Why does the cardiac force-velocity relationship not follow a Hill hyperbola? Possible implications of feedback loops involved in cardiac excitation-contraction coupling.

1. If cardiac force-velocity (PV) relationships are determined in a rhythmically beating isolated preparation by progressively changing afterloads, the PV curves obtained exhibit a characteristic nonhyperbolic shape with an upward convexity in the force domain close to P0. It was suggested by others that this might be due to contractile element (CE) shortening against series elastic component (SEC) and/or the early decay of the active state at isometric peak tension. 2. The present investigation performed in isolated cat papillary muscles demonstrates that neither CE shortening against SEC nor the variation of the intensity of the active state can fully account for the nonhyperbolic shape of cardiac PV curves. 3. On the other hand large parts of the remaining deviation could be eliminated if the "progressive loading sequence" (PLS) was replaced for an "interpolated loading sequence" (ILS). Here, the muscle contracts under steady state conditions either isometrically or isotonically (zero load). Single afterloaded test contractions are interpolated after every 10th beat. 4. It is concluded that the nonhyperbolic shape of cardiac PV curves, determined by progressively changing afterloads, is the expression of at least four factors: (i) the existence of displacement dependent variation of excitation-contraction coupling (including the contraction-excitation-contraction recoupling loop), (ii) CE shortening against non CE bound SEC, (iii) a variable active state and (iiii) a fourth unknown mechanism.