Interpreting cardiac muscle force-length dynamics using a novel functional model

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Abstract
To describe the dynamics of constantly activated cardiac muscle, we propose that length affects force via both recruitment and distortion of myosin cross bridges. This hypothesis was quantitatively tested for descriptive and explanative validity. Skinned cardiac muscle fibers from animals expressing primarily α-myosin heavy chain (MHC) (mouse, rat) or β-MHC (rabbit, ferret) were activated with solutions from pCa 6.1 to 4.3. Activated fibers were subjected to small-amplitude length perturbations [Δ L( t)] rich in frequency content between 0.1 and 40 Hz. In descriptive validation tests, the model was fit to the ensuing force response [ΔF( t)] in the time domain. In fits to 118 records, the model successfully accounted for most of the measured variation in ΔF( t) ( R2 range, 0.997–0.736; median, 0.981). When some residual variations in ΔF( t) were not accounted for by the model (as at low activation), there was very little coherence (<0.5) between these residual force variations and the applied Δ L( t) input function, indicating that something other than Δ L( t) was causing the measured variation in ΔF( t). With one exception, model parameters were estimated with standard errors on the order of 1% or less. Thus parameters of the recruitment component of the model could be uniquely separated from parameters of the distortion component of the model and parameters estimated from any given fiber could be considered unique to that fiber. In explanative validation tests, we found that recruitment and distortion parameters were positively correlated with independent assessments of the physiological entity they were assumed to represent. The recruitment distortion model was judged to be valid from both descriptive and explanative perspectives and is, therefore, a useful construct for describing and explaining dynamic force-length relationships in constantly activated cardiac muscle.

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