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Free keywords:
arrhythmia; myocardium; calcium; catecholamines; heart failure; Na+-Ca2+-exchanger
Abstract:
Aims In end-stage heart failure, an alteration in the expression of the Na+-Ca2+ exchanger has been reported. Regulation of its expression is largely unknown. We sought to find out whether Na+-Ca2+ exchanger in human heart failure is regulated by sympathetic activation. In addition, since Na+- Ca2+-exchange is electrogenic, we conjectured whether increased expression of Na+-Ca2+ exchanger is associated with an increased incidence of cardiac arrhythmias. Methods and Results Twenty-three patients suffering from end-stage cardiac failure were examined in the hours preceding cardiac transplantation. Plasma levels of norepinephrine, epinephrine, atrial natriuretic peptide, renin activity, aldosterone, tumour necrosis factor (TNF)-alpha, and TNF-receptors were measured. All parameters were elevated relative to 21 healthy control subjects. As determined by immunoblots, protein levels of the Na+-Ca2+ exchanger were increased by 56% and protein levels of sarcoplasmic reticulum (SR) Ca2+-ATPase were decreased by 20% in left ventricles of the explanted failing hearts. A significant correlation between protein and neurohumoral levels was exclusively found for the Na+-Ca2+ exchanger with norepinephrine (r=0(.)64; P=0(.)01). Recent Holter ECGs revealed that patients with sustained or nonsustained ventricular tachycardia (more than three consecutive beats) had significantly higher Na+-Ca2+ exchanger protein and plasma norepinephrine levels than patients with a maximum of two consecutive beats (Na+-Ca2+ exchanger: 109 +/- 10 vs 83 +/- 7, n = 11 each, P<0(.)05; norepinephrine: 1359 +/- 159 vs 656 +/- 88 pg.ml(-1), n = 9 each, P<0(.)001). Conclusions Sympathetic activation may enhance the expression of Na+-Ca2+ exchanger in end-stage heart failure. The data support the hypothesis that increased Na+-Ca2+-exchange could favour malignant ventricular arrhythmia
