Isolated cardiac muscle contracting against a real-time model of systemic and pulmonary cardiovascular loads.

Isolated cardiac tissues allow a direct assessment of cardiac muscle function and enable precise control of experimental loading conditions. However, current experimental methods do not expose isolated tissues to the same contraction pattern and cardiovascular loads naturally experienced by the heart. In this study, we implement a computational model of systemic-pulmonary impedance that is solved in real time and imposed on contracting isolated rat muscle tissues. This systemic-pulmonary model represents the cardiovascular system as a lumped-parameter, closed-loop circuit. The tissues performed force-length work-loop contractions where the model output informed both the shortening and restretch phases of each work-loop. We compared the muscle mechanics and energetics associated with work-loops driven by the systemic-pulmonary model with that of a model-based loading method that only accounts for shortening. We obtained results that show simultaneous changes of afterload and preload or end-diastolic length of the muscle, as compared with the static, user-defined preload as in the conventional loading method. This feature allows assessment of muscle work output, heat output, and efficiency of contraction as functions of end-diastolic length. The results reveal the behavior of cardiac muscle as a pump source to achieve load-dependent work and efficiency outputs over a wider range of loads. This study offers potential applications of the model to investigate cardiac muscle response to hemodynamic coupling between systemic and pulmonary circulations in an in vitro setting. We present the use of a "closed-loop" model of systemic and pulmonary circulations to apply, for the first time, real-time model-calculated preload and afterload to isolated cardiac muscle preparations. This method extends current experimental protocols where only afterload has been considered. The extension to include preload provides the opportunity to investigate ventricular muscle response to hemodynamic coupling and as a pump source across a wider range of cardiovascular loads.