Pathophysiological mapping of experimental heart failure: Left and right ventricular remodeling in transverse aortic constriction is temporally, kinetically and structurally distinct

Mathew J. Platt, Jason S. Huber, Nadya Romanova, Keith R. Brunt, Jeremy A. Simpson

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28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number472
JournalFrontiers in Physiology
Volume9
Issue numberMAY
DOIs
Publication statusPublished - May 15 2018

Bibliographical note

Funding Information:
This work was supported by grants from National Science Research Engineering Council (KB and JS), a Canadian Institutes of Health Research grant (MOP 111159 to JS), and a Heart and Stroke Foundation of Canada grant (JS and KB). JS is also a New Investigator of the Heart and Stroke Foundation of Canada. We further acknowledge the philanthropic support for cardiovascular research from Betty and Jack Southen, of London ON and from Matthew O'Hara, of Guelph ON to the laboratory of JS. We sincerely thank Ian Smith for his generation of Figure 9.

Publisher Copyright:
© 2018 Platt, Huber, Romanova, Brunt and Simpson.

ASJC Scopus Subject Areas

  • Physiology
  • Physiology (medical)

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