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CLINICAL STUDY: CARDIAC ARRHYTHMIAS

Age-dependent changes of cardiac neuronal noradrenaline reuptake transporter (uptake₁) in the human heart

Kirsten Leineweber, PhD^*, Thekla Wangemann, Christine Giessler^*, Heike Bruck^*, Stefan Dhein, MD, Martin Kostelka, MD, Friedrich-Wilhelm Mohr, MD, Rolf-Edgar Silber, MD and Otto-Erich Brodde, PhD^*,,*

^* Institute of Pharmacology, Halle, Germany
Clinic for Cardiothoracic Surgery, Martin-Luther-University of Halle-Wittenberg, Halle, Germany
Heart Center, Clinic for Cardiac Surgery, Leipzig, Germany
Departments of Pathophysiology and Nephrology, University of Essen School of Medicine, Essen, Germany

Manuscript received February 19, 2002; revised manuscript received May 7, 2002, accepted June 7, 2002.

^* Reprint requests and correspondence: Dr. Otto-Erich Brodde, Department of Pathophysiology and Nephrology, University of Essen, School of Medicine, Hufelandstr. 55, D-45147, Essen, Germany.
otto-erich.brodde{at}medizin.uni-halle.de

OBJECTIVES: The purpose of this study was to elucidate whether the neuronal noradrenaline reuptake transporter (uptake₁) undergoes age-dependent regulation in the human heart.

BACKGROUND: Aging is associated with various alterations in cardiovascular function.

METHODS: We determined uptake₁ density (by [³H]-nisoxetine binding to membranes) and activity (by accumulation of [³H]-noradrenaline into tissue slices) in the right atria (RA) of 42 patients (age range 3 months to 76 years) undergoing open-heart surgery without apparent heart failure. Moreover, the effects of 1 µmol/l desipramine on the noradrenaline-induced positive inotropic effect were assessed in the isolated, electrically driven RA trabeculae of these patients.

RESULTS: There was a significant negative correlation between RA uptake₁ density and age; moreover, RA uptake₁ activity was significantly reduced in elderly patients. Desipramine (1 µmol/l) significantly shifted noradrenaline concentration-response curves to the left; this shift was significantly more pronounced in younger patients than in older patients.

CONCLUSIONS: With increasing age, human myocardial uptake₁ activity decreases, possibly because of age-dependent downregulation of uptake₁ density.

Abbreviations and Acronyms   RA   right atrium/atria/atrial   NAT   neuronal noradrenaline transporter   NYHA   New York Heart Association

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