Coronary Vessel Supersensitivity to Noradrenaline in the Presence of Chronic Sympathetic Denervation

It is well known that there is usually super-sensitivity to the normal neurotransmitter in chronically denervated organs. The present consensus of opinion is that there is no super-sensitivity of response of myocardial arteriolar resistance vessels to nor-adrenaline after chronic sympathetic denervation; this opinion was tested. We re-analysed the data in the literature on innervated myocardium, plus the effect of chronic sympathetic myocardial denervation induced by surgery plus phenol application. We found that the opinion is based on studies of isolated epicardial arteries. Studies of resistance vessels mostly ignore an important confounding factor, in that myocardial blood flow (MBF) within myocardium is heterogeneous under all circumstances. This heterogeneity is partly related to similar heterogeneity in myocardial oxygen consumption (MVO2), and partly to heterogeneity in local noradrenaline, as assessed by 11C-hydroxyephidrine positron emission tomography. The local volume of distribution of 11C-hydroxyephedrine in innervated myocardium was inversely correlated to local MBF, at the same perfusion pressure, i.e., increasing vasoconstriction with increasing tissue noradrenaline. In chronically denervated myocardium, local MBF was lower for any given amount of noradrenaline, showing the existence of supersensitivity of the resistance vessels. This factor may have a deletereous effect in diabetic patients with cardiac autonomic neuropathy.