MYOCARDIAL PRESYNAPTIC AND POSTSYNAPTIC AUTONOMIC DYSFUNCTION IN HYPERTONIC CARDIOMYOPATHY

Although hypertrophic cardiomyopathy (HCM) is genetically determined, several other factors, including autonomic dysfunction, may play a rol e in the phenotypic expression. A recent study using positron emission tomography with [C-11]CGP12177([C-11]CGP) demonstrated that beta-adre noceptor (beta AR) density is reduced in HCM and is correlated with di sease progression, This present study tested the hypothesis that this downregulation is associated with reduced catecholamine reuptake (upta ke 1) by myocardial sympathetic nerve terminals leading to increased l ocal norepinephrine concentration. Myocardial presynaptic catecholamin e reuptake was assessed by measuring the volume of distribution (V-d) of the catecholamine analogue [C-11]hydroxyephedrine ([C-11]HED) in 9 unrelated HCM patients aged 45 +/- 15 years. The maximum number of bin ding sites (B-max) for myocardial beta AR density was measured in 13 u nrelated HCM patients aged 40 +/- 12 years using the nonselective beta blocker [C-11]CGP. Six patients were studied with both [C-11]HED and [C-11]CGP. Comparison was made with two groups of healthy control subj ects for each ligand ([C-11]HED, n = 10, aged 35 +/- 8 years; [C-11]CG P, n = 19, aged 44 +/- 16 years). Myocardial V-d of [C-11]HED (33.4 +/ - 4.3 mL/g tissue) and beta AR density (7.3 +/- 2.6 pmol/g tissue) wer e 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 hypoth esis that myocardial beta AR downregulation in HCM is associated with an impaired uptake-1 mechanism and hence increased local catecholamine levels.