Research Papers

Multiscale Computational Analysis of Right Ventricular Mechanoenergetics

[+] Author and Article Information
Ryan J. Pewowaruk

Biomedical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: pewowaruk@wisc.edu

Jennifer L. Philip

University of Wisconsin—Madison,
2143 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: philip@surgery.wisc.edu

Shivendra G. Tewari

Molecular & Integrative Physiology,
University of Michigan—Ann Arbor,
2800 Plymouth Road,
North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: tewarisg@gmail.com

Claire S. Chen

Mechanical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: cchen394@wisc.edu

Mark S. Nyaeme

Biomedical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: mnyaeme@wisc.edu

Zhijie Wang

Mechanical Engineering,
Colorado State University,
1301 Campus Delivery,
Fort Collins, CO 80521
e-mail: Zhijie.Wang@colostate.edu

Diana M. Tabima

Biomedical Engineering,
University of Wisconsin—Madison,
2144 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: dtabimamarti@wisc.edu

Anthony J. Baker

University of California—San Francisco,
4150 Clement St,
San Francisco, CA 94121;
VA Medical Center,
4150 Clement St.,
San Francisco, CA 94121
e-mail: Anthony.baker@ucsf.edu

Daniel A. Beard

Molecular & Integrative Physiology,
University of Michigan—Ann Arbor,
2800 Plymouth Road,
North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: beardda@med.umich.edu

Naomi C. Chesler

Fellow ASME
Biomedical Engineering,
University of Wisconsin—Madison Medicine,
2146 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: naomi.chesler@wisc.edu

1Corresponding author.

Manuscript received December 1, 2017; final manuscript received April 13, 2018; published online May 24, 2018. Assoc. Editor: Rouzbeh Amini.

J Biomech Eng 140(8), 081001 (May 24, 2018) (15 pages) Paper No: BIO-17-1562; doi: 10.1115/1.4040044 History: Received December 01, 2017; Revised April 13, 2018

Right ventricular (RV) failure, which occurs in the setting of pressure overload, is characterized by abnormalities in mechanical and energetic function. The effects of these cell- and tissue-level changes on organ-level RV function are unknown. The primary aim of this study was to investigate the effects of myofiber mechanics and mitochondrial energetics on organ-level RV function in the context of pressure overload using a multiscale model of the cardiovascular system. The model integrates the mitochondria-generated metabolite concentrations that drive intracellular actin-myosin cross-bridging and extracellular myocardial tissue mechanics in a biventricular heart model coupled with simple lumped parameter circulations. Three types of pressure overload were simulated and compared to experimental results. The computational model was able to capture a wide range of cardiovascular physiology and pathophysiology from mild RV dysfunction to RV failure. Our results confirm that, in response to pressure overload alone, the RV is able to maintain cardiac output (CO) and predict that alterations in either RV active myofiber mechanics or RV metabolite concentrations are necessary to decrease CO.

Copyright © 2018 by ASME
Your Session has timed out. Please sign back in to continue.


Hosenpud, J. D. , Bennett, L. E. , Keck, B. M. , Boucek, M. M. , and Novick, R. J. , 2000, “ The Registry of the International Society for Heart and Lung Transplantation: Seventeenth Official Report-2000,” J. Heart. Lung Transplant., 19(10), pp. 909–931. [CrossRef] [PubMed]
Ghio, S. , Gavazzi, A. , Campana, C. , Inserra, C. , Klersy, C. , Sebastiani, R. , Arbustini, E. , Recusani, F. , and Tavazzi, L. , 2001, “ Independent and Additive Prognostic Value of Right Ventricular Systolic Function and Pulmonary Artery Pressure in Patients With Chronic Heart Failure,” J. Am. Coll. Cardiol., 37(1), pp. 183–188. [CrossRef] [PubMed]
Friedberg, M. K. , and Redington, A. N. , 2014, “ Right Versus Left Ventricular Failure: Differences, Similarities, and Interactions,” Circulation, 129(9), pp. 1033–1044. [CrossRef] [PubMed]
Vonk Noordegraaf, A. , and Galie, N. , 2011, “ The Role of the Right Ventricle in Pulmonary Arterial Hypertension,” Eur. Respir. Rev., 20(122), pp. 243–253. [CrossRef] [PubMed]
Sztrymf, B. , Souza, R. , Bertoletti, L. , Jaïs, X. , Sitbon, O. , Price, L. C. , Simonneau, G. , and Humbert, M. , 2010, “ Prognostic Factors of Acute Heart Failure in Patients With Pulmonary Arterial Hypertension,” Eur. Respir. J., 35(6), pp. 1286–1293. [CrossRef] [PubMed]
Tewari, S. G. , Bugenhagen, S. M. , Vinnakota, K. C. , Rice, J. J. , Janssen, P. M. L. , and Beard, D. A. , 2016, “ Influence of Metabolic Dysfunction on Cardiac Mechanics in Decompensated Hypertrophy and Heart Failure,” J. Mol. Cell Cardiol., 94, pp. 162–175. [CrossRef] [PubMed]
Bers, D. M. , 2000, “ Calcium Fluxes Involved in Control of Cardiac Myocyte Contraction,” Circ. Res., 87(4), pp. 275–281. [CrossRef] [PubMed]
Ventura-Clapier, R. , Garnier, A. , Veksler, V. , and Joubert, F. , 2011, “ Bioenergetics of the Failing Heart,” Biochim. Biophys. Acta, 1813(7), pp. 1360–1372. [CrossRef] [PubMed]
Golob, M. , Moss, R. L. , and Chesler, N. C. , 2014, “ Cardiac Tissue Structure, Properties, and Performance: A Materials Science Perspective,” Ann. Biomed. Eng., 42(10), pp. 2003–2013. [CrossRef] [PubMed]
Tabima, D. M. , Philip, J. L. , and Chesler, N. C. , 2017, “ Right Ventricular-Pulmonary Vascular Interactions,” Physiol. (Bethesda), 32(5), pp. 346–356.
Buckberg, G. , Mahajan, A. , Saleh, S. , Hoffman, J. I. , and Coghlan, C. , 2008, “ Structure and Function Relationships of the Helical Ventricular Myocardial Band,” J. Thorac. Cardiovasc. Surg., 136(3), pp. 578–589. [CrossRef] [PubMed]
Liu, A. , Philip, J. , Vinnakota, K. C. , Van den Bergh, F. , Tabima, D. M. , Hacker, T. , Beard, D. A. , and Chesler, N. C. , 2017, “ Estrogen Maintains Mitochondrial Content and Function in the Right Ventricle of Rats With Pulmonary Hypertension,” Physiol. Rep., 5(6), p. e13157. [CrossRef] [PubMed]
Gomez-Arroyo, J. , Mizuno, S. , Szczepanek, K. , Van Tassell, B. , Natarajan, R. , dos Remedios, C. G. , Drake, J. I. , Farkas, L. , Kraskauskas, D. , Wijesinghe, D. S. , Chalfant, C. E. , Bigbee, J. , Abbate, A. , Lesnefsky, E. J. , Bogaard, H. J. , and Voelkel, N. F. , 2013, “ Metabolic Gene Remodeling and Mitochondrial Dysfunction in Failing Right Ventricular Hypertrophy Secondary to Pulmonary Arterial Hypertension,” Circ. Heart Fail., 6(1), pp. 136–144. [CrossRef] [PubMed]
Bache, R. J. , Zhang, J. , Murakami, Y. , Zhang, Y. , Cho, Y. K. , Merkle, H. , Gong, G. , From, A. H. , and Ugurbil, K. , 1999, “ Myocardial Oxygenation at High Workstates in Hearts With Left Ventricular Hypertrophy,” Cardiovasc. Res., 42(3), pp. 616–626. [CrossRef] [PubMed]
Cowley, P. M. , Wang, G. Y. , Joshi, S. K. , Swigart, P. M. , Lovett, D. H. , Simpson, P. C. , and Baker, A. J. , 2017, “ α1A-Subtype Adrenergic Agonist Therapy for Failing Right Ventricle,” Am. J. Physiol. Heart Circ. Physiol., 313(6), pp. H1109–H1118.
Wang, G. Y. , Yeh, C. C. , Jensen, B. C. , Mann, M. J. , Simpson, P. C. , and Baker, A. J. , 2010, “ Heart Failure Switches the RV α1-Adrenergic Inotropic Response From Negative to Positive,” Am. J. Physiol. Heart Circ. Physiol., 298(3), pp. H913–H920. [CrossRef] [PubMed]
Rain, S. , Andersen, S. , Najafi, A. , Gammelgaard Schultz, J. , da Silva Goncalves Bos, D. , Handoko, M. L. , Bogaard, H. J. , Vonk-Noordegraaf, A. , Andersen, A. , van der Velden, J. , Ottenheijm, C. A. , and de Man, F. S. , 2016, “ Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness,” Circ. Heart Fail., 9(7), pp. 1–9.
Wang, Z. , Patel, J. R. , Schreier, D. A. , Hacker, T. A. , Moss, R. L. , and Chesler, N. C. , 2018, “ Organ-Level Right Ventricular Dysfunction With Preserved Frank-Starling Mechanism in a Mouse Model of Pulmonary Arterial Hypertension,” J. Appl. Physiol., (epub).
Bogaard, H. J. , Natarajan, R. , Henderson, S. C. , Long, C. S. , Kraskauskas, D. , Smithson, L. , Ockaili, R. , McCord, J. M. , and Voelkel, N. F. , 2009, “ Chronic Pulmonary Artery Pressure Elevation is Insufficient to Explain Right Heart Failure,” Circulation, 120(20), pp. 1951–1960. [CrossRef] [PubMed]
Drake, J. I. , Bogaard, H. J. , Mizuno, S. , Clifton, B. , Xie, B. , Gao, Y. , Dumur, C. I. , Fawcett, P. , Voelkel, N. F. , and Natarajan, R. , 2011, “ Molecular Signature of a Right Heart Failure Program in Chronic Severe Pulmonary Hypertension,” Am. J. Respir. Cell Mol. Biol., 45(6), pp. 1239–1247. [CrossRef] [PubMed]
Rain, S. , Handoko, M. L. , Vonk Noordegraaf, A. , Bogaard, H. J. , van der Velden, J. , and de Man, F. S. , 2014, “ Pressure-Overload-Induced Right Heart Failure,” Pflugers Arch., 466(6), pp. 1055–1063. [PubMed]
Vanderpool, R. R. , Pinsky, M. R. , Naeije, R. , Deible, C. , Kosaraju, V. , Bunner, C. , Mathier, M. A. , Lacomis, J. , Champion, H. C. , and Simon, M. A. , 2015, “ RV-Pulmonary Arterial Coupling Predicts Outcome in Patients Referred for Pulmonary Hypertension,” Heart, 101(1), pp. 37–43. [CrossRef] [PubMed]
Territo, P. R. , French, S. A. , and Balaban, R. S. , 2001, “ Simulation of Cardiac Work Transitions, In Vitro: Effects of Simultaneous Ca2+ and ATPase Additions on Isolated Porcine Heart Mitochondria,” Cell Calcium, 30(1), pp. 19–27. [CrossRef] [PubMed]
Bazil, J. N. , Beard, D. A. , and Vinnakota, K. C. , 2016, “ Catalytic Coupling of Oxidative Phosphorylation, ATP Demand, and Reactive Oxygen Species Generation,” Biophys. J., 110(4), pp. 962–971. [CrossRef] [PubMed]
Zahalak, G. I. , 1986, “ A Comparison of the Mechanical Behavior of the Cat Soleus Muscle With a Distribution-Moment Model,” ASME J. Biomech. Eng., 108(2), pp. 131–140. [CrossRef]
Rice, J. J. , Wang, F. , Bers, D. M. , and de Tombe, P. P. , 2008, “ Approximate Model of Cooperative Activation and Crossbridge Cycling in Cardiac Muscle Using Ordinary Differential Equations,” Biophys. J., 95(5), pp. 2368–2390. [CrossRef] [PubMed]
Tran, K. , Smith, N. P. , Loiselle, D. S. , and Crampin, E. J. , 2010, “ A Metabolite-Sensitive, Thermodynamically Constrained Model of Cardiac Cross-Bridge Cycling: Implications for Force Development During Ischemia,” Biophys. J., 98(2), pp. 267–276. [CrossRef] [PubMed]
Tewari, S. G. , Bugenhagen, S. M. , Palmer, B. M. , and Beard, D. A. , 2016, “ Dynamics of Cross-Bridge Cycling, ATP Hydrolysis, Force Generation, and Deformation in Cardiac Muscle,” J. Mol. Cell Cardiol., 96, pp. 11–25. [CrossRef] [PubMed]
Lumens, J. , Delhaas, T. , Kirn, B. , and Arts, T. , 2009, “ Three-Wall Segment (TriSeg) Model Describing Mechanics and Hemodynamics of Ventricular Interaction,” Ann. Biomed. Eng., 37(11), pp. 2234–2255. [CrossRef] [PubMed]
Ben Driss, A. , Devaux, C. , Henrion, D. , Duriez, M. , Thuillez, C. , Levy, B. I. , and Michel, J. B. , 2000, “ Hemodynamic Stresses Induce Endothelial Dysfunction and Remodeling of Pulmonary Artery in Experimental Compensated Heart Failure,” Circulation, 101(23), pp. 2764–2770. [CrossRef] [PubMed]
Hemnes, A. R. , Zaiman, A. , and Champion, H. C. , 2008, “ PDE5A Inhibition Attenuates Bleomycin-Induced Pulmonary Fibrosis and Pulmonary Hypertension Through Inhibition of ROS Generation and RhoA/Rho Kinase Activation,” Am. J. Physiol. Lung Cell Mol. Physiol., 294(1), pp. L24–L33. [CrossRef] [PubMed]
Liu, A. , Tian, L. , Golob, M. , Eickhoff, J. C. , Boston, M. , and Chesler, N. C. , 2015, “ 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension,” Hypertens., 66(5), pp. 1082–1088. [CrossRef]
Jasmin, J. F. , Mercier, I. , Hnasko, R. , Cheung, M. W. , Tanowitz, H. B. , Dupuis, J. , and Lisanti, M. P. , 2004, “ Lung Remodeling and Pulmonary Hypertension After Myocardial Infarction: Pathogenic Role of Reduced Caveolin Expression,” Cardiovasc. Res., 63(4), pp. 747–755. [CrossRef] [PubMed]
Zhang, Y. , Barocas, V. H. , Berceli, S. A. , Clancy, C. E. , Eckmann, D. M. , Garbey, M. , Kassab, G. S. , Lochner, D. R. , McCulloch, A. D. , Tran-Son-Tay, R. , and Trayanova, N. A. , 2016, “ Multi-Scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention,” Ann. Biomed. Eng., 44(9), pp. 2642–2660. [CrossRef] [PubMed]
Kerckhoffs, R. C. , Campbell, S. G. , Flaim, S. N. , Howard, E. J. , Sierra-Aguado, J. , Mulligan, L. J. , and McCulloch, A. D. , 2009, “ Multi-Scale Modeling of Excitation-Contraction Coupling in the Normal and Failing Heart,” IEEE Engineering in Medicine and Biology Society (EMBC), Minneapolis, MN, Sept. 3–6, pp. 4281–4282.
Garbey, M. , Rahman, M. , and Berceli, S. A. , 2015, “ A Multiscale Computational Framework to Understand Vascular Adaptation,” J. Comput. Sci., 8, pp. 32–47. [CrossRef] [PubMed]
Golob, M. J. , Wang, Z. , Prostrollo, A. J. , Hacker, T. A. , and Chesler, N. C. , 2016, “ Limiting Collagen Turnover Via Collagenase-Resistance Attenuates Right Ventricular Dysfunction and Fibrosis in Pulmonary Arterial Hypertension,” Physiol. Rep., 4(11), p. e12815.
Lahm, T. , Frump, A. L. , Albrecht, M. E. , Fisher, A. J. , Cook, T. G. , Jones, T. J. , Yakubov, B. , Whitson, J. , Fuchs, R. K. , Liu, A. , Chesler, N. C. , and Brown, M. B. , 2016, “ 17β-Estradiol Mediates Superior Adaptation of Right Ventricular Function to Acute Strenuous Exercise in Female Rats With Severe Pulmonary Hypertension,” Am. J. Physiol. Lung Cell Mol. Physiol., 311(2), pp. L375–L388. [PubMed]
Costandi, P. N. , Frank, L. R. , McCulloch, A. D. , and Omens, J. H. , 2006, “ Role of Diastolic Properties in the Transition to Failure in a Mouse Model of the Cardiac Dilatation,” Am. J. Physiol. Heart Circ. Physiol., 291(6), pp. H2971–H2979. [CrossRef] [PubMed]
Hill, M. R. , Simon, M. A. , Valdez-Jasso, D. , Zhang, W. , Champion, H. C. , and Sacks, M. S. , 2014, “ Structural and Mechanical Adaptations of Right Ventricle Free Wall Myocardium to Pressure Overload,” Ann. Biomed. Eng., 42(12), pp. 2451–2465. [CrossRef] [PubMed]
Avazmohammadi, R. , Hill, M. R. , Simon, M. A. , Zhang, W. , and Sacks, M. S. , 2017, “ A Novel Constitutive Model for Passive Right Ventricular Myocardium: Evidence for Myofiber-Collagen Fiber Mechanical Coupling,” Biomech. Model. Mechanobiol., 16(2), pp. 561–581. [CrossRef] [PubMed]
Wu, F. , Zhang, E. Y. , Zhang, J. , Bache, R. J. , and Beard, D. A. , 2008, “ Phosphate Metabolite Concentrations and ATP Hydrolysis Potential in Normal and Ischaemic Hearts,” J. Physiol., 586(17), pp. 4193–4208. [CrossRef] [PubMed]
Wu, F. , Zhang, J. , and Beard, D. A. , 2009, “ Experimentally Observed Phenomena on Cardiac Energetics in Heart Failure Emerge From Simulations of Cardiac Metabolism,” Proc. Natl. Acad. Sci. U. S. A., 106(17), pp. 7143–7148. [CrossRef] [PubMed]
Palmer, B. M. , 2010, “ A Strain-Dependency of Myosin Off-Rate Must be Sensitive to Frequency to Predict the B-Process of Sinusoidal Analysis,” Adv. Exp. Med. Biol., 682, pp. 57–75. [CrossRef] [PubMed]
Lu, K. , Clark, J. W. , Ghorbel, F. H. , Ware, D. L. , and Bidani, A. , 2001, “ A Human Cardiopulmonary System Model Applied to the Analysis of the Valsalva Maneuver,” Am. J. Physiol. Heart Circ. Physiol., 281(6), pp. H2661–H2679. [CrossRef] [PubMed]
Charbonneau, P. , 2002, “ An Introduction to Genetic Algorithms for Numerical Optimization,” National Center for Atmospheric Research, Boulder, CO, Technical Note https://www.researchgate.net/publication/228608597_An_Introduction_to_Genetic_Algorithms_for_Numerical_Optimization
Gordon, A. M. , Huxley, A. F. , and Julian, F. J. , 1966, “ The Variation in Isometric Tension With Sarcomere Length in Vertebrate Muscle Fibres,” J. Physiol., 184(1), pp. 170–192. [CrossRef] [PubMed]
Niederer, S. A. , Hunter, P. J. , and Smith, N. P. , 2006, “ A Quantitative Analysis of Cardiac Myocyte Relaxation: A Simulation Study,” Biophys. J., 90(5), pp. 1697–722. [CrossRef] [PubMed]
Reil, J. C. , Hohl, M. , Selejan, S. , Lipp, P. , Drautz, F. , Kazakow, A. , Münz, B. M. , Müller, P. , Steendijk, P. , Reil, G. H. , Allessie, M. A. , Böhm, M. , and Neuberger, H. R. , 2012, “ Aldosterone Promotes Atrial Fibrillation,” Eur. Heart J., 33(16), pp. 2098–2108. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 2

Good agreement is observed between experimental [15] and simulated myofilament force versus pCa2+, especially at maximum myofilament force

Grahic Jump Location
Fig. 1

Schematic of mechanoenergetic computational model of the cardiovascular system adapted from Tewari et al. [6]. (a) Overall scheme. At the cellular level, release of calcium from the sarcoplasmic reticulum and metabolites ATP, ADP, and inorganic phosphates (Pi) drives actin-myosin cross-bridge kinetics, which drives myofiber mechanics dependent on sarcomere length. At the tissue level, myofiber mechanics that incorporate cross-bridge cycling, intracellular titin, and extracellular collagen and generate myofiber stress dependent on myofiber strain. At the organ level, ventricle mechanics and intraventricular interactions drive ventricular pressures dependent on ventricular volumes; the circulation provides ventricular afterload and the hemodynamic connection between the chambers. (b) Diagram of actin-myosin cross-bridging kinetics. Kinetic rates are functions of Ca2+ and metabolite concentrations. (c) Diagram of myofiber mechanics; Fpas: passive force, including contributions of titin and collagen, Fact: active force of actin-myosin cross-bridging, μ: viscous force, and FSE: corrective factor for sarcomere length. (d) Diagram of heart and circulation; C: compliance, R: Resistance, PA: pulmonary artery, PV: pulmonary veins, SV: systemic veins, Ao: aorta, sys: systemic vasculature, pul: pulmonary vasculature, RA: right atria, RV: right ventricle, LA: left atria, and LV: left ventricle.

Grahic Jump Location
Fig. 3

Comparison of Bleo experimental [31] and simulated PH. Error bars represent interquartile range. ((a)–(c)) Simulation predicts preserved Ees until metabolites or maximum force changes, and that maximum force and metabolite changes result in further VVC decreases compared to PH alone. ((d)–(f)) PH alone and PH + increased RV stiffness overestimate RVSP and CO but match EF, while changing maximum force and metabolites matches CO but underestimates RVSP and EF.

Grahic Jump Location
Fig. 4

Comparison of HySu experimental [16] and simulated PH. Error bars represent standard error. PH alone and PH + increased RV stiffness match all hemodynamic parameters well, but changing metabolite concentration and maximum force causes more severe decreases in RV function than observed experimentally.

Grahic Jump Location
Fig. 5

Comparison of MI experimental [30,33] and simulated PH-LHD. Error bars represent standard error. (a) LVSP is maintained in both experiments [30] and simulation. (b) LV EF is predicted to decrease slightly with LHD (HF metabolites in the LV). (c) LV EDP increase is not as severe in simulation as experiment [33]. (d) Simulations predict increased RV afterload, (e) while changing RV metabolites or myofilament force is necessary to decrease Ees, thus (f) VVC is predicted to decrease with LHD, and further decrease with impaired RV cellular function. (g) LHD alone overestimates RVSP, while changing myofilament force and metabolites slightly underestimates RVSP [30]. (h) CO is maintained both experimentally [30] and in simulation. (i) Simulations predict decreased RV EF.

Grahic Jump Location
Fig. 7

EDPVR increases with RV dilation and increased RV stiffness decreases CO but not EDPVR. (a) Pressure overload increases RV end diastolic volume, (b) which results in increased EDPVR, (c) increasing RV stiffness decreases CO, (d) but instead of increasing EDPVR, increased RV stiffness decreases EDPVR. (e) With increased afterload, RV sarcomeres are elongated, and increased stiffness prevents this elongation. (f) With increased afterload, RV passive stress increases, and increasing RV stiffness further increases RV passive stress.

Grahic Jump Location
Fig. 6

Parameter study correlating RV EF with myofilament force and metabolite concentration. (a) At 1x PVR, maximum myofilament force has a much stronger correlation with EF than (b) metabolite concentration has with EF. (c) At 2× PVR, maximum myofilament force still exhibits a stronger correlation with EF than (d) the correlation between metabolite concentration and EF. E. At 4× PVR, maximum myofilament force exhibits a similar correlation with EF as (f) the correlation between metabolite concentration and EF.

Grahic Jump Location
Fig. 8

Plot of time varying atrial compliance. When compliance is low, the atrium is contracting, and when compliance is high, the atrium is relaxed.



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In