Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy

J. E. Brush, G. Eisenhofer, M. Garty, R. Stull, B. J. Maron, R. O. Cannon, J. A. Panza, J. E. Epstein, D. S. Goldstein

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the uptake and release of norepinephrine in the cardiac circulation and other regional vascular beds in 11 patients with hypertrophic cardiomyopathy (HCM) and in 10 control subjects during simultaneous infusion of tracer-labeled norepinephrine and isoproterenol. Cardiac neuronal uptake norepinephrine was assessed by comparing regional removal of tracer-labeled norepinephrine with that of tracer-labeled isoproterenol (which is not a substrate for neuronal uptake) and by the relation between production of dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, and regional spillover of norepinephrine. Cardiac extraction of norepinephrine averaged 59 ± 17% in the patients with HCM, significantly less than in the control subjects (79 ± 13%, p < 0.05), whereas cardiac extraction of isoproterenol was similar in the two groups (13 ± 23% versus 13 ± 14%), indicating that neuronal uptake of norepinephrine was decreased in the patients with HCM. The cardiac arteriovenous difference in norepinephrine was significantly larger in the patients with HCM than in the control subjects (73 ± 77 versus 13 ± 50 pg/ml, p < 0.05), as was the product of the arteriovenous difference in norepinephrine and coronary blood flow (7.3 ± 7.3 versus 0.8 ± 3.0 ng/min, p < 0.05). The slope of the line relating cardiac DHPG production to cardiac norepinephrine spillover was less in the patients with HCM (p < 0.005), indicating that the increased arteriovenous difference in norepinephrine in HCM was not due to increased norepinephrine release (which would have been accompanied by increased DHPG production) but rather due to decreased neuronal uptake and metabolism of norepinephrine. The impairment in cardiac neuronal norepinephrine uptake can explain several morphologic and pathophysiologic features of this disease.

Original languageEnglish
Pages (from-to)836-844
Number of pages9
JournalCirculation
Volume79
Issue number4
DOIs
StatePublished - 1989
Externally publishedYes

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