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(Hypertension. 2006;47:901.)
© 2006 American Heart Association, Inc.

Original Articles

Development of Heart Failure in Chronic Hypertensive Dahl Rats

Focus on Heart Failure With Preserved Ejection Fraction

Stefan Klotz; Ilan Hay; Geping Zhang; Mathew Maurer; Jie Wang; Daniel Burkhoff

From the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.

Correspondence to Daniel Burkhoff, Jack H Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, 8 Corporate Dr, Orangeburg, NY 10962. E-mail dburkhoff{at}crf.org

The impact of hypertension on left ventricular (LV) structure, pump function, and heart failure in Dahl salt-sensitive rats is poorly characterized but hypothesized to yield insights into the pathophysiology of heart failure with normal or preserved ejection fraction. Eighty Dahl salt-sensitive rats were fed either a high-salt (HS) or low-salt (LS, controls) diet starting at age 7 weeks. Ventricular properties were measured by echocardiography, hemodynamics and end-systolic and end-diastolic pressure-volume relationships (ESPVR and EDPVR, respectively). Compared with LS controls, HS rats developed severe hypertension and LV hypertrophy. At week 12, HS rats developed passive diastolic dysfunction (leftward/upward shifted EDPVR, increased chamber stiffness) with reductions in end-diastolic volume. However, the ESPVR also shifted upward (enhanced end-systolic function) so that overall pump function was enhanced compared with LS, and there was no change in end-diastolic pressure (EDP). At 16 and 20 weeks, HS hearts enlarged so that end-diastolic volumes and EDPVRs became similar to the respective age-matched LS controls. Concomitantly, the ESPVRs and overall pump function curves also moved toward controls, and ejection fraction declined. Despite normal or enhanced overall pump function at these times, EDP and wet lung weight increased, indicative of development of heart failure. In the Dahl salt-sensitive rat, which pathophysiologically retains salt and water, the development of heart failure (increased EDP and wet lung weight) is dissociated from changes in passive diastolic and active systolic properties. These observations suggest that a volume overload sate plays an important pathophysiological role in development of heart failure despite preserved overall ventricular pump function in this model of chronic hypertension.

Key Words: remodeling • heart failure • diastole • hypertrophy • renal disease

Related Article:

Understanding Diastolic Heart Failure With Preserved Ejection Fraction: Choosing the Right Model

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