AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 282: H1081-H1091, 2002; doi:10.1152/ajpheart.00498.2001
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Vol. 282, Issue 3, H1081-H1091, March 2002

Load dependence of ventricular performance explained by model of calcium-myofilament interactions

Juichiro Shimizu, Koji Todaka, and Daniel Burkhoff

Division of Circulatory Physiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

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.

left ventricle; calcium transient; four-state model; excitation-contraction coupling


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