CARDIAC NA+ CA2+ EXCHANGE ACTIVITY IN PATIENTS WITH END-STAGE HEART-FAILURE/

Objective: The aim of the present study was to investigate the functio nal activity and expression of the sarcolemmal Na+/Ca2+-exchanger in t he failing human heart. Methods: Left ventricular samples were taken f rom eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by mea suring Na+ gradient-induced Ca-45(2+) transport into sarcolemmal vesic les of quantitatively collected crude membrane preparations. The abund ance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific P-myosin heavy chain protein content. Results: In me mbrane preparations of failing human hearts, both the Na+ gradient-ind uced Ca-45(2+) transport activity and the level of immunoreactive Na+/ Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compa red to controls, respectively. Conclusions: In human end-stage heart f ailure the increased sarcolemmal Na+/Ca2+-exchanger activity appears t o be due to an elevated expression of this protein, An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing huma n heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with me mbrane depolarization and enhanced arrhythmogenesis if the Na+/Ca2+-ex changer operates primarily in the forward mode.