Cardiac chronotropic responsiveness to beta-adrenoceptor stimulation is not reduced in the elderly

Abstract

This study evaluated cardiac beta-adrenoceptor responsiveness in the elderly. The hypothesis of reduced cardiac beta-adrenoceptor responsiveness in the elderly is based on a smaller increase in heart rate after administration of isoproterenol, a nonselective beta 1- and beta 2-adrenoceptor agonist. By means of dobutamine-stress-echocardiography we were able to retest the hypothesis more accurately because dobutamine is a relatively selective beta 1-adrenoceptor agonist with weak beta 2- and alpha-adrenoceptor stimulant activity that prevents baroreflex-mediated changes in heart rate. After administration of stepwise incremental infusions of dobutamine, we measured heart rate and blood pressure responses in 360 patients who had no beta-adrenergic blocking agent therapy and no side effects during the stress test. For each patient we calculated the dose of dobutamine required to increase heart rate by 50% of the maximal heart rate during the highest dose of dobutamine. No relation was found between age and sensitivity to dobutamine (n = 293). Power analysis revealed that this negative finding was not the result of inadequate sample size. In contrast to the prevailing hypothesis, an increased heart rate response to dobutamine was found even in a subgroup of "healthy" elderly subjects (i.e., those without concomitant disease or acute myocardial ischemia, n = 67) that was not related to changes in blood pressure during stress. However, in subjects with acute ischemia (n = 109), smokers (n = 151) or patients with a history of a previous myocardial infarction (n = 148), dobutamine sensitivity was reduced in the elderly despite a diminished change in systolic blood pressure with advanced age during dobutamine infusion. This phenomenon could be explained by a decrease in efferent cardiac baroreflex sensitivity, as has been observed during acute myocardial ischemia. There were no age-related differences in plasma concentrations of dobutamine. No evidence for reduced beta-adrenoceptor responsiveness to dobutamine was found in "healthy" elderly subjects.