Total Ca²⁺ handling for E-C coupling in the whole heart: An integrative analysis

We assessed total Ca²⁺ handling (transport, flux) in excitation-contraction (E-C) coupling in a beating left ventricle (LV). We developed a new integrative analysis method that utilizes the internal Ca²⁺ recirculation fraction (RF), O₂ consumption (V_O2) for Ca²⁺ handling, and O₂ cost of E_max (contractility index) of the LV. We obtained the RF from the beat constant of the exponential decay component of the postextrasystolic potentiation, and the O₂ cost of E_max from V_O2 measured at different E_max. Our equation calculated the unknown total Ca²⁺ handling, futile Ca²⁺ cycling, and Ca²⁺ reactivity of E_max from the RF and Ca²⁺ handling V_O2. The calculated total Ca²⁺ handling fell between 30 and 110 μmol/kg, depending on E^max and pathological conditions. Our method also allowed an assessment of futile Ca²⁺ cycling and Ca²⁺ reactivity of E_max in a beating LV. These data are not available using conventional methods. Our method can be used to better understand the pathophysiology of total Ca²⁺ handling in a beating heart.