Ventricular structure and function in aged dogs with renal hypertension: A model of experimental diastolic heart failure

Vijaya K. Munagala, Chari Y T Hart, John C Jr. Burnett, Donna M. Meyer, Margaret May Redfield

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background - Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF. Methods and Results - Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (τ=53±6 ms) compared with OC (τ=35±3 ms; P<0.05) and YC (τ=33±6 ms; P<0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116±30%) compared with OC (69±8%; P<0.05) and YC (35±5%; P<0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs. Conclusions - Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.

Original languageEnglish (US)
Pages (from-to)1128-1135
Number of pages8
JournalCirculation
Volume111
Issue number9
DOIs
StatePublished - Mar 8 2005

Fingerprint

Diastolic Heart Failure
Renal Hypertension
Ventricular Function
Theoretical Models
Dogs
Vascular Stiffness
Fibrosis
Blood Pressure
Hypertension
Control Groups
Diastole
Left Ventricular Hypertrophy
Animal Models
Heart Failure
Kidney
Pressure

Keywords

  • Diastole
  • Heart failure
  • Hypertension
  • Kidney
  • Physiology

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ventricular structure and function in aged dogs with renal hypertension : A model of experimental diastolic heart failure. / Munagala, Vijaya K.; Hart, Chari Y T; Burnett, John C Jr.; Meyer, Donna M.; Redfield, Margaret May.

In: Circulation, Vol. 111, No. 9, 08.03.2005, p. 1128-1135.

Research output: Contribution to journalArticle

@article{76e2daddcb7c48868a1a8e4063fb207c,
title = "Ventricular structure and function in aged dogs with renal hypertension: A model of experimental diastolic heart failure",
abstract = "Background - Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF. Methods and Results - Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (τ=53±6 ms) compared with OC (τ=35±3 ms; P<0.05) and YC (τ=33±6 ms; P<0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116±30{\%}) compared with OC (69±8{\%}; P<0.05) and YC (35±5{\%}; P<0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs. Conclusions - Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.",
keywords = "Diastole, Heart failure, Hypertension, Kidney, Physiology",
author = "Munagala, {Vijaya K.} and Hart, {Chari Y T} and Burnett, {John C Jr.} and Meyer, {Donna M.} and Redfield, {Margaret May}",
year = "2005",
month = "3",
day = "8",
doi = "10.1161/01.CIR.0000157183.21404.63",
language = "English (US)",
volume = "111",
pages = "1128--1135",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Ventricular structure and function in aged dogs with renal hypertension

T2 - A model of experimental diastolic heart failure

AU - Munagala, Vijaya K.

AU - Hart, Chari Y T

AU - Burnett, John C Jr.

AU - Meyer, Donna M.

AU - Redfield, Margaret May

PY - 2005/3/8

Y1 - 2005/3/8

N2 - Background - Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF. Methods and Results - Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (τ=53±6 ms) compared with OC (τ=35±3 ms; P<0.05) and YC (τ=33±6 ms; P<0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116±30%) compared with OC (69±8%; P<0.05) and YC (35±5%; P<0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs. Conclusions - Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.

AB - Background - Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF. Methods and Results - Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (τ=53±6 ms) compared with OC (τ=35±3 ms; P<0.05) and YC (τ=33±6 ms; P<0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116±30%) compared with OC (69±8%; P<0.05) and YC (35±5%; P<0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs. Conclusions - Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.

KW - Diastole

KW - Heart failure

KW - Hypertension

KW - Kidney

KW - Physiology

UR - http://www.scopus.com/inward/record.url?scp=14944371449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14944371449&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000157183.21404.63

DO - 10.1161/01.CIR.0000157183.21404.63

M3 - Article

C2 - 15723971

AN - SCOPUS:14944371449

VL - 111

SP - 1128

EP - 1135

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 9

ER -