Structural and functional changes associated with failure and recovery of hearts after perfusion with Ca 2+-free medium

Abstract

The electrical and mechanical functions and ultrastructure of isolated rat hearts were studied during perfusion with Ca 2+-free medium and during reperfusion with normal medium following various intervals of Ca 2+-free perfusion. Contractile force declined to zero within 30 s of perfusion with Ca 2+-free medium. No ultrastructural changes were observed within 3 min of Ca 2+-free perfusion; however, separation of the intercalated discs was noted after 5 min or longer of Ca 2+-free perfusion and upon reperfusion with normal medium after 3 min of Ca 2+-free perfusion. The ability of hearts to recover contractile force upon reperfusion with normal medium was dependent upon the duration of the Ca 2+-free perfusion. The resting tension was increased during the Ca 2+-free perfusion and was further increased upon reperfusion with normal medium after 2 min. Reperfusion with normal medium after 5 min or longer of Ca 2+-free perfusion also resulted in contracture of sarcomeres and extensive ultrastructural damage. Irreversible changes in surface electrical activity occurred after 3 to 4 min of Ca 2+-free perfusion. Reducing the Na + concentration of the Ca 2+-free medium delayed failure of contractility, augmented the recovery of contractility, and prevented the separation of the intercalated discs. Reducing the Mg 2+ concentration of the Ca 2+-free medium also delayed failure of contractility but did not affect recovery. Reducing the K + concentration did not alter the time-course of failure but diminished the recovery of contractile force after 3 min of Ca 2+-free perfusion. These results clarify the sequence of structural and functional changes occurring during Ca 2+ deprivation and support the view that extracellular Na + plays a deleterious role during failure of Ca 2+-deprived hearts. It is suggested that isolated heart perfused with Ca 2+-free medium forms an interesting model for studying the pathogenesis of two types of heart failure namely failure due to “intracellular calcium deficiency” and failure due to “intracellular calcium overload”.