Concentration and elongation of attached cross-bridges as pressure determinants in a ventricular model.

A ventricular model based on a muscle model relating sarcomere dynamics to Ca(2+)kinetics was used to establish the relative contribution to pressure development of the two components of cross-bridge dynamics: attached cross-bridge concentration and elongation of its elastic structure. The model was tested by reproduction of experiments reflecting myofibrillar behavior at the ventricular level as well as chamber mechanical properties. It was then used to study cross-bridge behavior independently of Ca(2+)activation, by simulation of flow-clamp experiments at constant Ca(2+)concentration. During the volume ramp, both reduced cross-bridge elongation and decreased concentration by cross-bridge detachment caused a fall of pressure; at end-ejection there was a fast partial increase of pressure by recovery of cross-bridge elongation, and during post-ejection there was a slower pressure change towards the value corresponding to end-ejection volume by cross-bridge reattachment according to the rate of constants of Ca(2+)kinetics. Likewise, during a physiological normal ejection, results showed that a maximal decrease in cross-bridge elongation (Deltah) produced a maximal reduction of ejecting pressure with respect to that at constant cross-bridge elongation (DeltaP), both in simulated beats (DeltaP=20%, Deltah=17%), and in experimentally fitted pressure-volume data from open-chest dogs (DeltaP=43.7+/-3.8%, Deltah=30.7+/-8.3%), Deltah being dependent of peak flow (Deltah=0. 1471 peak flow+6.0788, r=0.72). We conclude that normal ejecting pressure depends not only on cross-bridge concentration, but also on the elongation of its elastic structure, which reduces pressure according to flow.