Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preserving renal function.

Contains fulltext : 88860.pdf (publisher's version ) (Closed access)OBJECTIVE: We hypothesized that donor treatment of deceased brain dead donors would lead to a decrease in inflammatory responses seen in brain death and lead to a restoration of kidney function. DESIGN: A standardized slow-induction rat brain death model followed by evaluation of kidney function in an isolated perfused kidney model. SETTINGS: Surgery Research Laboratory, University Medical Center Groningen, the Netherlands. SUBJECTS: Male Fisher rats. INTERVENTIONS: Donor treatment with erythropoietin, carbamylated erythropoietin, which lacks erythropoietic activity, or vehicle. MEASUREMENTS AND MAIN RESULTS: In brain death, carbamylated erythropoietin and, to a lesser extent, erythropoietin were able to decrease the expression of several proinflammatory genes and to decrease the infiltration of polymorphonuclear cells in the kidney. No effect on tubular injury parameters was seen. Kidney function decreased almost by 50% after brain death but was fully restored after treatment with both carbamylated erythropoietin and erythropoietin. CONCLUSIONS: Carbamylated erythropoietin can inhibit the inflammatory response caused by brain death more effectively than erythropoietin, whereas both substances can restore kidney function after brain death.1 april 201

Reduced ischemia-reoxygenation injury in rat intestine after luminal preservation with a tailored solution

Background. The intestine is extremely sensitive to ischemic preservation and reoxygenation injury. Current vascular perfusion and cold storage with University of Wisconsin (UW) solution neglect the intestinal lumen and the ongoing mucosal metabolism during hypothermia. This study was designed to test the effects of luminal preservation with an alternative preservation solution in addition to the common vascular flush with UW solution on graft viability after preservation and ex vivo reoxygenation. Methods. Rat intestine was preserved on ice for 6 hr in UW solution or Williams Medium E with additional buffering, impermeants, and a colloid (WMEplus) after being stapled or after flushing and filling the lumen with the respective preservation solution. Tissue slices were prepared from fresh and preserved intestines and were incubated with oxygen for 6 hr at 37 C to assess the viability after reoxygenation. Results. Directly after preservation, histologic damage was mild and unaffected by preservation strategy. Contrary to luminal preservation, closed preservation resulted in significantly decreased ATP levels compared with control. Reoxygenation aggravated damage and revealed differences between the strategies. Luminal preservation better maintained the ATP levels and histologic integrity (vs. closed preservation) for both solutions. Histomorphologic integrity was superior after preservation with WMEplus (vs. UW solution). Expression of stress responsive genes was least up-regulated in the slices from tissue preserved luminally with WMEplus. Conclusions. In conclusion, preservation and reoxygenation injury can be attenuated by luminal preservation with WMEplus