33%.

The mechanics of left ventricular contraction in acute experimental cardiac failure.

The effects of acute cardiac failure induced by pentobarbital or pronethalol on the basic mechanical properties of the intact left ventricle were examined in the dog, and the influence on auxotonic and isovolumic contractions of the increase in end-diastolic volume that usually accompanies cardiac failure was assessed. The right heart bypass preparation was employed, and isovolumic beats were induced by sudden balloon occlusion of the aortic root. The ventricular pressure-volume curve was determined directly, and the mechanical responses of the myocardial fibers and contractile elements were calculated.When end-diastolic pressure was held constant, failure reduced the extent of circumferential fiber shortening, and the tension-velocity relation calculated during isovolumic beats was always shifted, with reductions in both maximal velocity (average decrease 30%) and maximal developed tension (average 23%); in addition, during failure achievement of maximal contractile element velocity and maximal tension was delayed, whereas the total duration of contraction was always prolonged. Acetylstrophanthidin tended to reverse all of these changes. When end-diastolic volume was augmented during failure at a constant stroke volume, the extent of circumferential fiber shortening was reduced (3.82 cm to 2.02 cm), and during ejection the fiber and contractile element velocities were diminished at wall tensions comparable to control; maximal velocity and velocity at peak tension were also decreased. The tension-velocity relation during isovolumic beats was shifted by failure with consistent reductions in maximal shortening velocity, but changes in maximal tension were small. Maximal instantaneous power was always reduced by failure, and a striking alteration occurred in the relation between work expended in stretching the series elastic component and the external work; the former, "internal work," increased by an average of 90%, the latter diminished by 11%, and the total contractile element work remained essentially unchanged. These findings are discussed within the framework of a three dimensional model that included fiber length, wall tension, and contractile element velocity. The experimental techniques employed appear to permit a more complete definition of the abnormalities of the ventricular myocardium in experimental failure. They are potentially applicable in the closed-chest animal and allow quantitative determinations of the contractile properties of the left ventricle.

Effect of Afterload on Force-Velocity Relations and Contractile Element Work in the Intact Dog Heart

The effects of heightened afterload on force-velocity relations and on contractile element work of single systoles were examined in the intact dog heart. The force-velocity curve described during the course of a normal systole represents a composite of curves, each with its own projected isometric force determined by instantaneous changes in fiber length. During the first systole following an afterload intervention, reciprocal changes in force and velocity were observed together with an extension of the projected isometric-force. The effect of afterload on contractile element work was determined by: (1) the direction and magnitude of the afterload, and (2) the afterload of the control beat itself. When the control beat was lightly loaded, an increase in afterload increased contractile element work by two additive mechanisms: (1) an increase in mean isometric force, and (2) a shift of force-velocity relations to positions of greater power and work production. In normally loaded control beats, an increase in afterload resulted in a decrease in contractile element work, despite the fact that mean isometric force was increased. In this instance, force-velocity relations were shifted to positions where less power and work could be achieved. Thus, the normal systole appears to function at the apex of the contractile element work-load curve (near 60% of the isometric load). Evidence is presented which suggests that the apparent maximum active state of the entire left ventricle is generally achieved within 30 to 50 msec after the onset of pressure rise, and that its decay is accompanied by abrupt divergence of the force-velocity relations from the inverse curve of that beat. A sudden increase in afterload does not appear to influence the duration of the maximum active state, although the duration of positive contractile element work is shortened and that of negative contractile element work prolonged.