Rick Schreurs

111 Left and right ventricular response to CRT in each measurement, before taking the median of the dogs, to get a generic activation pattern. The benefit of this generic activation pattern is that it was less affected by differences in band placement, heart size and electrodes with insufficient contact in the dogs. A representative baseline simulation was obtained by imposing the ventricular activation pattern measured during the experimental baseline condition, i.e. RV-only pacing with an A-RV delay of 125ms. Systemic vascular resistance was adapted to obtain a mean arterial pressure of 60mmHg and heart rate was set to 80bpm, both similar to the animal experiments. Furthermore, total circulating blood volume was adjusted so that cardiac output was maintained at 5.1L/min. The resulting baseline simulation was used as the starting point for the pacing setting simulations. For each of the 100 pacing delay simulations, the pattern of ventricular activation was changed to the activation pattern measured in the canine experiments and the resulting beat-to-beat changes in ventricular mechanics and hemodynamics were stored until a new hemodynamic steady state was reached. During all pacing simulations, systemic vascular resistance and total circulating blood volume were kept constant in order to quantify the acute effect of pacing-induced changes of ventricular pump mechanics and cardiac hemodynamics. Simulated steady- state dP/dt max values are compared with the experimental measurements. In addition, the simulations extended the animal experiments by providing quantitative insight in the beat- to-beat and steady-state changes of ventricular volumes and cardiac output. RESULTS Baseline characteristics for the AV-blocked dogs are described in Table 1 . Table 1. Baseline characteristics inmedian (range) of dogs during baseline (RV-only, A-RV 125ms pacing) During baseline RV-only pacing Weight (kg) 19.8 (19.4-21.4) MAP (mmHg) 55 (42-71) Systolic Arterial Pressure (mmHg) 70 (62-81) Diastolic Arterial Pressure (mmHg) 45 (31-53) LV dP/dt max (mmHg/s) 1205 (1183-1646) RV dP/dt max (mmHg/s) 520 (345-700) Weeks between AVB and Sacrifice (weeks) 13 (12-21) MAP: mean arterial pressure, LV: left ventricle, RV: right ventricle, AVB: atrioventricular block Electrical effects of altering pacing delay settings Figure 2 shows the typical examples of electrical activation patterns acquired using contact mapping in a dog with AV block during LV pre-excitation, simultaneous RV and LV pacing and RV pre-excitation. In case of extreme pre-excitation, capture in the last paced ventricle was lost due to activation via the contralateral ventricle (indicated by the gray line). 6

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