Inhibiting NADPH oxidase protects against long-term memory impairment induced by neonatal sevoflurane exposure in mice.

BACKGROUND: Neonatal exposure to anaesthetics such as sevoflurane has been reported to result in behavioural deficits in rodents. However, while oxidative injury is thought to play an underlying pathological role, the mechanisms of neurotoxicity remain unclear. In the present study, we investigated whether the NADPH oxidase inhibitor apocynin protects against long-term memory impairment produced by neonatal sevoflurane exposure in mice. METHODS: Postnatal day six mice were divided into four groups; (1) non-anaesthesia, (2) intraperitoneal apocynin (50 mg kg(-1)) treatment, (3) 3% sevoflurane exposure for 6 h, and (4) apocynin treatment combined with sevoflurane exposure. Superoxide concentrations and NADPH oxidase expression in the brain were determined using dihydroethidium fluorescence and immunoblotting, respectively. Cleaved caspase-3 immunoblotting was used for the detection of apoptosis, and cytochrome c immunoblotting was performed to evaluate mitochondrial function. Long-term cognitive impairment was evaluated using the fear conditioning test in adulthood. RESULTS: Sevoflurane exposure increased concentrations of superoxide (109%) and the NADPH oxidase subunit p22phox (39%) in the brain, and apocynin abolished these increases. Neonatal sevoflurane exposure caused learning deficits in adulthood. Apocynin also maintained long-term memory function in mice given neonatal sevoflurane exposure, and it reduced apoptosis and decreased cytochrome c concentrations in the brains of these mice. CONCLUSIONS: Apocynin reduces neuronal apoptosis and protects against long-term memory impairment in mice, neonatally exposed to sevoflurane by reducing superoxide concentrations. These findings suggest that NADPH oxidase inhibitors may protect against cognitive dysfunction resulting from neonatal anaesthesia.

Halothane enhances dopamine metabolism at presynaptic sites in a calcium-independent manner in rat striatum.

BACKGROUND: We have previously reported that halothane anaesthesia increases the extracellular concentration of dopamine (DA) metabolites in the rat striatum with no change in DA. Although the metabolism of catecholamines is a source of oxidative stress, there is little information about DA metabolism and anaesthesia. We assessed the mechanism(s) of enhanced DA metabolism induced by halothane. METHODS: Microdialysis probes were implanted into male Sprague-Dawley rats and perfused with artificial cerebrospinal fluid (CSF). The dialysate was injected directly into an HPLC every 20 min. Each group of rats (n=5-7) was administered saline, apomorphine 100 microg kg(-1), pargyline 7.5 or 75 mg kg(-1), reserpine 2 mg kg(-1) or alpha-methyl-p-tyrosine (AMPT) 250 mg kg(-1). Another set of rats was perfused with artificial CSF containing tetrodotoxin (TTX) 1 microM or calcium-free CSF containing 10 mM EGTA. Rats were anaesthetized with halothane 0.5 or 1.5% 1 h after pharmacological treatments. RESULTS: In rats pretreated with apomorphine, despite a decrease in DA concentration, halothane induced a increase in DA metabolites. Pargyline (high dose) and reserpine completely and AMPT partially antagonized the increase in DA metabolites induced by halothane anaesthesia. TTX perfusion reduced the increase in DA, whereas calcium-free CSF perfusion did not. CONCLUSIONS: Our data suggest that halothane accelerates DA metabolism at presynaptic sites by releasing DA from reserpine-sensitive storage vesicles to the cytoplasm in a calcium-independent manner. The metabolic oxidative stress of inhalation anaesthesia requires future investigation.

Rapid fluid infusion therapy decreases the plasma concentration of continuously infused propofol.

BACKGROUND: Rapid fluid infusion therapy to treat hypovolemia in anesthetized patients is a common practical regimen in daily clinical settings. This study investigated the effect of large volume loading on the plasma concentration of propofol (Cp), hemodynamic parameters, hemoglobin concentration (Hb), hematocrit value (Ht) and the bispectral index (BIS). METHODS: Sixty patients were administered propofol using a target-controlled infusion technique. We studied two independent groups. Half of the patients (group F, n = 30) were administered fentanyl, and the other half (group E, n = 30) epidural administration of mepivacaine for analgesia. After achieving a pseudo-steady state of propofol anesthesia, baseline values of blood pressure, heart rate, Hb, Ht, cardiac output, Cp and BIS were measured, and 10 ml/kg Ringer's solution was infused over 15 min. RESULTS: In group F, Cp was significantly decreased from 2.24 (0.69) [mean (SD)] to 2.07 (0.61) microg/ml and in group E from 2.02 (0.98) to 1.75 (0.51) microg/ml immediately after infusion (P < 0.05). The significant reduction lasted until 30 min in group F, whereas, Cp quickly recovered in group E. Cardiac output was increased only in group F. The dilution ratio demonstrated the prolonged diluting effect in group E and the significant correlation with the rate of decrease in Cp (P < 0.0003, R = 0.21). The BIS value showed no significant change immediately after infusion. CONCLUSION: Large volume loading decreased Cp without a significant change in BIS values. The effect of infusion therapy on the depth of anesthesia might be small and usually negligible during propofol anesthesia.