Page 76 - Effects of radiotherapy and hyperbaric oxygen therapy on oral microcirculation Renee Helmers

Chapter 4
its perfusion in response to IR, the oral microcirculation was measured in vivo using a noninvasive, optical spectroscopic-based handheld imaging system, sidestream dark-field imaging (SDFI). SDFI has extensively been used at the patient bedside and experimental setting to monitor and assess pathophysiological states associated with shock (e.g. cardiogenic, hypovolemic and septic),2,15 interventional endpoints and therapeutic responses associated with microvascular alterations in critical care patients, wound healing and the side effects of cancer chemotherapy and RT.12,13,22 Decreased capillary density, irregular dilatation of blood vessels and telangiectasia were associated with late IR effects in human oral mucosa.13 In the present study parameters coinciding with microvascular blood flow dynamics and microvascular density were examined and compared between baseline and then after IR.
The aim of this study was to develop a pilot translational IR model in which microvascular alterations associated with late IR injury could be measured in rabbit oral mucosa and mandibular bone using SDFI and histological analysis. Microcirculatory changes in vessel density and blood flow were quantified and compared between baseline and after IR. In order to ascertain the translational accuracy of a late IR injury model, we test the hypothesis that cumulative IR dosages equal to 22.4 Gy, 26 Gy, 30 Gy and 32 Gy would result in oral mucosal and mandibular bone histological changes similar to humans.
MATERIALS AND METHODS
The institutional Animal Experimentation Committee of the Academic Medical Center of the University of Amsterdam approved the protocols and guidelines for this study (Ref. No. DFL103187). The care and use of animals were conducted in accordance with the EU Directive 2010/63/EU (22 September 2010) and the Dutch Act on Laboratory Animal Experiments.
Animals
Eight male specific-pathogen-free New Zealand White rabbits (Oryctolagus cuniculus) (Charles River Laboratories France, L’Arbresle Cedex, France) were randomly divided between 4 groups. Each group received a different total IR dose. Mean body weight at start of the study was 2.72±0.16 kg, weighing was carried out weekly throughout the entire period of the study. Animals
74