BackgroundThe role of cholinergic pathways in modulating left ventricular contractile function in humans is not known. This study evaluated the effect of a cholinergic agonist (acetylcholine) and antagonist (atropine) on basal and β-adrenergically stimulated left ventricular contractile function in normal subjects and subjects with denervated hearts after cardiac transplantation.Methods and ResultsSix subjects with normal left ventricular function and seven subjects who were 1 to 3 years after cardiac transplantation were studied. Acetylcholine, atropine, and the β-adrenergic agonist dobutamine were infused via the left main coronary artery, and changes in left ventricular contractile function were assessed by measurement of peak +dP/dt. Intracoronary dobutamine increased +dP/dt by 70±15% and 66±20% in the normal subjects and transplant recipients, respectively. Intracoronary acetylcholine and atropine alone each had no effect on left ventricular +dP/dt in either normal subjects or transplant recipients. The concurrent infusion of acetylcholine with dobutamine reduced the response to dobutamine by 66±10% and 79±9% in normal subjects and transplant recipients, respectively. The concurrent infusion of atropine with dobutamine potentiated the response to dobutamine by 25±7% in normal subjects but had no effect in transplant recipients.ConclusionsStimulation and inhibition of cholinergic receptors in the human heart can modulate the positive inotropic response to β-adrenergic stimulation.