DOBUTAMINE ENHANCES CARDIODEPRESSANT EFFECTS OF RECEPTOR-MEDIATED CORONARY ENDOTHELIAL STIMULATION

Background In humans, intracoronary infusion of substance P reduces le ft ventricular end-systolic pressure and left ventricular peak systoli c pressure because of earlier onset of left ventricular relaxation ind uced by paracrine myocardial action of mediators released from the cor onary endothelium. The present study investigated in humans the effect s of beta-adrenergic stimulation, which also induces earlier left vent ricular relaxation, on the left ventricular myocardial contractile res ponse to intracoronary infusion of substance P. Methods and Results Da ta were obtained in 13 patients after cardiac transplantation and in 3 patients with dilated nonischemic cardiomyopathy. Microtip left ventr icular pressure recordings were obtained during a 5-minute intracorona ry infusion of substance P (20 pmol/min) under control conditions and then repeated during concurrent intravenous administration of dobutami ne. In the presence of dobutamine, intracoronary substance P caused a greater fall in left ventricular end-systolic pressure (transplantatio n control, -9+/-11 versus transplantation dobutamine, -20+/-18 mm Hg [ P<.05]; cardiomyopathy control, -4+/-1 versus cardiomyopathy dobutamin e, -10+/-3 mm Hg [P<.05]) and in left ventricular peak systolic pressu re (transplantation control, -14+/-10 versus transplantation dobutamin e, -30+/-22 mm Hg [P<.01]; cardiomyopathy control, -9+/-7 versus cardi omyopathy dobutamine, -15+/-6 mm Hg [P=.1]). Conclusions Dobutamine en hances the cardiodepressant effect on myocardial contractile performan ce of receptor-mediated coronary endothelial stimulation in transplant recipients and in patients with dilated nonischemic cardiomyopathy. T his enhancement could result from a potentiating interaction of the re laxation-hastening effect exerted by beta-adrenergic stimulation and b y mediators released from the coronary endothelium, such as nitric oxi de.