Functional effects of cardiac sympathetic denervation in neurogenic orthostatic hypotension

Abstract

Background-Diseases characterized by neurogenic orthostatic hypotension (NOH), such as Parkinson disease (PD) and pure autonomic failure (PAF), are associated with cardiac sympathetic denervation, as reflected by low myocardial concentrations of 6-[ 18 F]fluorodopamine-derived radioactivity. We studied the impact of such denervation on cardiac chronotropic and inotropic function.

Cardiovascular autonomic dysfunction in MSA and Parkinson's disease: Similarities and differences

“…Patients with PD have low cardiac noradrenaline spillover reflecting reduced cardiac sympathetic innervation [42,45] with loss of tyrosine hydroxylase in the epicardium [17]. Cardiac denervation is also associated with a decreased ability to release endogenous norepinephrine from sympathetic nerves and a supersensitivity of cardiac beta-adrenoreceptors [49]. These findings are consistent with a relative sparing of brain autonomic centres and intracerebral sympathetic pathways in PD, and their involvement in MSA [50,51].…”

Cardiocirculatory manifestations in Parkinson's disease patients without orthostatic hypotension

“…The main mechanism could be related with adrenergic denervation supersensitivity, as patients with cardiac denervation show exaggerated response to infused catecholamine in experimental studies. 27 Other possible mechanism would be the greater decrease in norepinephrine clearance seen in PD patients. 28 We previously published evidences supporting a selective vulnerability in the heart on the basis of normal catecholamine levels and the absence of orthostatic hypotension in symptomatic and asymptomatic carriers of genetic mutations of alpha-synuclein (SNCA) gene.…”

Occurrence of Takotsubo syndrome in a patient with Parkinson's disease after entacapone add-on

“…Furthermore, our patient had a reduced cardiac MIBG uptake before shifting to entacapone therapy, in keeping with the well-known abnormal cardiac noradrenergic denervation in PD patients, together with a myocardial perfusion that is usually normal. This suggests a functional alteration in the presynaptic cardiac sympathetic neurotransmission, which was reported to be associated with a supersensitivity of cardiac beta-adrenoceptors, as indicated by an increased tachycardic response to isoproterenol infusion in PD patients [3]. Of note, a functional alteration in presynaptic sympathetic neurotransmission has been previously described in patients with TTS [4], suggesting some analogy with myocardial dysautonomia in PD patients.…”

“…Iatrogenic forms have been previously reported following sympathomimetic drug administration for therapeutic and diagnostic purposes [3]. Since c-COMT activity inactivates catecholamines in myocardial tissue, a reduction in COMT activity could lead to an increased bioavailability of catecholamines [1].…”