Thereby, a third mechanism explaining a lower TRH expression in the face of normal or low thyroid hormone levels could be an increased activity of the available thyroid hormone by increasing the expression of the nuclear selleckchem thyroid hormone receptors. No data on hypothalamic expression of the different thyroid hormone receptors in prolonged critical illness are currently available.Our goal was to study if increased local T3 content in the hypothalamus, brought about by these different potential mechanisms, suppresses hypophysiotropic TRH neurons during prolonged critical illness.Materials and methodsIn vivo animal experimentAll animals were treated according to the Principles of Laboratory Animal Care formulated by the U.S.

National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Institutes of Health. The study protocol was approved by the Leuven University ethical review board for animal research (“type”:”entrez-protein”,”attrs”:”text”:”P03052″,”term_id”:”125522″,”term_text”:”P03052″P03052).The model has been described in detail previously and is shown to reproduce the bi-phasic response to critical illness as seen in the human situation [20,21].Male New Zealand White rabbits were housed individually and exposed to artificial light for 14 hours per day. On day 1, rabbits were anesthetized with 30 mg/kg ketamine, intramuscularly (Merial, Lyon, France), and 0.15 mg/kg medetomidine, intramuscularly (Orion, Ospoo, Finland). Their neck and flanks were shaved and anesthesia was than supplemented by isoflurane (Isoba Vet.

; Schering-Plough, Brussels, Belgium) added to the breathing gas via regular vaporizer. Thereafter, a supplemental local paravertebral block with xylocaine 1% (Astra Pharmaceuticals, Brussels, Belgium) was performed and a full-thickness burn injury equaling 15 to 20% total body surface area was imposed. At the end of the procedure, animals returned to their cages where overnight fluid resuscitation was started with a continuous infusion of Ringer’s lactate at six drops per minute (�� 18 ml/h) through a volumetric infusion pump (IVAC 531 infusion pump, IVAC cooperation, San Diego, CA, USA). All animals received parenteral nutrition (PN) from day 2 onwards to avoid starvation-induced endocrine alterations. The PN infusion bags contained 150 ml of Clinomel N7 (Baxter, Clintec Parent��ral, Maurepas, France) and 175 ml sterile water.

Thus, bags with 325 ml solution contained 156 kcal non-protein calories and 0.99 g nitrogen. Of all non-protein calories, 61.5% were delivered Brefeldin_A as carbohydrates, and 38.5% as fat. Protein intake equaled 1.49 g/kg per day. No additional vitamins or trace elements were added. PN was infused at four drops a minute (�� 12 ml/h). Animals had free access to water, but oral food intake was denied.