Norepinephrine and arginine vasopressin increase hepatic but not renal inflammatory activation during hemodynamic resuscitation in a rodent model of brain-dead donors.
Lewis AJM., Rostron AJ., Cork DMW., Kirby JA., Dark JH.
OBJECTIVES: Hypotension that occurs after brain death causes a deterioration in organ function, which in turn restricts the number of organs that can be retrieved and leads to graft dysfunction. The correction of hypotension by the administration of norepinephrine increases the number of organs suitable for retrieval but is associated with cardiac allograft failure. Arginine vasopressin is relatively less cardiotoxic; however, the effect of that drug on intra-abdominal organs is unknown. We used a rodent model and real-time reverse transcription polymerase chain reaction to assess changes in the expression of inflammatory mediators in livers and kidneys that occurred in response to resuscitation with those drugs. MATERIALS AND METHODS: Fifty outbred male Wistar rats were anesthetized, and an intracranial balloon was inserted. In 35 rats, the balloon was inflated to induce brain death and subsequent hypotension. In 20 of those rats, hypotension was corrected with either norepinephrine (n = 10) or vasopressin (n = 10), while the remaining 15 rats received no resuscitation. Brain death was not induced in 15 rats that did not become hypotensive or receive resuscitation. Organs were retrieved 30 minutes, 2 hours, and 5 hours after balloon insertion, and inflammatory activation was assessed via real-time reverse transcription polymerase chain reaction. RESULTS: Significant time-dependent up-regulation of CXC motif chemokine ligand 1, interleukin-1beta, and heme oxygenase 1 occurred after brain death. Significantly greater up-regulation of CXC motif chemokine ligand and interleukin-1beta occurred in the livers of rats that received norepinephrine and vasopressin than in those that received no resuscitation. No increase in the expression of those mediators was noted in the kidneys. CONCLUSIONS: This study showed that both norepinephrine and vasopressin amplified the inflammatory response that followed brain death in the livers, but not the kidneys, of rats in this model.