Load dependence of ventricular performance explained by model of calcium-myofilament interactions.
Although a simple concept of load-independent behavior of the intact heart evolved from early studies of isolated, intact blood-perfused hearts, more recent studies showed that, as in isolated muscle, the mode of contraction (isovolumic vs. ejection) impacts on end-systolic elastance. The purpose of the present study was to test whether a four-state model of myofilament interactions with length-dependent rate constants could explain the complex contractile behavior of the intact, ejecting heart. Studies were performed in isolated, blood-perfused canine hearts with intracellular calcium transients measured by macroinjected aequorin. Measured calcium transients were used as the driving function for the model, and length-dependent rate constants yielding the highest concordance between measured and model-predicted midwall stress at different isovolumic volumes were determined. These length-dependent rate constants successfully predicted contractile behavior on ejecting contractions. This, along with additional model analysis, suggests that length-dependent changes in calcium binding affinity may not be an important factor contributing to load-dependent contractile performance in the intact heart under physiological conditions.
Shimizu
Juichiro
J
Division of Circulatory Physiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Todaka
Koji
K
Burkhoff
Daniel
D
D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D004285:Dogs; D066298:In Vitro Techniques; D007700:Kinetics; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology*
D002118:Calcium