Circulation, Vol 90, 2333-2341, Copyright © 1994 by American Heart Association
JL Fleg, S Schulman, F O'Connor, LC Becker, G Gerstenblith, JF Clulow, DG Renlund and EG Lakatta
The cardiovascular response to beta-adrenergic stimulation is markedly
blunted with advancing age, and this blunting may underlie some of the
prominent age-associated changes in the hemodynamic profile during dynamic
exercise. To examine this hypothesis, we administered the nonselective
beta-adrenergic receptor blocker propranolol (0.15 mg/kg IV) to 25 healthy
normotensive men ages 28 to 72 years from the Baltimore Longitudinal Study
of Aging (BLSA) immediately before maximal upright cycle ergometry with
99mTc gated cardiac blood pool scintigraphy. Their hemodynamic responses to
exercise were compared with those of 70 age-matched healthy unmedicated
male BLSA control subjects. The maximal cycle work rate achieved was
similar in propranolol-treated men (158 +/- 32 W) and control subjects (148
+/- 32 W) and declined similarly with age in both groups. Hemodynamics at
seated rest were not age-related in either group; however, propranolol-
treated men had lower heart rates (HR), systolic blood pressure (SBP),
ejection fraction, and cardiac index than control subjects but higher
end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) by
covariance analysis. At maximal effort, several striking age-drug
interactions were evident: Propranolol caused a greater reduction in HR and
greater increases in EDVI and stroke volume index (SVI) in younger than in
older men. Hence, at maximal work rate, HR declined less with age in the
propranolol group (0.46 versus 1.09 beats per minute per year, P < .05
by covariance analysis); EDVI and SVI decreased with age (0.27 and 0.48
mL/m2 per year, respectively) after propranolol compared with increases of
0.47 and 0.16 mL/m2 per year in control subjects, respectively, each P <
or = .05 by covariance analysis. The left ventricular contractility index,
SBP/ESVI, at exhaustion was reduced by propranolol to a greater extent in
younger than older men. Thus, acute beta-adrenergic blockade reverses the
age-associated ventricular dilation at end diastole and end systole
observed during upright cycle exercise and blunts the decline in maximal HR
and myocardial contractility. These data suggest that the age-associated
declines in maximal HR and left ventricular contractility during vigorous
exercise are manifestations of reduced beta-adrenergic responsivity with
advancing age which is partially offset by exercise-induced ventricular
dilation.
ARTICLES
Effects of acute beta-adrenergic receptor blockade on age-associated changes in cardiovascular performance during dynamic exercise
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Md.
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