Adaptive control of cardiac contraction to changes in loading: from theory of sarcomere dynamics to whole-heart function

Yadid, Moran; Sela, Gali; Pavlov, Daria Amiad; Landesberg, Amir

doi:10.1007/s00424-011-0966-x

Cited by 14 publications

(9 citation statements)

References 46 publications

(89 reference statements)

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“…Whereas these results appear to provide prima facie evidence for a direct length‐dependent effect on crossbridge cooperativity, there is now consensus (Gaasch et al 1980; Hofman and Fuchs, 1987; Kurihara & Komukai, 1995; Komukai & Kurihara, 1996; Shimizu et al 2002; Ferenc Édes et al 2007; de Tombe et al 2010; Yadid et al 2011) that the effect of length on twitch duration (Fig. 4) is indirect , secondary to its effect on force.…”

Section: Discussionmentioning

confidence: 92%

Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling

Han

Tran

Taberner

et al. 2012

The Journal of Physiology

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Key points• The energy expenditure of the heart is linearly related to its work performance, as measured by its development of pressure-volume area.• We have explored the basis of this phenomenon both experimentally (by measuring the heat production of isolated ventricular tissue undergoing cyclic contraction and relaxation) and theoretically (using mathematical modelling).• We provide the first evidence that the heat production of isolated trabeculae undergoing fixed-end contractions varies linearly with force-length area, and confirm that twitch duration increases progressively with muscle length.• Mathematical modelling reveals that length-dependent prolongation of the twitch reflects length-(or, equivalently, force-) dependent binding of Ca 2+ to troponin-C, together with Ca 2+ -dependent crossbridge cooperativity.• Mathematical modelling further reveals that the apparent linear dependence of heat production on force-length area is remarkably robust against departures from the linearity of length-dependent twitch duration.Abstract We tested the proposition that linear length dependence of twitch duration underlies the well-characterised linear dependence of oxygen consumption (V O 2 ) on pressure-volume area (PVA) in the heart. By way of experimental simplification, we reduced the problem from three dimensions to one by substituting cardiac trabeculae for the classically investigated whole-heart. This allowed adoption of stress-length area (SLA) as a surrogate for PVA, and heat as a proxy foṙ V O 2 . Heat and stress (force per cross-sectional area), at a range of muscle lengths and at both 1 mM and 2 mM [Ca 2+ ] o , were recorded from continuously superfused rat right-ventricular trabeculae undergoing fixed-end contractions. The heat-SLA relations of trabeculae (reported here, for the first time) are linear. Twitch duration increases monotonically (but not strictly linearly) with muscle length. We probed the cellular mechanisms of this phenomenon by determining: (i) the length dependence of the duration of the Ca 2+ transient, (ii) the length dependence of the rate of force redevelopment following a length impulse (an index of Ca 2+ binding to troponin-C), (iii) the effect on the simulated time course of the twitch of progressive deletion of lengthand Ca 2+ -dependent mechanisms of crossbridge cooperativity, using a detailed mathematical model of the crossbridge cycle, and (iv) the conditions required to achieve these multiple length dependencies, using a greatly simplified model of twitch mechano-energetics. From the results of these four independent investigations, we infer that the linearity of the heat-SLA relation (and, J.-C. Han and K. Tran contributed equally to this work.

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Section: Discussionmentioning

confidence: 92%

Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling

Han

Tran

Taberner

et al. 2012

The Journal of Physiology

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“…Although the a and b Hill equation fit parameters may differ for the various phosphomimetic constructs, we do not draw any conclusions from these differences as investigators in the past have not been able to relate these parameters to any meaningful physiological property of the underlying contractile system (Woledge et al 1985). However, a more recent model proposes that strained myosin attached to a moving actin filament exists in a mechanical feedback loop that depends on the rate of actin filament sliding and that the model provides an analytical basis for the Hill F:V parameters (Yadid et al 2011). …”

Section: Resultsmentioning

confidence: 99%

The extent of cardiac myosin binding protein-C phosphorylation modulates actomyosin function in a graded manner

Weith

Previs

Hoeprich

et al. 2012

J Muscle Res Cell Motil

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Cardiac myosin binding protein-C (cMyBP-C), a sarcomeric protein with 11 domains, C0-C10, binds to the myosin rod via its C-terminus, while its N-terminus binds regions of the myosin head and actin. These N-terminal interactions can be attenuated by phosphorylation of serines in the C1-C2 motif linker. Within the sarcomere, cMyBP-C exists in a range of phosphorylation states, which may affect its ability to regulate actomyosin motion generation. To examine the functional importance of partial phosphorylation, we bacterially expressed N-terminal fragments of cMyBP-C (domains C0-C3) with 3 of its phosphorylatable serines (S273, S282, and S302) mutated in combinations to either aspartic acids or alanines, mimicking phosphorylation and dephosphorylation respectively. The effect of these C0-C3 constructs on actomyosin motility were characterized in both the unloaded in vitro motility assay and in the load-clamped laser trap assay where force:velocity (F:V) relations were obtained. In the motility assay, phosphomimetic replacement (i.e. aspartic acid) reduced the slowing of actin velocity observed in the presence of C0-C3 in proportion to the total number phosphomimetic replacements. Under load, C0-C3 depressed the F:V relationship without any effect on maximal force. Phosphomimetic replacement reversed the depression of F:V by C0-C3 in a graded manner with respect to the total number of replacements. Interestingly, the effect of C0-C3 on F:V was well fitted by a model that assumed C0-C3 acts as an effective viscous load against which myosin must operate. This study suggests that increasing phosphorylation of cMyBP-C incrementally reduces its modulation of actomyosin motion generation providing a tunable mechanism to regulate cardiac function.

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“…The comparisons of echocardiographic data showed the IDH group had notably worse RV systolic function than did the non‐IDH group, detected by 3DSTE. In healthy individuals, compensatory enhancement of myocardial contraction occurred after reduction of preload to maintain adequate cardiac output and blood pressure . Patients in non‐IDH group usually hold better cardiac function and compensatory mechanism.…”

Section: Discussionmentioning

confidence: 99%

Long‐term impacts of hemodialysis on the right ventricle: Assessment via 3‐dimensional speckle‐tracking echocardiography

Sun

Cao

Guo

et al. 2018

Clinical Cardiology

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Background Right ventricular (RV) dysfunction is a major cause of death in patients undergoing maintenance hemodialysis (MHD). We used 3‐dimensional speckle‐tracking echocardiography (3DSTE) to evaluate long‐term impacts of MHD on RV function. Hypothesis In this study, RV dysfunction in MHD patients will be revealed and studied in depth by 3DSTE. Methods Echocardiography was performed on 110 consecutively enrolled individuals: 30 controls and 80 patients with MHD. Conventional echocardiographic parameters and 3DSTE parameters were obtained and compared between groups. Univariate and multivariate logistic regression analysis identified independent predictors of intradialytic hypotension (IDH). Results Compared with the control group, RV end‐diastolic volume (RVEDV) was markedly enlarged (46.1 ± 11.8 mL/m2 vs 42.3 ± 8.6 mL/m2; P = 0.047), whereas RV ejection fraction (RVEF) was significantly lower in the MHD group (50.6% ± 5.8% vs 55.2% ± 3.7%; P < 0.001). RV global, septal, and lateral wall longitudinal strains were also decreased in the MHD group (−18.2 ± 3.6 vs −22.6 ± 4.3%; −13.1 ± 3.8 vs −17.5 ± 5.5%; and −23.4 ± 4.7 vs −27.7 ± 4.0%, respectively; all P < 0.001). RVEF (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51 to 1.01, P = 0.038) and history of diabetes (OR: 11.14, 95% CI: 1.16 to 106.71, P = 0.036) were 2 independent predictors of IDH. Ultrafiltration rate was an independent factor associated with RVEF (β = −0.01, 95% CI: −0.019 to 0.001, P = 0.039). Conclusions RVEF by 3DSTE could be an important predictor of IDH in MHD patients, and lower ultrafiltration rate was protective for RVEF. 3DSTE may have potential in RV evaluation and risk stratification in MHD patients.

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Adaptive control of cardiac contraction to changes in loading: from theory of sarcomere dynamics to whole-heart function

Cited by 14 publications

References 46 publications

Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling

Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling

The extent of cardiac myosin binding protein-C phosphorylation modulates actomyosin function in a graded manner

Long‐term impacts of hemodialysis on the right ventricle: Assessment via 3‐dimensional speckle‐tracking echocardiography

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