Stretching Cardiac Trabeculae Increases the Force by Decreasing the Cross-bridge Weakening Rate in a Velocity Dependent Manner

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Background: Stretch increases the force and decreases energy consumption in skeletal muscle. However, the underlying mechanisms and the effects of stretching cardiac muscle remain elusive. We hypothesized that stretch increases the force by modulating the cross-bridge (XB) cycling rates. Methods: Trabeculae (n=6) were isolated from rat right ventricles. Sarcomere length was measured by laser diffraction and controlled by a fast servomotor. The number of strong XBs (NXB) was quantified by measuring the dynamic stiffness. Ramp stretches (n=42) at different velocities and onset times were imposed on sarcomere isometric twitches. Normalized stress (stiffness) enhancement, σE (KE), was defined as the increase in the stress (stiffness) during stretch normalized by the instantaneous isometric stress (stiffness). Results: Stretches yielded identical increases in σE and KE, implying that the stretch increases force by increasing NXB. A unique linear relationship was observed between the instantaneous normalized stress and stiffness, for all the stretch velocities (1.03±0.078, R2=0.99±0.026), suggesting that the unitary force per XB is constant for all stretch velocities (in contrast, a velocity dependent decrease in the force per XB was obtained during sarcomere shortening, in congruent with previous publication). The rate of σE development depended linearly on the stretch velocity (7.35±1.07 [1/μm]). Interestingly, the rate of σE development was independent of the stretch onset time, indicating that it is not dominated by changes in XB recruitment, but is an inherent property of the strong XB, since the population of available XB varies during the twitch. Conclusions: Constant force per XB, independence on the recruitment rate, and the linear dependence of σE on the stretch velocity, strongly suggest that stretch decreases the rate of XB turnover from strong to weak conformation in a velocity dependent manner.