Differing autonomic response to dobutamine in the presence and absence of ischemia: implications for the autonomic contribution to positive inotropic intervention

Although it is well recognized that dobutamine is a powerful positive inotropic agent mediating increased myocardial contractility through direct β-adrenergic stimulation, the mechanism of its overall circulatory effects appears more complex than that which may be ascribed solely to this direct action on the myocardium. Previous investigations have implied that reflex alterations in autonomic balance may contribute significantly to the response to this agent, but direct evidence describing such a response has not been reported. The objective of this investigation was to assess changes in autonomic tone induced by dobutamine in the presence and absence of ischemia through the measurement of heart rate variability in patients undergoing dobutamine stress echocardiography. Of 25 consecutive patients undergoing dobutamine stress echocardiography, 16 were found to have unequivocal evidence for or against the presence of ischemia during dobutamine infusion. Heart rate data from these 16 patients were submitted for spectral analysis of heart rate variability and quantification of parasympathetically governed high-frequency heart rate variability and sympathetically influenced low-frequency heart rate variability. Of the 16 patients nine were not found to have evidence for ischemia (group 1), and seven were found to have echocardiographic findings consistent with dobutamine-induced ischemia (group 2). The two groups significantly differed (p = 0.04) in the change in parasympathetic tone associated with dobutamine with a significant (p = 0.04) increase in parasympathetic tone in group 1 and a numeric decrease in group 2. A significant (p = 0.04) decrease in sympathetic tone was noted in group 1 as reflected by low-frequency heart rate variability with a numeric increase in this measure in group 2. Patients in group 1 had significantly (p = 0.0007) increased ejection fraction and were found to have a significantly (p < 0.05) lower peak heart rate with dobutamine administration as compared with patients in group 2, who were not found to have any change in ejection fraction and who had a greater increase in peak heart rate over baseline. These results indicate that in the absence of myocardial ischemia dobutamine administration is associated with a significant increase in parasympathetic tone and reduction of sympathetic drive, which is not seen in patients in whom ischemia develops with dobutamine stimulation. The autonomic changes in the absence of ischemia may represent a reflex response to myocardial mechanoreceptor or arterial baroreceptor stimulation, which does not occur in the presence of ischemia. Therefore these data provide evidence that alterations in autonomic balance contribute significantly to the circulatory response to dobutamine and suggest that such reflex mechanisms contribute to the response to positive inotropic agents in general.