Length-dependent activation in intact ferret hearts: study of steady-state Ca(2+)-stress-strain interrelations

We examined the steady-state stress-strain relationships and the steady-state stress-intracellular calcium concentration ([Ca2+]i) relationship in intact ferret hearts and compared these to previously published analogous relationships in skinned and intact muscle. Langendorff-perfused ferret hearts were treated with ryanodine and tetanized by rapid stimulation to create steady-state conditions. [Ca2+]i was measured concurrently by macroinjected aequorin. Over a range of volumes corresponding to strains between 1.0 and 0.75, steady-state stress decreased by 33% when saturating levels of perfusate calcium were used, indicating the degree to which physical factors contribute to the Frank-Starling relationship. The steady-state stress-[Ca2+]i relationship was sigmoidal with a mean Hill coefficient (nH) of 4.91 +/- 0.29 at a strain of 1.0, and the [Ca2+]i required for half-maximal activation (K1/2) was 0.41 +/- 0.03 microM. K1/2 increased and nH decreased with decreasing strains. These results are similar to those observed in intact muscle but differ quantitatively from results obtained in isolated, skinned preparations. Based on these results, we suggest that whole heart function can be related to average sarcomere function without the need for complex models of ventricular structure.