Frank-Starling mechanism retains recirculation fraction of myocardial Ca²⁺ in the beating heart

Myocardial Ca²⁺ handling in excitation-contraction coupling is the second primary determinant of energy or O₂ demand in a working heart. The intracellular and extracellular routes remove myocardial Ca²⁺ that was released into the sarcoplasma with different Ca²⁺: ATP stoichiometries. The intracellular route is twice as economical as the extracellular route. Therefore the fraction of total Ca²⁺ removed via the sarcoplasmic reticulum, i.e., the recirculation fraction of intracellular Ca²⁺ (RF), determines the economy of myocardial Ca²⁺ handling. RF has conventionally been estimated as the exponential decay rate of postextrasystolic potentiation (PESP). However, we have found that PESP usually decays in alternans, but not exponentially in the canine left ventricle beating above 100 beats/min. We have succeeded in estimating RF from the exponential decay component of an alternans PESP. We previously found that the Frank-Starling mechanism or varied ventricular preload did not affect the economy of myocardial Ca²⁺ handling. Then, to account for this important finding, we hypothesized that the Frank-Starling mechanism would not affect RF at a constant heart rate. We tested this hypothesis and found its supportive evidence in 11 canine left ventricles. We conclude that RF at a constant heart rate would remain constant, independent of the Frank-Starling mechanism.