Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.

It is concluded that functionally important changes occur in the intracellular Ca2+ handling, leading to the negative force-frequency relationship in terminally failing human myocardium. Interestingly, the negative force-frequency relationship can be restored by agents producing positive inotropic effects by elevation of the intracellular Na+ concentration. These findings suggest that hitherto unknown changes in the intracellular ionic homeostasis occur in the failing human heart. Even though increasing Ca2+i in failing heart cells may be detrimental, increasing Na+bdi may be beneficial through a mechanism independent of an increase in [Ca2+i.