Auxotonic Loading of the Cardiac Muscle:

For centuries, the heart has interested scientists. Its function has been studied in experimental setups and by di#erent kinds of validation models. The doctoral study presented in this thesis has been devoted to the development of a mathematical model of the cardiac muscle function based on new experiments on isolated papillary muscles. The goal was to develop a model with minimal complexity in which the model parameters were observable from measured variables. The cardiac muscle works under auxotonic loading conditions, i.e. simultaneous changes in stress and length, while most experiments have been performed under isotonic or isometric conditions or as quick load and length clamps. In order to study the isolated muscle under controlled auxotonic conditions and to perform experiments over a wide range of loading conditions on each individual muscle within a limited time span, we wanted to develop a new measurement and control system for the isolated papillary muscle

Paper B Analysis of the Controlled Auxotonic

In the intact heart, there are simultaneous changes in stress and length throughout the cardiac cycle. In a recently developed digital control system for experiments on isolated papillary muscles from rabbit right ventricle, we included a controlled auxotonic twitch. This twitch allowed proportional changes in stress and length, as if the muscle was acting against an ideal spring. The auxotonic twitches had no discontinuities in length, velocity, stress, or derivative of stress and represented a smooth transition from isotonic to isometric loading. We wanted to use such twitches to analyze the dependence on auxotonic load and initial length of contraction and relaxation. Timing of contraction was independent of load when initial length was l max . Timing of relaxation was highly correlated with peak stress. Twitch prolongation at increased initial length was more pronounced at lower loads. Similar results were obtained when post extra-systolic potentiation was included as an inotropic intervention. The relations between the load dependence of auxotonic contraction and relaxation, presented in this paper, may have implications for the in vivo left ventricular function analysis