Circulation, Vol 86, 504-512, Copyright © 1992 by American Heart Association
JR Stratton, MD Cerqueira, RS Schwartz, WC Levy, RC Veith, SE Kahn and IB Abrass
BACKGROUND. Cardiac aging is characterized by a reduced heart rate response
to beta-agonist stimulation with isoproterenol, but whether the ejection
fraction and other cardiovascular responses are reduced in humans is
largely unknown. In addition, whether reduced beta-agonist responses can be
improved with exercise training has not been determined in humans. METHODS
AND RESULTS. Cardiovascular responses to graded isoproterenol infusions
(3.5, 7, 14, and 35 ng/kg/min for 14 minutes each) were assessed in 15
older (age, 60-82 years) and 17 young (age, 24-32 years) rigorously
screened healthy men. Thirteen older and 11 young subjects completed 6
months of endurance training and were retested. At baseline, the older
group had reduced responses to isoproterenol for heart rate (+65% older
versus +92% young, p less than 0.001), systolic blood pressure (+9% versus
+24%, p less than 0.001), diastolic blood pressure (-12% versus -24%, p
less than 0.05), ejection fraction (+12 versus +20 ejection fraction units,
p less than 0.001), and cardiac output (+70% versus +100%, p less than
0.001). The mean plasma isoproterenol concentrations achieved during the
infusions were marginally higher (p = 0.07) in the older group (128 +/- 58,
227 +/- 64, 354 +/- 114, and 700 +/- 125 pg/ml) than in the young (79 +/-
20, 178 +/- 49, 273 +/- 79, and 571 +/- 139 pg/ml). Intensive training
increased maximal oxygen consumption by 21% in the older group (28.9 +/-
4.6 to 35.1 +/- 3.8 ml/kg/min, p less than 0.001) and by 17% in the young
(44.5 +/- 5.1 to 52.1 +/- 6.3 ml/kg/min, p less than 0.001), but training
did not augment any of the cardiovascular responses to isoproterenol in
either group. The mean plasma isoproterenol concentrations at the four
infusion doses were unchanged after training in both groups. CONCLUSIONS.
We conclude that there is an age- associated decline in heart rate, blood
pressure, ejection fraction, and cardiac output responses to
beta-adrenergic stimulation with isoproterenol in healthy men. Altered
beta-adrenergic responses probably contribute to the reduced cardiac
responses to maximal exercise that also occur with aging. Furthermore,
intensive exercise training does not increase cardiac responses to
beta-adrenergic stimulation with isoproterenol in either young or older
men. The reduced beta-adrenergic response appears to be a primary
age-associated change that is not caused by disease or inactivity.
ARTICLES
Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men
Department of Medicine, Seattle VA Medical Center, WA 98108.
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