Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts
The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remode...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-02-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2018.00037/full |
| _version_ | 1819264012942049280 |
|---|---|
| author | Alexandre Lewalle Sander Land Eric Carruth Lawrence R. Frank Pablo Lamata Jeffrey H. Omens Jeffrey H. Omens Andrew D. McCulloch Andrew D. McCulloch Steven A. Niederer Nicolas P. Smith Nicolas P. Smith |
| author_facet | Alexandre Lewalle Sander Land Eric Carruth Lawrence R. Frank Pablo Lamata Jeffrey H. Omens Jeffrey H. Omens Andrew D. McCulloch Andrew D. McCulloch Steven A. Niederer Nicolas P. Smith Nicolas P. Smith |
| author_sort | Alexandre Lewalle |
| collection | DOAJ |
| description | The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance) to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF) of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks). Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy) and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%), rather than on anatomical features (average decrease ~60%), to achieve compensation of pump function in the early phase of heart failure. |
| first_indexed | 2024-12-23T20:22:43Z |
| format | Article |
| id | doaj.art-72fcf707dccf43d59216548c75c165a4 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-23T20:22:43Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-72fcf707dccf43d59216548c75c165a42022-12-21T17:32:29ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-02-01910.3389/fphys.2018.00037313470Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat HeartsAlexandre Lewalle0Sander Land1Eric Carruth2Lawrence R. Frank3Pablo Lamata4Jeffrey H. Omens5Jeffrey H. Omens6Andrew D. McCulloch7Andrew D. McCulloch8Steven A. Niederer9Nicolas P. Smith10Nicolas P. Smith11Department of Biomedical Engineering, King's College London, St. Thomas's Hospital, London, United KingdomDepartment of Biomedical Engineering, King's College London, St. Thomas's Hospital, London, United KingdomDepartment of Bioengineering, University of California, San Diego, San Diego, CA, United StatesRadiology Department, University of California, San Diego, San Diego, CA, United StatesDepartment of Biomedical Engineering, King's College London, St. Thomas's Hospital, London, United KingdomDepartment of Bioengineering, University of California, San Diego, San Diego, CA, United StatesDepartment of Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Bioengineering, University of California, San Diego, San Diego, CA, United StatesDepartment of Medicine, University of California, San Diego, La Jolla, CA, United StatesDepartment of Biomedical Engineering, King's College London, St. Thomas's Hospital, London, United KingdomDepartment of Biomedical Engineering, King's College London, St. Thomas's Hospital, London, United KingdomFaculty of Engineering, University of Auckland, Auckland, New ZealandThe cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance) to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF) of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks). Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy) and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%), rather than on anatomical features (average decrease ~60%), to achieve compensation of pump function in the early phase of heart failure.http://journal.frontiersin.org/article/10.3389/fphys.2018.00037/fullejection fractionhypertrophycardiac compensationaortic bandingleft ventriclecomputational modeling |
| spellingShingle | Alexandre Lewalle Sander Land Eric Carruth Lawrence R. Frank Pablo Lamata Jeffrey H. Omens Jeffrey H. Omens Andrew D. McCulloch Andrew D. McCulloch Steven A. Niederer Nicolas P. Smith Nicolas P. Smith Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts Frontiers in Physiology ejection fraction hypertrophy cardiac compensation aortic banding left ventricle computational modeling |
| title | Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts |
| title_full | Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts |
| title_fullStr | Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts |
| title_full_unstemmed | Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts |
| title_short | Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts |
| title_sort | decreasing compensatory ability of concentric ventricular hypertrophy in aortic banded rat hearts |
| topic | ejection fraction hypertrophy cardiac compensation aortic banding left ventricle computational modeling |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2018.00037/full |
| work_keys_str_mv | AT alexandrelewalle decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT sanderland decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT ericcarruth decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT lawrencerfrank decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT pablolamata decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT jeffreyhomens decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT jeffreyhomens decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT andrewdmcculloch decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT andrewdmcculloch decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT stevenaniederer decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT nicolaspsmith decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts AT nicolaspsmith decreasingcompensatoryabilityofconcentricventricularhypertrophyinaorticbandedrathearts |