Rick Schreurs

114 Chapter 6 Changes in simulated cardiac output at different pacing delays While dP/dt max values are regarded as a measure of ventricular contractility, cardiac output may be more closely related to pump function of the entire heart. Note that due to the closed loop circulation, in a steady state situation cardiac output of the RV and LV are the same. Cardiac output was not determined in the experiments, but it was calculated in the model simulations. In these simulations the changes in cardiac output following a switch in pacing delay differed from the changes in both LV and RV dP/dt­ max ( Figure 5 ). Cardiac output was more sensitive to changes in AV-delay than to changes in VV-delay. AV-delays of 50 and 70ms led to the largest increases in cardiac output, amounting up to 9%. Δ RV dP/dt max (%) Δ LV dP/dt max (%) -5 0 10 15 5 10 0 -10 -20 -30 50 50 90 90 130 130 170 170 210 210 50 210 90 170 130 130 170 90 210 50 A-LV A-RV (ms) (ms) Increase in AV-delay LV first | RV first 50 230 50 230 A-LV (ms) A-LV (ms) 50 230 50 230 A-RV (ms) A-RV (ms) -31% 2% -1% 11% -17% 7% -5% 17% Effect of changing VV-delay Computer simulations Effect of changing AV-delay Animal experiments Experiments Simulations Δ RV dP/dt max (%) Δ LV dP/dt max (%) 1 15 0 -10 230 A m - ( s xperi Figure 4. Changes in contractile response as a result of changes in pacing delays in experiments and si mulations. Percentile change from baseline of LV dP/dt max (top) and RV dP/dt max (bottom). The left rows depict the same AV and VV-delay settings as in figure 3 are shown. Heat maps for both the experiment (3 rd column) and simulations (4 th column). Diamonds: Canine measurements (Mean (standard error of the mean) of 6 dogs; Circles: Simulation output. In order to find an explanation for the differences in behavior between cardiac output and RV and LV dP/dt max we compared the time course of these parameters as well as end diastolic volume during the first beats after start of a certain setting, in this case LV pre- excitation ( Figure 6 ). In the first beat after the change in pacing setting and therefore also activation sequence (see above), both LV stroke volume and dP/dt max increased while RV stroke volume and dP/dt max decreased. In the subsequent beat RV end diastolic volume increased, due to the smaller stroke volume of the previous beat, whereas LV end diastolic volume decreased. As a consequence of these end diastolic volume changes, RV stroke volume recovered and LV stroke volume decreased to some extent and in the third and subsequent beats a steady state (SS) was reached, with stroke volume in both ventricles (and therefore cardiac output) increasing by about 3%. This example, representative for