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Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

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Abstract
Myocardial stiffness and upward-shifted end-diastolic pressure-volume (P-V) relationship (EDPVR) are the key to high filling pressures in heart failure with preserved ejection fraction (HFpEF). Nevertheless, many patients may remain asymptomatic unless hemodynamic stress is imposed on the myocardium. Whether delayed relaxation induced by pressure challenge may contribute to high end-diastolic pressure (EDP) remains unsettled. Our aim was to assess the effect of suddenly imposed isovolumic afterload on relaxation and EDP, exploiting a highly controlled P-V experimental evaluation setup in the ZSF1 obese rat (ZSF1 Ob) model of HFpEF. Twenty-week-old ZSF1 Ob (n = 12), healthy Wistar-Kyoto rats (WKY, n = 11), and hypertensive ZSF1 lean control rats (ZSF1 Ln, n = 10) underwent open-thorax left ventricular (LV) P-V hemodynamic evaluation under anesthesia with sevoflurane. EDPVR was obtained by inferior vena cava occlusions to assess LV ED chamber stiffness constant β, and single-beat isovolumic afterload acquisitions were obtained by swift occlusions of the ascending aorta. ZSF1 Ob showed increased ED stiffness, delayed relaxation, as assessed by time constant of isovolumic relaxation (τ), and elevated EDP with normal ejection fraction. Isovolumic afterload increased EDP without concomitant changes in ED volume or heart rate. In isovolumic beats, relaxation was delayed to the extent that time for complete relaxation as predicted by 3.5 × monoexponentially derived τ (τexp) exceeded effective filling time. EDP elevation correlated with reduced time available to relax, which was the only independent predictor of EDP rise in multiple linear regression. Our results suggest that delayed relaxation during pressure challenge is an important contributor to lung congestion and effort intolerance in HFpEF.
Keywords
diastolic function, heart failure with preserved ejection fraction, time-varying load, ventricular-arterial coupling, afterload, HFpEF, relaxation, ACTIVE RELAXATION, MYOCARDIAL RELAXATION, LEFT-VENTRICLE, EXERCISE, CONTRACTION, VOLUME RELATION, DIAGNOSIS, RESERVE, ECHOCARDIOGRAPHY, PATHOPHYSIOLOGY

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MLA
Leite, Sara et al. “Afterload-induced Diastolic Dysfunction Contributes to High Filling Pressures in Experimental Heart Failure with Preserved Ejection Fraction.” AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 309.10 (2015): H1648–H1654. Print.
APA
Leite, S., Rodrigues, S., Tavares-Silva, M., Oliveira-Pinto, J., Alaa, M., Abdellatif, M., Fontoura, D., et al. (2015). Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 309(10), H1648–H1654.
Chicago author-date
Leite, Sara, Sara Rodrigues, Marta Tavares-Silva, José Oliveira-Pinto, Mohamed Alaa, Mahmoud Abdellatif, Dulce Fontoura, et al. 2015. “Afterload-induced Diastolic Dysfunction Contributes to High Filling Pressures in Experimental Heart Failure with Preserved Ejection Fraction.” American Journal of Physiology-heart and Circulatory Physiology 309 (10): H1648–H1654.
Chicago author-date (all authors)
Leite, Sara, Sara Rodrigues, Marta Tavares-Silva, José Oliveira-Pinto, Mohamed Alaa, Mahmoud Abdellatif, Dulce Fontoura, Inês Falcão-Pires, Thierry Gillebert, Adelino F Leite-Moreira, and André P Lourenço. 2015. “Afterload-induced Diastolic Dysfunction Contributes to High Filling Pressures in Experimental Heart Failure with Preserved Ejection Fraction.” American Journal of Physiology-heart and Circulatory Physiology 309 (10): H1648–H1654.
Vancouver
1.
Leite S, Rodrigues S, Tavares-Silva M, Oliveira-Pinto J, Alaa M, Abdellatif M, et al. Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. 2015;309(10):H1648–H1654.
IEEE
[1]
S. Leite et al., “Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction,” AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, vol. 309, no. 10, pp. H1648–H1654, 2015.
@article{6998035,
  abstract     = {{Myocardial stiffness and upward-shifted end-diastolic pressure-volume (P-V) relationship (EDPVR) are the key to high filling pressures in heart failure with preserved ejection fraction (HFpEF). Nevertheless, many patients may remain asymptomatic unless hemodynamic stress is imposed on the myocardium. Whether delayed relaxation induced by pressure challenge may contribute to high end-diastolic pressure (EDP) remains unsettled. Our aim was to assess the effect of suddenly imposed isovolumic afterload on relaxation and EDP, exploiting a highly controlled P-V experimental evaluation setup in the ZSF1 obese rat (ZSF1 Ob) model of HFpEF. Twenty-week-old ZSF1 Ob (n = 12), healthy Wistar-Kyoto rats (WKY, n = 11), and hypertensive ZSF1 lean control rats (ZSF1 Ln, n = 10) underwent open-thorax left ventricular (LV) P-V hemodynamic evaluation under anesthesia with sevoflurane. EDPVR was obtained by inferior vena cava occlusions to assess LV ED chamber stiffness constant β, and single-beat isovolumic afterload acquisitions were obtained by swift occlusions of the ascending aorta. ZSF1 Ob showed increased ED stiffness, delayed relaxation, as assessed by time constant of isovolumic relaxation (τ), and elevated EDP with normal ejection fraction. Isovolumic afterload increased EDP without concomitant changes in ED volume or heart rate. In isovolumic beats, relaxation was delayed to the extent that time for complete relaxation as predicted by 3.5 × monoexponentially derived τ (τexp) exceeded effective filling time. EDP elevation correlated with reduced time available to relax, which was the only independent predictor of EDP rise in multiple linear regression. Our results suggest that delayed relaxation during pressure challenge is an important contributor to lung congestion and effort intolerance in HFpEF.}},
  author       = {{Leite, Sara and Rodrigues, Sara and Tavares-Silva, Marta and Oliveira-Pinto, José and Alaa, Mohamed and Abdellatif, Mahmoud and Fontoura, Dulce and Falcão-Pires, Inês and Gillebert, Thierry and Leite-Moreira, Adelino F and Lourenço, André P}},
  issn         = {{0363-6135}},
  journal      = {{AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY}},
  keywords     = {{diastolic function,heart failure with preserved ejection fraction,time-varying load,ventricular-arterial coupling,afterload,HFpEF,relaxation,ACTIVE RELAXATION,MYOCARDIAL RELAXATION,LEFT-VENTRICLE,EXERCISE,CONTRACTION,VOLUME RELATION,DIAGNOSIS,RESERVE,ECHOCARDIOGRAPHY,PATHOPHYSIOLOGY}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{H1648--H1654}},
  title        = {{Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction}},
  url          = {{http://dx.doi.org/10.1152/ajpheart.00397.2015}},
  volume       = {{309}},
  year         = {{2015}},
}

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