However, fluid management itself may have an impact on lung and distal organ injury in ALI/ARDS [14,15]. Although fluid restriction may cause distal organ damage [14], selleck chemical MEK162 hypervolemia has been associated with increased lung injury [16,17].RMs seem to be more effective in extrapulmonary ALI/ARDS [9], caused mainly by sepsis [18], than in pulmonary ALI/ARDS. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. As the interaction between volemic status and RMs is not well established, we hypothesized that volemic status would potentiate possible deleterious effects of RMs on lung and distal organs in a model of extrapulmonary lung injury induced by sepsis.

Therefore, we compared the effects of RMs in the presence of hypovolemia, normovolemia, and hypervolemia on arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, IL-6, IL-1��, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis in an experimental model of sepsis-induced ALI.Materials and methodsAnimal preparation and experimental protocolThis study was approved by the Ethics Committee of the Health Sciences Center, Federal University of Rio de Janeiro. All animals received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences, USA.

Sixty-six adult male Wistar rats (270 to 300 g) were kept under specific pathogen-free conditions in the animal care facility at the Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro. In 36 rats, Est,L, histology, and molecular biology were analyzed. The remaining 30 rats were used to evaluate lung W/D ratio. Animals were fasted for 16 hours before the surgical procedure. Following that, sepsis was induced by cecal ligation and puncture (CLP) as described in previous studies [19]. Briefly, animals were anesthetized with sevoflurane and a midline laparotomy (2 cm incision) was performed. The cecum was carefully isolated to avoid damage to blood vessels, and a 3.0 cotton ligature was placed below the ileocecal valve to prevent bowel obstruction. Finally, the cecum was punctured twice with an 18 gauge needle [20] and animals recovered from anesthesia. Soon after surgery, each rat received a subcutaneous injection of 1 ml of warm (37��C) normal saline with tramadol hydrochloride (20 Dacomitinib ��g/g body weight).Figure Figure11 depicts the time-course of interventions.