Suppression of Cytokine-lnduced Neutrophil Accumulation in Rat Mesenteric Venules in vivo by General Anesthesia

Abstract

Most studies of neutrophil-endothelial interactions in vivo necessarily require the use of general anesthetic agents which are well known to be immunosuppressive. By using whole-mount preparations of the rat mesoappendix, we were able to study tumor necrosis factor alpha (TNF-α) induced neutrophil adhesion to the mesenteric venular endothelium in vivo without necessarily using general anesthesia. TNF-α significantly increased venular-neutrophil accumulation in a dose-dependent manner; accumulation was markedly increased at 1,2, and 4 h, but returned to baseline after 24 h. After these preliminary dose-response and time-course studies, we evaluated the influence of standard clinically effective doses of several commonly used anesthetic agents (thiopental, pentobarbital, ketamine, α-chloralose, methoxyflurane, and halothane) on the extent of neutrophil-venular accumulation induced 2 h after intraperitoneal injection of 0.4 mg/kg TNF-α, compared to unanesthetized rats. All general anesthetics tested, with the exception of methoxyflurane, significantly suppressed this response. In most cases this suppression was striking (from 60 to 85%) such that a statistically significant proinflammatory response was obscured. Although methoxyflurane also tended to suppress this response to TNF-α, it was the only agent that allowed the response to be clearly seen. Because anesthesia markedly suppresses cytokine-induced neutrophil-venular adhesion, this model should provide an important complementary technique to the classical in vivo microcirculatory approaches which do necessarily require general anesthesia.

The protective effects of ketamine and propofol in obstructive jaundice: an experimental study

“…Similarly, ketamine has been found to reduce the adhesion of exogenously delivered human neutrophils in the guinea pig heart during ischemia-reperfusion (33). Moreover, ketamine has been observed to inhibit neutrophil adhesion in the rat mesentery, possibly due to suppression of E-se lectine which is known to be an adhesion molecule activated by cytokines (34). In summary, based on our results and those of others, ketamine probably reduces lipid peroxidation by neutrophil suppression in rats with obstructive jaundice.…”

Ischemia-Reperfusion Injury in Skeletal Muscle: Comparison of the Effects of Subanesthetic Doses of Ketamine, Propofol, and Etomidate

“…Similarly, ketamine diminished the adhesion of exogenously administered human neutrophils in IRI established in guinea-pig heart [29]. Furthermore, in rat mesenteric arteries, ketamine attenuated neutrophil adhesion, and this effect was suggested to be mediated by the suppression of E-selectin, an adhesion molecule activated by cytokines [30]. Subanesthetic doses of propofol given in the present study attenuated increased malondialdehyde levels seen in IRI group.…”

Inflammatory Cell Infiltration after Endothelin-1-Induced Cerebral Ischemia: Histochemical and Myeloperoxidase Correlation with Temporal Changes in Brain Injury

“…Furthermore, anesthetics including ketamine, pentobarbital, propofol, and halothane have been shown to interact with neutrophils by modulating functions such as chemotaxis, phagocytosis, the accumulation and activation of neutrophils, and the release of superoxide anion Miller et al, 1996;Nishina et al, 1998;Zilberstein et al, 2002). Thus, the accumulation of neutrophils and progression of the neutrophil inflammatory response after cerebral ischemia can be investigated using the ET-1 model without the confounding effects of anesthetics.…”