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

• Published in: Journal of the American College of Cardiology Vol. 47; no. 7; pp. 1440 - 1447
• Main Authors: Hees, Paul S., Fleg, Jerome L., Mirza, Zulfiqar A., Ahmed, Sujood, Siu, Cynthia O., Shapiro, Edward P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 04.04.2006; Elsevier Science; Elsevier Limited
• Subjects: Adult; Age; Aged; Aging - physiology; Biological and medical sciences; Blood pressure; Cardiology; Cardiology. Vascular system; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Cardiovascular disease; Dobutamine - administration & dosage; Dobutamine - pharmacology; Dose-Response Relationship, Drug; Echocardiography; Family medical history; Female; Heart; Heart Rate - drug effects; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Myocardial Contraction - drug effects; Personal computers; Reference Values; Software; Studies; Ventricular Function, Left - drug effects; SBP; ρ; CMR; PFi; LV; τ; Response; Ageing; Dobutamine; Circulatory system; Cardiology; Normal; Phlebology; Left ventricle
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.11.052

Effects of Normal Aging on Left Ventricular Lusitropic, Inotropic, and Chronotropic Responses to Dobutamine Paul S. Hees, Jerome L. Fleg, Zulfiqar A. Mirza, Sujood Ahmed, Cynthia O. Siu, Edward P. Shapiro Tagged cine cardiovascular magnetic resonance and echocardiographic imaging were performed at rest and during graded infusions of dobutamine in carefully screened volunteers to assess the effect of age on left ventricular reserve. The young patients showed greater inotropic but not chronotropic reserve; they also had greater lusitropic but not relaxation reserve than older adults. The purpose of this study was to characterize how aging impacts the left ventricular (LV) functional reserve. Early diastolic LV filling slows markedly with advancing age, but the effects of β-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. 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 ρ, a preload-independent surrogate for τ . Effective LV pump-function index (PFi), defined as systolic blood pressure/end-systolic LV diameter, was measured. 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 ρ 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). 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.