Dobutamine enhances cardiodepressant effects of receptor-mediated coronary endothelial stimulation.

BACKGROUND

In humans, intracoronary infusion of substance P reduces left ventricular end-systolic pressure and left ventricular peak systolic pressure because of earlier onset of left ventricular relaxation induced by paracrine myocardial action of mediators released from the coronary endothelium. The present study investigated in humans the effects of beta-adrenergic stimulation, which also induces earlier left ventricular relaxation, on the left ventricular myocardial contractile response to intracoronary infusion of substance P.

METHODS AND RESULTS

Data were obtained in 13 patients after cardiac transplantation and in 3 patients with dilated nonischemic cardiomyopathy. Microtip left ventricular pressure recordings were obtained during a 5-minute intracoronary infusion of substance P (20 pmol/min) under control conditions and then repeated during concurrent intravenous administration of dobutamine. In the presence of dobutamine, intracoronary substance P caused a greater fall in left ventricular end-systolic pressure (transplantation control, -9 +/- 11 versus transplantation dobutamine, -20 +/- 18 mm Hg [P < .05]; cardiomyopathy control, -4 +/- 1 versus cardiomyopathy dobutamine, -10 +/- 3 mm Hg [P < .05]) and in left ventricular peak systolic pressure (transplantation control, -14 +/- 10 versus transplantation dobutamine, -30 +/- 22 mm Hg [P < .01]; cardiomyopathy control, -9 +/- 7 versus cardiomyopathy dobutamine, -15 +/- 6 mm Hg [P = .1]).

CONCLUSIONS

Dobutamine enhances the cardiodepressant effect on myocardial contractile performance of receptor-mediated coronary endothelial stimulation in transplant recipients and in patients with dilated nonischemic cardiomyopathy. This enhancement could result from a potentiating interaction of the relaxation-hastening effect exerted by beta-adrenergic stimulation and by mediators released from the coronary endothelium, such as nitric oxide.