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.
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August 2018
Research-Article
Multiscale Computational Analysis of Right Ventricular Mechanoenergetics
Ryan J. Pewowaruk,
Ryan J. Pewowaruk
Mem. ASME
Biomedical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: pewowaruk@wisc.edu
Biomedical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: pewowaruk@wisc.edu
Search for other works by this author on:
Jennifer L. Philip,
Jennifer L. Philip
Surgery,
University of Wisconsin—Madison,
1550 Engineering Drive,
Madison, WI 53706
e-mail: philip@surgery.wisc.edu
University of Wisconsin—Madison,
2143 Engineering Centers Building
,1550 Engineering Drive,
Madison, WI 53706
e-mail: philip@surgery.wisc.edu
Search for other works by this author on:
Shivendra G. Tewari,
Shivendra G. Tewari
Molecular & Integrative Physiology,
University of Michigan—Ann Arbor,
North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: tewarisg@gmail.com
University of Michigan—Ann Arbor,
2800 Plymouth Road
,North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: tewarisg@gmail.com
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Claire S. Chen,
Claire S. Chen
Mechanical Engineering,
University of Wisconsin—Madison,
1550 Engineering Drive,
Madison, WI 53706
e-mail: cchen394@wisc.edu
University of Wisconsin—Madison,
2145 Engineering Centers Building
,1550 Engineering Drive,
Madison, WI 53706
e-mail: cchen394@wisc.edu
Search for other works by this author on:
Mark S. Nyaeme,
Mark S. Nyaeme
Biomedical Engineering,
University of Wisconsin—Madison,
1550 Engineering Drive,
Madison, WI 53706
e-mail: mnyaeme@wisc.edu
University of Wisconsin—Madison,
2145 Engineering Centers Building
,1550 Engineering Drive,
Madison, WI 53706
e-mail: mnyaeme@wisc.edu
Search for other works by this author on:
Zhijie Wang,
Zhijie Wang
Mechanical Engineering,
Colorado State University,
Fort Collins, CO 80521
e-mail: Zhijie.Wang@colostate.edu
Colorado State University,
1301 Campus Delivery
,Fort Collins, CO 80521
e-mail: Zhijie.Wang@colostate.edu
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Diana M. Tabima,
Diana M. Tabima
Biomedical Engineering,
University of Wisconsin—Madison,
1550 Engineering Drive,
Madison, WI 53706
e-mail: dtabimamarti@wisc.edu
University of Wisconsin—Madison,
2144 Engineering Centers Building
,1550 Engineering Drive,
Madison, WI 53706
e-mail: dtabimamarti@wisc.edu
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Anthony J. Baker,
Anthony J. Baker
Medicine,
University of California—San Francisco,
San Francisco, CA 94121;
VA Medical Center,
4150 Clement St.,
San Francisco, CA 94121
e-mail: Anthony.baker@ucsf.edu
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
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Daniel A. Beard,
Daniel A. Beard
Molecular & Integrative Physiology,
University of Michigan—Ann Arbor,
North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: beardda@med.umich.edu
University of Michigan—Ann Arbor,
2800 Plymouth Road
,North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: beardda@med.umich.edu
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Naomi C. Chesler
Naomi C. Chesler
Fellow ASME
Biomedical Engineering,
University of Wisconsin—Madison Medicine,
1550 Engineering Drive,
Madison, WI 53706
e-mail: naomi.chesler@wisc.edu
Biomedical Engineering,
University of Wisconsin—Madison Medicine,
2146 Engineering Centers Building
,1550 Engineering Drive,
Madison, WI 53706
e-mail: naomi.chesler@wisc.edu
Search for other works by this author on:
Ryan J. Pewowaruk
Mem. ASME
Biomedical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: pewowaruk@wisc.edu
Biomedical Engineering,
University of Wisconsin—Madison,
2145 Engineering Centers Building,
1550 Engineering Drive,
Madison, WI 53706
e-mail: pewowaruk@wisc.edu
Jennifer L. Philip
Surgery,
University of Wisconsin—Madison,
1550 Engineering Drive,
Madison, WI 53706
e-mail: philip@surgery.wisc.edu
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,
North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: tewarisg@gmail.com
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,
1550 Engineering Drive,
Madison, WI 53706
e-mail: cchen394@wisc.edu
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,
1550 Engineering Drive,
Madison, WI 53706
e-mail: mnyaeme@wisc.edu
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,
Fort Collins, CO 80521
e-mail: Zhijie.Wang@colostate.edu
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,
1550 Engineering Drive,
Madison, WI 53706
e-mail: dtabimamarti@wisc.edu
University of Wisconsin—Madison,
2144 Engineering Centers Building
,1550 Engineering Drive,
Madison, WI 53706
e-mail: dtabimamarti@wisc.edu
Anthony J. Baker
Medicine,
University of California—San Francisco,
San Francisco, CA 94121;
VA Medical Center,
4150 Clement St.,
San Francisco, CA 94121
e-mail: Anthony.baker@ucsf.edu
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,
North Campus Research Center,
Ann Arbor, MI 48109-5622
e-mail: beardda@med.umich.edu
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,
1550 Engineering Drive,
Madison, WI 53706
e-mail: naomi.chesler@wisc.edu
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. Aug 2018, 140(8): 081001 (15 pages)
Published Online: May 24, 2018
Article history
Received:
December 1, 2017
Revised:
April 13, 2018
Citation
Pewowaruk, R. J., Philip, J. L., Tewari, S. G., Chen, C. S., Nyaeme, M. S., Wang, Z., Tabima, D. M., Baker, A. J., Beard, D. A., and Chesler, N. C. (May 24, 2018). "Multiscale Computational Analysis of Right Ventricular Mechanoenergetics." ASME. J Biomech Eng. August 2018; 140(8): 081001. https://doi.org/10.1115/1.4040044
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