Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct
A growing proportion of heart failure (HF) patients present with impairments in both ventricles. Experimental pressure-overload (i.e., transverse aortic constriction, TAC) induces left ventricle (LV) hypertrophy and failure, as well as right ventricle (RV) dysfunction. However, little is known about...
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| Format: | Article |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2018.00472/full |
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| author | Mathew J. Platt Mathew J. Platt Jason S. Huber Jason S. Huber Nadya Romanova Nadya Romanova Keith R. Brunt Keith R. Brunt Jeremy A. Simpson Jeremy A. Simpson |
| author_facet | Mathew J. Platt Mathew J. Platt Jason S. Huber Jason S. Huber Nadya Romanova Nadya Romanova Keith R. Brunt Keith R. Brunt Jeremy A. Simpson Jeremy A. Simpson |
| author_sort | Mathew J. Platt |
| collection | DOAJ |
| description | A growing proportion of heart failure (HF) patients present with impairments in both ventricles. Experimental pressure-overload (i.e., transverse aortic constriction, TAC) induces left ventricle (LV) hypertrophy and failure, as well as right ventricle (RV) dysfunction. However, little is known about the coordinated progression of biventricular dysfunction that occurs in TAC. Here we investigated the time course of systolic and diastolic function in both the LV and RV concurrently to improve our understanding of the chronology of events in TAC. Hemodynamic, histological, and morphometric assessments were obtained from the LV and RV at 2, 4, 9, and 18 weeks post-surgery.Results: Systolic pressures peaked in both ventricles at 4 weeks, thereafter steadily declining in the LV, while remaining elevated in the RV. The LV and RV followed different structural and functional timelines, suggesting the patterns in one ventricle are independent from the opposing ventricle. RV hypertrophy/fibrosis and pulmonary arterial remodeling confirmed a progressive right-sided pathology. We further identified both compensation and decompensation in the LV with persistent concentric hypertrophy in both phases. Finally, diastolic impairments in both ventricles manifested as an intricate progression of multiple parameters that were not in agreement until overt systolic failure was evident.Conclusion: We establish pulmonary hypertension was secondary to LV dysfunction, confirming TAC is a model of type II pulmonary hypertension. This study also challenges some common assumptions in experimental HF (e.g., the relationship between fibrosis and filling pressure) while addressing a knowledge gap with respect to temporality of RV remodeling in pressure-overload. |
| first_indexed | 2024-04-11T23:56:13Z |
| format | Article |
| id | doaj.art-516eabf44e9e48a7a915ef2b33e7bf15 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-11T23:56:13Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-516eabf44e9e48a7a915ef2b33e7bf152022-12-22T03:56:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-05-01910.3389/fphys.2018.00472329784Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally DistinctMathew J. Platt0Mathew J. Platt1Jason S. Huber2Jason S. Huber3Nadya Romanova4Nadya Romanova5Keith R. Brunt6Keith R. Brunt7Jeremy A. Simpson8Jeremy A. Simpson9Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, CanadaIMPART Team Canada Investigator Network, Saint John, NB, CanadaDepartment of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, CanadaIMPART Team Canada Investigator Network, Saint John, NB, CanadaDepartment of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, CanadaIMPART Team Canada Investigator Network, Saint John, NB, CanadaIMPART Team Canada Investigator Network, Saint John, NB, CanadaDepartment of Pharmacology, Dalhousie Medicine New Brunswick, Saint John, NB, CanadaDepartment of Human Health & Nutritional Sciences, University of Guelph, Guelph, ON, CanadaIMPART Team Canada Investigator Network, Saint John, NB, CanadaA growing proportion of heart failure (HF) patients present with impairments in both ventricles. Experimental pressure-overload (i.e., transverse aortic constriction, TAC) induces left ventricle (LV) hypertrophy and failure, as well as right ventricle (RV) dysfunction. However, little is known about the coordinated progression of biventricular dysfunction that occurs in TAC. Here we investigated the time course of systolic and diastolic function in both the LV and RV concurrently to improve our understanding of the chronology of events in TAC. Hemodynamic, histological, and morphometric assessments were obtained from the LV and RV at 2, 4, 9, and 18 weeks post-surgery.Results: Systolic pressures peaked in both ventricles at 4 weeks, thereafter steadily declining in the LV, while remaining elevated in the RV. The LV and RV followed different structural and functional timelines, suggesting the patterns in one ventricle are independent from the opposing ventricle. RV hypertrophy/fibrosis and pulmonary arterial remodeling confirmed a progressive right-sided pathology. We further identified both compensation and decompensation in the LV with persistent concentric hypertrophy in both phases. Finally, diastolic impairments in both ventricles manifested as an intricate progression of multiple parameters that were not in agreement until overt systolic failure was evident.Conclusion: We establish pulmonary hypertension was secondary to LV dysfunction, confirming TAC is a model of type II pulmonary hypertension. This study also challenges some common assumptions in experimental HF (e.g., the relationship between fibrosis and filling pressure) while addressing a knowledge gap with respect to temporality of RV remodeling in pressure-overload.http://journal.frontiersin.org/article/10.3389/fphys.2018.00472/fulldiastolic dysfunctionpulmonary hypertensionleft heart diseaseconcentric remodelingmouse models |
| spellingShingle | Mathew J. Platt Mathew J. Platt Jason S. Huber Jason S. Huber Nadya Romanova Nadya Romanova Keith R. Brunt Keith R. Brunt Jeremy A. Simpson Jeremy A. Simpson Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct Frontiers in Physiology diastolic dysfunction pulmonary hypertension left heart disease concentric remodeling mouse models |
| title | Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct |
| title_full | Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct |
| title_fullStr | Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct |
| title_full_unstemmed | Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct |
| title_short | Pathophysiological Mapping of Experimental Heart Failure: Left and Right Ventricular Remodeling in Transverse Aortic Constriction Is Temporally, Kinetically and Structurally Distinct |
| title_sort | pathophysiological mapping of experimental heart failure left and right ventricular remodeling in transverse aortic constriction is temporally kinetically and structurally distinct |
| topic | diastolic dysfunction pulmonary hypertension left heart disease concentric remodeling mouse models |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2018.00472/full |
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