This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During surgery, fluids are given into the blood to compensate for fluid losses and blood loss during surgery. Surgical trauma itself is shown to cause fluid leakage from the vessels and subsequent accumulation of edema. Anesthetic agents also, directly or indirectly, cause changes in blood vessel, heart and kidney functions. Mechanical ventilation during general anesthesia alters hemodynamics and fluid requirements. The current scientific view is that this fluid retention and tissue edema are caused by surgical trauma or mechanical ventilation and not by the administration of an anesthetic per se. However, our research group has conducted two recent studies in sheep that have demonstrated that the combination of isoflurane anesthesia and mechanical ventilation significantly alters the disposition of an infused fluid during anesthesia. Hypothesis: We hypothesize that the same results will be found in humans.
Specific Aims and Procedures: 'The goal of this project is to determine whether isoflurane reduces urinary output and promotes peripheral fluid accumulation after a bolus infusion of intravenous fluid in humans similar to findings earlier described in sheep. To accomplish this objective, we will give a fluid infusion to anesthetized volunteers and frequently sample hemoglobin concentration, which changes in concentration in response to changes in plasma volume. Significance: If corraborated, this would be the first time an anesthetic agent has been proven to alter fluid distribution and thereby promote tissue edema in humans.
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