Effects of acute beta-adrenergic receptor blockade on age-associated changes in cardiovascular performance during dynamic exercise.
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.
Fleg, JL; Schulman, S; O'Connor, F; Becker, LC; Gerstenblith, G; Clulow, JF; Renlund, DG; Lakatta, EG
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