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CLINICAL RESEARCH: CARDIOVASCULAR EFFECT OF AGING

Effects of Normal Aging on Left Ventricular Lusitropic, Inotropic, and Chronotropic Responses to Dobutamine

Paul S. Hees, PhD^_*,_*, Jerome L. Fleg, MD, Zulfiqar A. Mirza, MD, Sujood Ahmed, MD, Cynthia O. Siu, PhD, MBA^|| and Edward P. Shapiro, MD^_*

^_* Department of Medicine and Division of Cardiology, School of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
Department of Medicine and Division of Cardiology, School of Medicine, Wright State University, Dayton, Ohio
Department of Medicine and Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama
^|| Data Power Inc, Ringoes, New Jersey.

Manuscript received February 8, 2005; revised manuscript received November 1, 2005, accepted November 7, 2005.

^_* Reprint requests and correspondence: Dr. Paul S. Hees, Cardiology Division, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, Maryland 21224. (Email: phees{at}welch.jhu.edu).

OBJECTIVES: The purpose of this study was to characterize how aging impacts the left ventricular (LV) functional reserve.

BACKGROUND: Early diastolic LV filling slows markedly with advancing age, but the effects of ß-adrenergic stimulation on filling, and its major determinant, relaxation, have not been investigated in an aging population. Although the responses of contractility and heart rate to catecholamines reportedly diminish with age, the effect of age on the responses to steady-state dobutamine infusions is unclear.

METHODS: Groups of younger (40 ± 10 years, n = 26) and older (68 ± 11 years, n = 24) normal adult patients were studied at baseline and at three progressive dobutamine infusion dosages (5, 10, and 20 µg/kg/min). The LV function was evaluated by two-dimensional and Doppler echocardiography. Myocardial relaxation was evaluated from cardiovascular magnetic resonance (CMR)-based , a preload-independent surrogate for . Effective LV pump-function index (PFi), defined as systolic blood pressure/end-systolic LV diameter, was measured.

RESULTS: Both groups showed expected dose-dependent increases in heart rate and LV systolic function, diastolic function, and relaxation. Early LV filling reserve was much greater in younger than older patients (E-wave increase from baseline to highest dose, 24.0 vs. 9.5 cm/s, p < 0.004), although the dose responses of were indistinguishable (0.18% vs. 0.19%/ms, p = 0.22). Whereas dobutamine caused a significantly greater increase of PFi in younger than older patients (30.1 vs. 15.6 mm Hg/cm, p < 0.0001), there was no difference in heart rate augmentation (37 vs. 38 beats/min, p = 0.94).

CONCLUSIONS: Aging is accompanied by a blunted inotropic but preserved chronotropic response to steady-state dobutamine infusion. Although LV filling reserve declines with age, relaxation reserve does not.

Abbreviations and Acronyms   CMR = cardiovascular magnetic resonance   LV = left ventricular   PFi = pump function index   SBP = systolic blood pressure    = slope of diastolic LV myocardial recoil; CMR-based recoil rate    = time constant of diastolic LV pressure decrease; measure of relaxation

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