Regulation of energy consumption in cardiac muscle: analysis of isometric contractions

1999 ◽  
Vol 276 (3) ◽  
pp. H998-H1011 ◽  
Author(s):  
Amir Landesberg ◽  
Samuel Sideman

The well-known linear relationship between oxygen consumption and force-length area or the force-time integral is analyzed here for isometric contractions. The analysis, which is based on a biochemical model that couples calcium kinetics with cross-bridge cycling, indicates that the change in the number of force-generating cross bridges with the change in the sarcomere length depends on the force generated by the cross bridges. This positive-feedback phenomenon is consistent with our reported cooperativity mechanism, whereby the affinity of the troponin for calcium and, hence, cross-bridge recruitment depends on the number of force-generating cross bridges. Moreover, it is demonstrated that a model that does not include a feedback mechanism cannot describe the dependence of energy consumption on the loading conditions. The cooperativity mechanism, which has been shown to determine the force-length relationship and the related Frank-Starling law, is shown here to provide the basis for the regulation of energy consumption in the cardiac muscle.

1988 ◽  
Vol 255 (4) ◽  
pp. C536-C542 ◽  
Author(s):  
J. S. Walker ◽  
I. R. Wendt ◽  
C. L. Gibbs

Heat production, unloaded shortening velocity (Vus), and load-bearing capacity (LBC) were studied in the isolated rat anococcygeus muscle during isometric contractions at 27 degrees C. The relation between the total suprabasal heat produced and the stress-time integral for isometric contractions of various durations was curvilinear, demonstrating a decreasing slope as contractile duration increased. The rate of heat production at 600 s was approximately 68% of the peak value of 6.55 mW/g that occurred at 10 s. At the same time, force rose from a mean of 92 mN/mm2 at 10 s to a value of 140 mN/mm2 at 600 s. This produced a nearly threefold increase in the economy of force maintenance. The decline in the rate of heat production was accompanied by a decline in Vus from 0.56 Lo/s at 10 s to 0.28 Lo/s at 600 s, where Lo is the length for optimal force development. This suggests the fall in the rate of heat production was caused, at least in part, by a slowing of cross-bridge kinetics. The ratio of LBC to developed tension at 10 s was not significantly different from the ratio at 600 s, suggesting that the increase in tension was due to an increased number of attached cross bridges. The decline in heat production, therefore, appears contradictory, since an increased number of attached cross bridges would predict an increased rate of energy expenditure. The observations can be reconciled if either 1) the increase in force is caused by a progressive increase in the attachment time of a constant number of cross bridges that cycle at a lower frequency or 2) the decline in energy expenditure caused by the slowing of cross-bridge cycling is sufficient to mask the increase caused by the recruitment of additional cross bridges.


1994 ◽  
Vol 266 (3) ◽  
pp. H1047-H1054 ◽  
Author(s):  
A. Higashiyama ◽  
M. W. Watkins ◽  
Z. Chen ◽  
M. M. LeWinter

Myocardial energy consumption for nonmechanical activity (excitation-contraction coupling) has been shown to be length dependent in isolated muscle studies but no more than minimally affected by preload in the whole heart. However, unloaded O2 consumption (VO2, which is used to estimate nonmechanical VO2 in whole heart) may not be accurate for quantifying nonmechanical energy consumption, because it contains VO2 for residual cross-bridge cycling. To more accurately determine the influence of left ventricular (LV) diastolic volume on nonmechanical VO2 in whole heart, we employed a new method for quantifying nonmechanical VO2, using the drug 2,3-butanedione monoxime (BDM). We measured VO2 and force-time integral during infusion of BDM (< or = 5 mM) at high (VH) and low LV volumes (VL) in 16 excised isovolumically contracting red blood cell-perfused rabbit ventricles. LV end-diastolic pressure was 9.7 +/- 4.6 and 3.8 +/- 2.8 (SD) mmHg at VH and VL, respectively. Nonmechanical VO2, estimated as the VO2-axis intercept of the linear VO2-force-time integral relation obtained during BDM infusion, did not differ significantly between VH and VL (0.0137 +/- 0.0083 and 0.0132 +/- 0.0090 ml O2.beat-1 x 100 gLV-1, P = 0.702). A multiple linear regression analysis for the pooled data confirmed this finding (P = 0.361). We conclude that, in the rabbit heart, LV diastolic volume does not importantly affect nonmechanical energy consumption over a physiological range of LV end-diastolic pressure. This indicates that length-dependent activation does not have an energetic cost in whole rabbit heart and suggests that its predominant mechanism is increased Ca2+ affinity for the contractile proteins.


1993 ◽  
Vol 26 (10) ◽  
pp. 1217-1225 ◽  
Author(s):  
Tad W. Taylor ◽  
Yoichi Goto ◽  
Katsuya Hata ◽  
Toshiyuki Takasago ◽  
Akio Saeki ◽  
...  

1994 ◽  
Vol 266 (3) ◽  
pp. H1260-H1271 ◽  
Author(s):  
A. Landesberg ◽  
S. Sideman

This study examines the coupling of calcium binding to troponin with the force developed by the cross bridges in the skinned cardiac muscle. It emphasizes the key role of the troponin complex in regulating cross-bridge cycling and defines four distinct states of the troponin complex in the single-overlap region. These include a "loose-coupling" state, wherein cross bridges can exist in the strong conformation without having calcium bound to the neighbor troponin C. Published simultaneous measurements of the force and the bound calcium are used to calculate the apparent calcium binding coefficients. The force-length relationships at different free calcium concentrations are used to evaluate the cooperative mechanism. The dependence of the affinity of troponin for calcium on the number of force-generating cross bridges is the dominant cooperative mechanism. The proposed loose-coupling model, with a positive feedback of force on calcium binding, describes the role of calcium in force regulation and the force-length relationship in skinned cardiac muscle. The ability to simulate the rate of force development is demonstrated.


1987 ◽  
Vol 253 (1) ◽  
pp. C90-C96 ◽  
Author(s):  
P. A. Hofmann ◽  
F. Fuchs

The sensitivity of skinned cardiac muscle bundles to Ca2+ is a function of sarcomere length. Ca2+ sensitivity is increased as fiber length is extended along the ascending limb of the force-length curve and it has been suggested that this phenomenon makes a major contribution to the steep force-length relationship that exists in living cardiac muscle. To gain greater insight into the mechanism behind the length dependence of Ca2+ sensitivity isotopic measurements of Ca2+ binding to detergent-extracted bovine, ventricular muscle bundles were made under conditions in which troponin C was the only major Ca2+ binding species. Experiments were designed to determine whether 1) Ca2+-troponin C affinity varies in the sarcomere length range corresponding to the ascending limb of the force-length curve, and 2) Ca2+ binding correlates with length per se or with changes in the number of length-dependent cross-bridge attachments. Measurements were made of Ca2+ binding in the rigor and relaxed states. The latter state was produced by suppressing actin-myosin interaction with the phosphate analogue, sodium vanadate. After vanadate treatment it is possible to obtain a complete Ca2+ saturation curve in the presence of physiological MgATP concentrations and at constant sarcomere length. The results show that the binding of Ca2+ to the regulatory site of cardiac troponin C is length dependent but this length dependence is actually a dependence on the number of attached cross bridges.


1987 ◽  
Vol 60 (6) ◽  
pp. 797-803 ◽  
Author(s):  
H Suga ◽  
Y Goto ◽  
T Nozawa ◽  
Y Yasumura ◽  
S Futaki ◽  
...  

Author(s):  
A. De Haan ◽  
J. E. Van Doorn ◽  
P. A. Huijing ◽  
R. D. Woittiez ◽  
H. G. Westra

2002 ◽  
Vol 87 (5) ◽  
pp. 2271-2278 ◽  
Author(s):  
Lisa Griffin ◽  
Sharlene Godfrey ◽  
Christine K. Thomas

The pattern of seven pulses that elicited maximal thenar force was determined for control muscles and those that have been paralyzed chronically by spinal cord injury. For each subject group ( n = 6), the peak force evoked by two pulses occurred at a short interval (5–15 ms; a “doublet”), but higher mean relative forces were achieved in paralyzed versus control muscles (41.4 ± 3.9% vs. 22.7 ± 2.0% maximal). Thereafter, longer intervals evoked peak force in each type of muscle (mean: 35 ± 1 ms, 36 ± 2 ms, respectively). With seven pulses, paralyzed and control muscles reached 76.4 ± 5.6% and 57.0 ± 2.6% maximal force, respectively. These force differences resulted from significantly greater doublet/twitch and doublet/tetanic force ratios in paralyzed (2.73 ± 0.08, 0.35 ± 0.03) compared with control muscles (2.07 ± 0.07, 0.25 ± 0.01). The greater force enhancement produced in paralyzed muscles with two closely spaced pulses may relate to changes in muscle stiffness and calcium metabolism. Peak force-time integrals were also achieved with an initial short interpulse interval, followed by longer intervals. The postdoublet intervals that produced peak force-time integrals in paralyzed and control muscles were longer than those for peak force, however (77 ± 3 ms, 95 ± 4 ms, respectively). These data show that the pulse patterns that maximize force and force-time integral in paralyzed muscles are similar to those that maximize these parameters in single motor units and various whole muscles across species. Thus the changes in neuromuscular properties that occur with chronic paralysis do not strongly influence the pulse pattern that optimizes muscle force or force-time integral.


2002 ◽  
Vol 283 (1) ◽  
pp. H324-H330 ◽  
Author(s):  
Jeffrey W. Holmes ◽  
Mark Hünlich ◽  
Gerd Hasenfuss

We tested the hypothesis that economy and efficiency are independent of length in intact cardiac muscle over its normal working range. We measured force, force-time integral, force-length area, and myocardial oxygen consumption in eight isometrically contracting rabbit right ventricular papillary muscles. 2,3-Butanedione monoxime was used to partition nonbasal oxygen consumption into tension-independent and tension-dependent components. Developed force, force-time integral, and force-length area increased by factors of 2.4, 2.7, and 4.8, respectively, as muscle length was increased from 90% to 100% maximal length, whereas tension-dependent oxygen consumption increased only 1.6-fold. Economy (the ratio of force-time integral to tension-dependent oxygen consumption) increased significantly with muscle length, as did contractile efficiency, the ratio of force-length area to tension-dependent oxygen consumption. The average force-length area-nonbasal oxygen consumption intercept was more than the twice tension-independent oxygen consumption. We conclude that economy and efficiency increase with length in rabbit myocardium. This conclusion is consistent with published data in isolated rabbit and dog hearts but at odds with studies in skinned myocardium.


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