The mechanisms underlying the Frank-Starling Law of the heart are still vague. Some studies have suggested that cardiac economy is a function of the sarcomere length, and that the economy increases with the preload. They have related this length dependent economy to the Frank-Starling Law of the heart. Muscle economy is determined by the cross-bridge cycling dynamics. Therefore the study investigated the dependence of the cross-bridge kinetics on the sarcomere length. Force responses to identical ramp shortenings that were imposed at different sarcomere lengths, and the rate of force redevelopment at various sarcomere lengths were investigated. Ramp shortenings of 0.1 micrometer were imposed at the various sarcomere lengths (from 1.85 to 2.1 micrometer). Steady activations and isometric sarcomere lengths were imposed by tetanic contractions, utilizing cyclopiazonic acid that slowed the rate of calcium sequestration by the sarcoplasmic reticulum. Sarcomere length was measured by laser diffraction technique and was controlled by fast servomotor. Results showed four distinct phases in the force response; two phases during the ramp shortenings and two during the muscle-length isometric force redevelopments (after the ramp shortening). The first fast kinetic phases of force decline during the ramp shortening and force redevelopment are attributed to fast changes in the force per cross-bridge. The second slower phases relate to the kinetics of cross-bridge cycling. The second slower rate describes the kinetics that determines the number of force-generating XBs. Interestingly, an identical slow phase response during the ramp shortenings was obtained at all the different sarcomere lengths. This observation negates the suggested length dependent XB dynamics, and strongly suggests that the XBs work asynchronously at constant economy. The Frank-Starling Law is determined by length-dependent modulation of the number of XBs, while the force per XB and the kinetics of XB cycling are length independent.
