Heart rate responsiveness after sustained chronotropic stimulation with a beta 1-adrenergic receptor agonist

Six normal male human subjects underwent two 72 hr infusions of saline (control) and butopamine, a beta-adrenergic agonist with strong positive chronotropic properties, in order to determine the chronotropic responsiveness of the human heart after sustained chronotropic stimulation. Chronotropic responsiveness was assessed by heart rate responses to intravenous isoproterenol and bicycle ergometry before and serially over 50 hr after discontinuation of the infusions. Chronotropic responsiveness to isoproterenol and exercise was reduced significantly in the butopamine group compared to control; this blunted chronotropic effect persisted beyond 48 hr. Positive inotropic responsiveness, assessed by echocardiography and systolic time intervals, was reduced modestly for the butopamine-treated group up to 24 hr after infusion. Although the precise mechanisms are not fully elucidated, continuous chronotropic stimulation of the human heart with the beta 1 agonist, butopamine, elicits a significant reduction in the heart rate response to isoproterenol and exercise challenges. In addition, the degree and time course of suppression of the chronotropic vs. inotropic responsiveness are disparate.