NDT Advance Access originally published online on July 28, 2006
Nephrology Dialysis Transplantation 2006 21(10):2874-2880; doi:10.1093/ndt/gfl368
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Effects of anaesthesia on fluid and solute transport in a C57BL6 mouse model of peritoneal dialysis
1Research Service, VA Salt Lake City Health Care System 2Department of Medicine and 3Department of Bioengineering, University of Utah, Salt Lake City, UT, USA
Correspondence and offprint requests to: John (Ken) Leypoldt, PhD, Dialysis Program, University of Utah, 85 N. Medical Drive East Room 201, Salt Lake City, UT 84112-5350, USA. Email: ken.leypoldt{at}hsc.utah.edu
Background. Genetically modified mice show promise as animal models for studying the physiology and pathophysiology of the peritoneum during peritoneal dialysis (PD). Methods for evaluation of the functional characteristics of the mouse peritoneum have not been studied extensively, and the effects of anaesthesia on fluid and solute transport in mouse models of PD are unknown.
Methods. A single exchange of dialysis solution was performed in C57BL6 mice by injecting fluid into the peritoneal cavity using a 27-gauge needle and allowing fluid to dwell for 30, 60 or 120 min. Experiments evaluated the effect of ketamine (plus xylazine) anaesthesia on fluid and solute transport; these effects were examined in separate experiments using glucose and mannitol as the osmotic agent added to the injected dialysis solution. After euthanasia, blood was collected, the remaining dialysis solution was drained and their contents analysed for concentrations of the osmotic solute (glucose or mannitol), urea nitrogen (UN), sodium (Na) and a volume marker (fluorescein-labelled albumin) added to the initial, injected dialysis solution. Determined parameters included final volume of dialysis solution (drained plus residual fluid volume), dialysate concentration (D/D0) of glucose (or D/D0 mannitol), dialysate-to-plasma concentration ratio for (D/P) UN and D/P Na and the apparent dialysis solution volume by indicator dilution. Peritoneal permeability-area (PA) values or mass transfer-area coefficients were also calculated for the osmotic solutes.
Results. Final volumes of dialysis solution were higher when mice were anaesthetized with ketamine than in unanaesthetized mice, independent of whether glucose or mannitol was used as the osmotic agent. The increases in final volume were paralleled by higher dialysate concentrations (D/D0 values) and lower calculated PA values for both glucose and mannitol. When using either osmotic agent, anaesthesia also increased plasma glucose concentrations, suggesting that ketamine altered glucose metabolism.
Conclusions. Ketamine anaesthesia in the mouse decreases PA values for glucose and mannitol when used as osmotic agents in PD solutions. The decrease in transperitoneal transport for these osmotic agents increases the final volume of fluid which can be obtained from the peritoneal cavity.
Keywords: D/D0 glucose; D/P sodium; D/P urea; final drained volume; mass transfer-area coefficient; peritoneal permeability