Rick Schreurs

86 Chapter 5 synchronous and damp each other, while resynchronization may lead to better fusion of the mitral (M1) and tricuspid (T1) component, potentially increasing S1 amplitude. The resultant of these three effects is not well understood. Therefore, the present study was meant to better understand the relation between the SonR1 signal and cardiac pump function in CRT applications. To this purpose, experiments were performed in dogs with synchronous and dyssynchronous heart failure. More specifically, three factors were investigated that may influence the relation between SonR1 and hemodynamic effect: 1) increased contractility, using dobutamine infusion; 2) atrioventricular coupling and 3) interventricular dyssynchrony. METHODS Animal handling was performed in compliance with the Guide for the Care and Use of Laboratory Animals and in accordance with the European Community recommendation. Experiments were performed at Institute Mutualiste Montsouris Recherche in Paris, France. The protocol was approved by the institutional ethics committee. Animal model Experiments were performed in 10 adult dogs of either sex and a bodyweight of 20-25kg. Induction of heart failure After induction with intravenous sodium thiopental, anesthesia was maintained by continuous infusion of midazolam (0,25 mg/kg/h) and sufentanyl (3 μg/kg/h). During a sterile closed chest procedure radiofrequency ablation (MarinR, Medtronic, Heerlen, the Netherlands) was used to create left bundle branch block (LBBB) [11]. Two SonRtip TM leads (Sorin CRM SAS, Clamart, France) were implanted in the right atrium (RA) and the RV apex. The leads were connected to a modified PARADYM TM RF SonR CRT-D pacemaker (Sorin CRM SAS, Clamart, France). In 6 animals tachypacing at the RV (180-200 bpm) for 4-5 weeks was used to induce heart failure. In one animal low contractility was induced in the acute setting using ventilation with isoflurane, one animal had spontaneous low contractility and in one animal heart failure was not induced. Final experiments Sacrifice experiments were performed after 4-5 weeks of tachypacing (n=6) or in the acute setting using the same anesthesia as described above. RV and LV pressure were measured using 7F catheter-tip manometer catheters (CD-Leycom, Zoetermeer, the Netherlands). Two multi-electrode electrophysiological catheters (Medtronic, Heerlen, the Netherlands) were placed transvenously in two different cardiac veins via the coronary sinus for pacing and electrical mapping. Electrocardiograms (ECG) were recorded from the limb leads. Data were acquired at 1000Hz using the IDEEQ Signal Analysis Software (Maastricht Instruments, Maastricht, the Netherlands).