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1 Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
* To whom correspondence should be addressed. E-mail: amir{at}bm.technion.ac.il.
Various mechanisms have been suggested to explain the cardiac force-length calcium relationships. The existence of a cooperativity mechanism, whereby cross-bridge (XB) recruitment is affected by the number of active XBs, suggests that the force response to length oscillations should lag behind the length oscillations. Consequently, the oscillatory force response should be larger during shortening than during lengthening. To test this prediction the force responses to large SL oscillations (36.7±16.0nm) at different sarcomere lengths (SLs) (n=6) and frequencies (n=7) were studied, in the intact tetanized trabeculae dissected from the rat right ventricle (n=13). Stable tetanii were obtained by utilizing 30µM cyclopiazonic acid (K-H, [Ca2+]0=6mM, 250C). SL was measured by laser diffraction techniques (Dalsa). Force was measured by silicon strain gauge. The instantaneous dynamic stiffness during the large oscillations was measured by superimposing additional fast (50 or 200Hz) and small amplitude (2.25±0.25nm) oscillations. The force responses lagged behind the SL oscillations at slow frequencies (112±41 msec at 1Hz) and counterclockwise hystereses were obtained in the force-length plane: the force was higher during shortening than during lengthening. The delay in the force response decreased as the frequency of SL oscillation was increased. Clockwise hysteresis, where the force preceded the SL were obtained at frequencies above 4Hz. Similar hystereses characteristics were obtained in the force-SL and stiffness-SL planes. Maximal lag was observed at shortest SL and the delay decreased with sarcomere elongation (131.1±31.7 at 1.78±0.03µm versus 14.7±18.5msec at 1.99±0.015µm). The results establish the ability of the cardiac fiber to adapt XB recruitment to changes in the prevailing loading conditions. The study supports the stipulated existence of a cooperativity mechanism that regulates XB recruitment and highlights an additional method to characterize the regulation of the force-length relationship.
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