Pressure-calcium relationships in perfused mouse hearts.

We explored the relationship between left ventricular (LV) pressure and intracellular free calcium concentration ([Ca](i)) in the isolated perfused mouse heart. [Ca](i) (rhod-2) and LV pressure were recorded simultaneously. In response to increases in LV volume (Frank-Starling, FS, protocol), there were increases in developed pressure (up to 250%), with no changes in pressure morphology (rise or relaxation time) or [Ca](i) (magnitude and morphology) for up to 10 min. During transient increases in the stimulus interval at a fixed LV volume (mechanical restitution, MR, protocol), developed pressure increased significantly (31.3 +/- 1.2%), with relatively small changes in peak systolic [Ca](i) (7.4 +/- 1.4%). The relaxation of [Ca](i), however, was prolonged (30.0 +/- 5.5%), resulting in prolonged pressure relaxation (21.2 +/- 1.9%) and increased area under the calcium transient that paralleled the increase in developed pressure (1:1 ratio). A model-based analysis showed that changes in LV pressure during the MR protocol could be completely explained by altered [Ca](i); it was not necessary to invoke any changes in model parameters (i.e., dynamic processes that link calcium to pressure). For the FS data, the model predicted only a change in the gain parameter; however, this change alone cannot reproduce well-established length-dependent changes in the steady-state force-pCa relationship. In summary, the mouse myocardium appears to be unique in that significant changes in peak developed pressure can occur with little or no change in the peak [Ca](i). Additionally, unlike other mammalian species, load-dependent prolongation of pressure relaxation is absent in the mouse heart, and pressure relaxation is primarily governed by intracellular free calcium relaxation.