These studies investigate the mechanisms by which sarcomere length and force interact dynamically to vary cardiac function. The experiments are guided by, but not restricted to, the working hypothesis that a resistance to shortening results from the initial size of the nonoverlap zone at the ends of the cardiac sarcomere. These I Band Effects are established relatively early in the contractile cycle but predominate later to impede shortening at the end points of cardiac ejection. I. Sarcomere length will be measured by light diffraction in intact, isolated heart muscles. (1) The effect of activation upon the length-dependent fall in the velocity of isotonic shortening will be observed to learn whether a resistance to shortening arises a) within the availability of cross bridges or b) as a secondary effect upon their cycling. (2) Next, rapidly imposed tension or length changes will be imposed to evaluate whether shortening sarcomeres are weaker if initially activated at longer lengths, as predicted by I band effects. The response to stretch and the sarcomere's dynamic properties will be analysed to determine whether the observations can be explained in terms of the cross-bridge cycle. (3) The fall of tension during controlled shortening and vice versa will be observed to estimate the magnitude of an internal resistance to shortening. The dependence upon sarcomere length and steady activation will be determined to learn whether motion's effect orginates in the nonsteady nature of activation or in an I Band Effect. (4) Secondary adjustments in 'end diastolic' length after fixed relengthening, the effect of controlled loading on shortening, and the influence of initial motion on isometric force development will be measured to test functional predictions of I Band Effects. II. Measurements of sarcomere length and contractile tension in directly activated, single cardiac cells will determine whether the effect of initial sarcomere length is established by (5) the myofibril's sensitivity to calcium ion during steady activation, or (6) the effect of length on the removal of calcium ion. Importantly, the influence of motion will be observed under conditions of defined delivery of calcium and where the uniformity of contraction can be directly assessed.
