Relationship Between Na + -Ca 2+ –Exchanger Protein Levels and Diastolic Function of Failing Human Myocardium

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Abstract
Background —In the failing human heart, sarcoplasmic reticulum (SR) calcium handling is impaired, and therefore, calcium elimination and diastolic function may depend on the expression of sarcolemmal Na + -Ca 2+ exchanger. Methods and Results —Force-frequency relations were studied in ventricular muscle strip preparations from failing human hearts (n=29). Protein levels of Na + -Ca 2+ exchanger and SR Ca 2+ -ATPase were measured in the same hearts. Hearts were divided into 3 groups by discriminant analysis according to the behavior of diastolic function when stimulation rate of muscle strips was increased from 30 to 180 min −1 . At 180 compared with 30 min −1 , diastolic force was increased by 160%, maximum rate of force decline was decreased by 46%, and relaxation time was unchanged in group III. In contrast, in group I, diastolic force and maximum rate of force decline did not change, and relaxation time decreased by 20%. Na + -Ca 2+ exchanger was 66% higher in group I than in group III. Na + -Ca 2+ exchanger was inversely correlated with the frequency-dependent rise of diastolic force when stimulation rate was increased ( r =−0.74; P 2+ -ATPase was decreased and Na + -Ca 2+ exchanger unchanged in group III, whereas Na + -Ca 2+ exchanger was increased and SR Ca 2+ -ATPase unchanged in group I. Results with group II hearts were between those of group I and group III hearts. Conclusions —By discriminating failing human hearts according to their diastolic function, we identified different phenotypes. Disturbed diastolic function occurs in hearts with decreased SR Ca 2+ -ATPase and unchanged Na + -Ca 2+ exchanger, whereas increased expression of the Na + -Ca 2+ exchanger is associated with preserved diastolic function.

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