Effects of normal aging on left ventricular lusitropic, inotropic, and chronotropic responses to dobutamine.
OBJECTIVE
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 beta-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 mug/kg/min). The LV function was evaluated by two-dimensional and Doppler echocardiography. Myocardial relaxation was evaluated from cardiovascular magnetic resonance (CMR)-based rho, a preload-independent surrogate for tau . 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 rho 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.
Hees
Paul S
PS
Department of Medicine and Division of Cardiology, School of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. phees@welch.jhu.edu
Fleg
Jerome L
JL
Mirza
Zulfiqar A
ZA
Ahmed
Sujood
S
Siu
Cynthia O
CO
Shapiro
Edward P
EP
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D012016:Reference Values; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D004280:Dobutamine