Short time-scale LV systolic dynamics: pressure vs. volume clamps and effect of activation

We recently proposed a new model-based approach to quantifying short time-scale left ventricular (LV) systolic dynamics. In this study we examine the hypothesis that the quantitation of LV dynamics using the proposed approach is independent of external mechanical perturbations and the level of activation. Mechanical perturbation independence was assessed in seven isolated ferret hearts in which controlled changes in pressure (pressure clamp) or volume (volume clamp) were introduced at the time of peak isovolumetric pressure (protocol 1), and responses to these clamps were analyzed over the first 16 ms. The model described both pressure- and volume-clamps responses equally well. Model parameters were not different among various pressure clamps, and parameters estimated from volume clamps could accurately predict responses to pressure clamps r2 range: 0.993-0.999; normalized root-mean-square error (NRMSE) range: 2.35-5.86%. To examine activation independence, volume- (4 hearts) and pressure-clamp (4 hearts) responses were obtained and analyzed for baseline and postextrasystolic potentiated beats in a manner similar to protocol 1. The model parameter values estimated from the baseline state accurately predicted responses for the postextrasystolic potentiated state (r2 and NRMSE range for volume-clamp data: 0.989-0.998 and 3.35-6.88%, respectively; r2 and NRMSE range for pressure-clamp data: 0.992-0.996 and 4.26-5.23%, respectively). Thus the proposed approach can dissect the contributions of changes in activation from those due to changes in contractile unit properties on the function of the intact LV.