showed significantly less injury in rats that received ketamine than in rats that did not (2.35 ± 1.14 vs 4.58 ± 0.50, P < 0.0001). The distance traveled by a marker, expressed as percentage of total intestinal length, in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ± 1.64% in rats that received ketamine (P = 0.017 INTRODUCTIONMesenteric ischemia is a clinical entity with a mortality rate between 60% and 100% that usually requires surgical resection of the necrotic intestinal segment [1] . Although there have been advancements in the treatment of ischemic injury, an ideal treatment has not been defined, and new options should be considered. A promising strategy is the use of anesthetic and sedative agents that might exert protective effects on the injured tissue. Ketamine is an agent that has been recommended for this purpose in clinical situations of sepsis, renal ischemia, cerebral ischemia and serious burn injuries [2][3][4] . The small intestine is very sensitive to ischemic insult [5] . Reperfusion causes additional damage through the release of free radicals, pro-inflammatory cytokines, leukotrienes and other related products [6] . Intestinal Abstract AIM: To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS: T h i r ty m a l e W i s t a r ra t s w e i g h i n g 200-250 g were used. Ischemia was induced by obstructing blood flow in 25% of the total small intestinal length (ileum) with a vascular clamp for 45 min, after which either 60 min or 24 h of reperfusion was allowed. Rats were either anesthetized with pentobarbital sodium (50 mg/kg) or ketamine (100 mg/kg). Control groups received sham surgery. After 60 min of reperfusion, the intestine was examined for morphological alterations, and after 24 h intestinal basic electrical rhythm (BER) frequency was calculated, and intestinal transit determined in all groups. RESULTS: The intestinal mucosa in rats that were anesthetized with ketamine showed moderate alterations such as epithelial lifting, while ulceration and hemorrhage was observed in rats that received pentobarbital sodium after 60 min of reperfusion. Quantitative analysis of structural damage using the Chiu scale

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Intermittent hypoxia (IH), a key feature of sleep apnea, increases the oxygen regulated transcription factor Hypoxia Inducible Factor 1a (HIF1a). Although recognized for its role in IH-dependent changes in cardio-respiratory physiology, it remains unclear how IH-dependent HIF1a signaling affects neurophysiology underlying learning and memory. This study examines how IH affects hippocampal associated learning and memory in wildtype mice and mice heterozygous for the HIF1a gene (HIF1a+/-). In wild-type mice, ten days of IH impaired performance in the Barnes maze increased hippocampal HIF1a and elevated protein carbonyls. These behavioral and biochemical effects of IH were accompanied by a decrease in the N-Methyl-D-Aspartate receptor (NMDAr) and an attenuation of long-term potentiation (LTP) in area CA1. In HIF1a+/-, IH did not impair Barnes maze performance, increase hippocampal HIF1a, or enhance protein carbonyl content. At the network level, IH neither led to a decrease in NMDAr nor impaired LTP. Concurrent antioxidant treatment during IH mitigated the IH-dependent effects on the Barnes maze performance and LTP in wildtype mice. Our findings indicate that IH-dependent HIF1a signaling leads to oxidative stress and reduces NMDAr to impair LTP in area CA1, which contributes to IH-dependent deficits in learning and memory associated with the hippocampus.SignificanceIntermittent Hypoxia is a hallmark of sleep apnea and decreases the threshold for cognitive deficit. We demonstrate that intermittent hypoxia-dependent HIF1a signaling contributes to impairments in hippocampal associated memory. This is co-incidental with HIF1a-mediated alternations in synaptic physiology and increased oxidative stress.Key pointsIntermittent hypoxia (IH) is a hallmark of sleep apnea and is known to cause learning and memory deficits.Hypoxia Inducible Factor 1a (HIF1a), is associated with IH-dependent changes in physiology.IH exposure causes increased hippocampal HIF1a in wild type mice and is associated with elevated oxidative stress, impairments to spatial memory, and suppression of long term potentiation (LTP).IH-dependent suppression of LTP is co-incidental with diminished NMDA receptor contribution to glutamatergic transmission.Following IH, mice heterozygous for HIF1a (HIF1a+/-) do not show an increase in HIF1a and oxidative stress, or changes in either behavior or glutamatergic transmission.

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