Background - The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by 123I-MIBG-single-photon emission computed tomography. Methods and Results - This study investigated neuronal reuptake of norepinephrine (uptake-1) and β-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V(d)) of [11C]hydroxyephedrine (11C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B(max)) of [11C]CGP-12177 (11C- CGP-12177) to assess postsynaptic β-adrenergic receptor density, and [15O]H2O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic β- adrenergic receptor density compared with that in control subjects (B(max) of 11C-CGP-12177: 5.9±1.3 vs 10.2±2.9 pmol/g tissue, P11C-HED: 59.1±25.2 vs 71.0±18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects. Conclusions - The findings demonstrate a significant reduction of myocardial β-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine uptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.
|Number of pages||7|
|Publication status||Published - Apr 4 2000|
- Nervous system, autonomic
- Receptors, adrenergic, beta
- Ventricular tachycardia
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine