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 d irect beta-adrenergic stimulation, the mechanism of its overall circul atory effects appears more complex than that which may be ascribed sol ely to this direct action on the myocardium. Previous investigations h ave implied that reflex alterations in autonomic balance may contribut e significantly to the response to this agent, but direct evidence des cribing such a response has not been reported. The objective of this i nvestigation was to assess changes in autonomic tone induced by dobuta mine in the presence and absence of ischemia through the measurement o f heart rate variability in patients undergoing dobutamine stress echo cardiography. Of 25 consecutive patients undergoing dobutamine stress echocardiography, 16 were found to have unequivocal evidence for or ag ainst the presence of ischemia during dobutamine infusion. Heart rate data from these 16 patients were submitted for spectral analysis of he art rate variability and quantification of parasympathetically governe d high-frequency heart rate variability and sympathetically influenced low-frequency heart rate variability. Of the 16 patients nine were no t 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) i n the change in parasympathetic tone associated with dobutamine with a significant (p = 0.04) increase in parasympathetic tone in group 1 an d 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 he art rate variability with a numeric increase In this measure in group 2. Patients in group 1 had significantly (p = 0.0007) increased ejecti on fraction and were found to have a significantly (p < 0.05) lower pe ak heart rate with dobutamine administration as compared with patients in group 2, who were not found to have any change in ejection fractio n and who had a greater increase in peak heart rate over baseline. The se results indicate that in the absence of myocardial ischemia dobutam ine administration is associated with a significant increase in parasy mpathetic tone and reduction of sympathetic drive, which is not seen i n patients in whom ischemia develops with dobutamine stimulation. The autonomic changes in the absence of ischemia may represent a reflex re sponse to myocardial mechanoreceptor or arterial baroreceptor stimulat ion, which does not occur in the presence of ischemia. Therefore these data provide evidence that alterations in autonomic balance contribut e significantly to the circulatory response to dobutamine and suggest that such reflex mechanisms contribute to the response to positive ino tropic agents in general.