BACKGROUND: The pathophysiology of sepsis is incompletely understood, however alterations in systemic inflammation and serum cytokines are thought to play a central role. In the rat, ketamine, but not isoflurane, prevents hepatic injury from lipopolysaccharide (LPS). The effect of these anesthetics on the systemic inflammatory response and other organs remains to be fully elucidated. We hypothesized that ketamine, but not isoflurane, would blunt the cytokine response to LPS administration. METHODS: Male rats received no anesthesia, intraperitoneal ketamine (70 mg/kg), or inhalational isoflurane. One hour later, LPS (20 mg/kg, intraperitoneal) or saline was given for 5 hours and rats were killed. Gastric fluid volumes were determined as an index of gastric emptying. Serum was collected and cytokines measured via a multiplexed suspension immunoassay. RESULTS: In nonanesthetized rats, LPS increased gastric luminal fluid accumulation and serum levels of proinflammatory cytokines when compared with saline controls. Anesthesia with either ketamine or isoflurane caused a significant reduction in LPS-induced changes in serum cytokines, although ketamine had a more dramatic reduction in tumor necrosis factor alpha levels than did isoflurane. Both anesthetics reduced the interleukin IL-6/IL-10 ratio in response to LPS when compared with LPS alone. Ketamine, but not isoflurane, prevented LPS-induced gastric luminal fluid accumulation. CONCLUSIONS: These data indicate that both ketamine and isoflurane diminish the systemic inflammatory response to LPS in the rat as measured by serum cytokines and a reduced IL-6/IL-10 ratio. However, only ketamine improves LPS-induced gastric dysfunction, perhaps secondary to its ability to reduce serum tumor necrosis factor alpha levels more effectively.
BACKGROUND: The pathophysiology of sepsis is incompletely understood, however alterations in systemic inflammation and serum cytokines are thought to play a central role. In the rat, ketamine, but not isoflurane, prevents hepatic injury from lipopolysaccharide (LPS). The effect of these anesthetics on the systemic inflammatory response and other organs remains to be fully elucidated. We hypothesized that ketamine, but not isoflurane, would blunt the cytokine response to LPS administration. METHODS: Male rats received no anesthesia, intraperitoneal ketamine (70 mg/kg), or inhalational isoflurane. One hour later, LPS (20 mg/kg, intraperitoneal) or saline was given for 5 hours and rats were killed. Gastric fluid volumes were determined as an index of gastric emptying. Serum was collected and cytokines measured via a multiplexed suspension immunoassay. RESULTS: In nonanesthetized rats, LPS increased gastric luminal fluid accumulation and serum levels of proinflammatory cytokines when compared with saline controls. Anesthesia with either ketamine or isoflurane caused a significant reduction in LPS-induced changes in serum cytokines, although ketamine had a more dramatic reduction in tumor necrosis factor alpha levels than did isoflurane. Both anesthetics reduced the interleukin IL-6/IL-10 ratio in response to LPS when compared with LPS alone. Ketamine, but not isoflurane, prevented LPS-induced gastric luminal fluid accumulation. CONCLUSIONS: These data indicate that both ketamine and isoflurane diminish the systemic inflammatory response to LPS in the rat as measured by serum cytokines and a reduced IL-6/IL-10 ratio. However, only ketamine improves LPS-induced gastric dysfunction, perhaps secondary to its ability to reduce serum tumor necrosis factor alpha levels more effectively.
Authors: Peter A Walker; Matthew T Harting; Fernando Jimenez; Shinil K Shah; Shibani Pati; Pramod K Dash; Charles S Cox Journal: Stem Cells Dev Date: 2010-06 Impact factor: 3.272