Rick Schreurs

137 General discussion delay. With this knowledge, the improvements in stroke during BiV pacing in patients with first degree AV-block as presented in chapter 3 might be even bigger when an optimal VV-delay instead of LV pre-excitation (-40ms) was used. In future, the RV function should therefore be part of AV-optimization strategies. ANIMAL MODELS FOR PACING RESEARCH Animals have been used for research purposes since the development of the pacemaker in the 1950s. Nowadays animals are used to study ventricular dyssynchrony and resynchronization therapy. Main advantage of animal use over patients is that invasive experiments can be more complex and extensive. In chapter 4 for example we were able to measure pressures in all four heart chambers and the aorta and additionally we could also measure flow in the ascending aorta. In chapter 5 the SonR signal could be derived from various locations of the heart while invasive pressure and flow measurements were performed. These invasive measurements are not possible in patients, and thereby give us extra information that cannot be derived from clinical experiments. In this thesis two animal species have been used: dogs and pigs. Historically, dogs have been the species of choice for this kind of research, in particular because ventricular pacing induced a degree of dyssynchrony comparable to humans [50]. On Pubmed the search terms [ventricular dyssynchrony dog/canine] results in 102 hits, where replacing dog/canine by pig/porcine results in 38 hits. However, during recent years the use of dogs for research was banned or avoided due to increasing societal protests. At Maastricht University, dog experiments were stopped just at the onset of this PhD project. This thesis therefore contains data from both species and allows to compare the electrophysiological and hemodynamic consequences of dyssynchrony in both species. In previous canine studies the QRS almost doubled to ~113ms when creating a LBBB [51], but unfortunately these values, obtained at a French research center, were not achieved in chapter 5, possibly because of smaller size and/or different race of the dogs. In pigs ( chapter 4 ) increase in QRS duration due to ventricular pacing was smaller than those in dogs [52]. Maximal IVD during LV pacing in this porcine model was ~18ms, while the IVD in the LBBB or RV-lateral wall paced (mimicking LBBB) canines ( chapter 5 ) were remarkably larger (~33ms). Additionally, it is known that LV dP/dt max improvement as achieved by CRT is significantly larger in canines compared to pigs [53]. These data show that pigs have considerable limitations regarding their use for studies on dyssynchrony, but knowing these limitations, the species can still be of use, for example investigating the effect of prolonged PR-interval ( chapter 3 and chapter 4 ). It is unlikely that dogs can be used again for cardiac research. The present thesis does show that there may be an alternative: computer models like CircAdapt. In chapter 6 we used existing dog 7