Myocardial Presynaptic and Postsynaptic Autonomic Dysfunction in Hypertrophic Cardiomyopathy

Abstract

Although hypertrophic cardiomyopathy (HCM) is genetically determined, several other factors, including autonomic dysfunction, may play a role in the phenotypic expression. A recent study using positron emission tomography with [11C]CGP 12177 ([11C]CGP) demonstrated that beta-adrenoceptor (betaAR) density is reduced in HCM and is correlated with disease progression. This present study tested the hypothesis that this downregulation is associated with reduced catecholamine reuptake (uptake 1) by myocardial sympathetic nerve terminals leading to increased local norepinephrine concentration. Myocardial presynaptic catecholamine reuptake was assessed by measuring the volume of distribution (Vd) of the catecholamine analogue [11C]hydroxyephedrine ([11C]HED) in 9 unrelated HCM patients aged 45+/-15 years. The maximum number of binding sites (Bmax) for myocardial betaAR density was measured in 13 unrelated HCM patients aged 40+/-12 years using the nonselective beta blocker [11C]CGP. Six patients were studied with both [11C]HED and [11C]CGP. Comparison was made with two groups of healthy control subjects for each ligand ([11C]HED, n=10, aged 35+/-8 years; [11C]CGP, n=19, aged 44+/-16 years). Myocardial Vd of [11C]HED (33.4+/-4.3 mL/g tissue) and betaAR density (7.3+/-2.6 pmol/g tissue) were significantly reduced in HCM patients compared with control subjects (71.0+/-18.8 mL/g tissue, P<.001, and 10.2+/-2.9 pmol/g tissue, P=.008, respectively). These results are consistent with our hypothesis that myocardial betaAR downregulation in HCM is associated with an impaired uptake-1 mechanism and hence increased local catecholamine levels.

Avaliação da função autonômica na cardiomiopatia hipertrófica

“…Brush and collaborators (1989) demonstrated that neuronal uptake of norepinephrine was reduced in HCM patients, thus emphasizing the assumption that sympathetic nervous system disorders might be related to phenomena found in that condition, particularly sudden death 4 . Schafers and collaborators also verifi ed decrease in beta receptors density in that condition, in addition to reduction in norepinephrine neuronal uptake 5 .…”

“…When detecting a reduction of neuronal uptake in nervous terminations, those studies suggest that the disease would be characterized by the increase in sympathetic activity due to the longer presence of norepinephrine in the synaptic gap [3][4][5] .…”

Hipertrofik kardiyomiyopatili hastaların risk sınıflandırmasında görüntüleme yöntemlerinin yeri

“…Bu yöntemlerin etkinliği ile HKM'nin patofizyolojisi, kalp yetersizliği ve AKÖ açısından riskli grupların tespiti mümkün olabilecektir (59)(60)(61)(62)(63).…”

Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy

“…9 Studies evaluating the accuracy and reproducibility of 11 C-CGP-12177 and PET for the quantification of ␤-adrenergic receptor density showed excellent results. 16,17 After initial rectilinear, transmission, and blood volume ([ 15 O]CO) scanning, measurement of myocardial ␤-adrenergic receptor density was performed according to a modification of the double-injection method previously reported in detail. 18,19 During a dynamic emission scan, a first dose of 11 C-CGP-12177 with high specific activity (170Ϯ10 MBq, 4.2Ϯ0.4 g cold CGP-12177) was infused intravenously over a 2-minute period.…”