AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 286: H1535-H1545, 2004; doi:10.1152/ajpheart.01029.2003
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Interpreting cardiac muscle force-length dynamics using a novel functional model

Kenneth B. Campbell,1 Murali Chandra,1 Robert D. Kirkpatrick,1 Bryan K. Slinker,1 and William C. Hunter2

1Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington 99163; and 2Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102

Submitted 5 November 2003 ; accepted in final form 11 December 2003

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 {alpha}-myosin heavy chain (MHC) (mouse, rat) or {beta}-MHC (rabbit, ferret) were activated with solutions from pCa 6.1 to 4.3. Activated fibers were subjected to small-amplitude length perturbations [{Delta}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 [{Delta}F(t)] in the time domain. In fits to 118 records, the model successfully accounted for most of the measured variation in {Delta}F(t) (R2 range, 0.997–0.736; median, 0.981). When some residual variations in {Delta}F(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 {Delta}L(t) input function, indicating that something other than {Delta}L(t) was causing the measured variation in {Delta}F(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.

muscle stiffness; cross-bridge recruitment; cross-bridge distortion; model validation; mouse; rat; ferret; rabbit



Address for reprint requests and other correspondence: K. B. Campbell, Dept. of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State Univ., Pullman, WA 99163 (E-mail: cvselkbc{at}vetmed.wsu.edu).




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