Fetal exposure to high isoflurane concentration induces postnatal memory and learning deficits in rats.

We developed a maternal fetal rat model to study the effects of isoflurane-induced neurotoxicity on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational day 14 were exposed to 1.3 or 3% isoflurane for 1h. At postnatal day 28, spatial learning and memory of the offspring were examined using the Morris Water Maze. The apoptosis was evaluated by caspase-3 immunohistochemistry in the hippocampal CA1 region. Simultaneously, the ultrastructure changes of synapse in the hippocampal CA1 and dentate gyrus region were observed by transmission electron microscopy (TEM). The 3% isoflurane treatment group showed significantly longer escape latency, less time spent in the third quadrant and fewer original platform crossings in the Morris Water Maze test, significantly increased number and optical densities of caspase-3 neurons. This treatment also produced remarkable changes in synaptic ultrastructure compared with the control and the 1.3% isoflurane groups. There were no differences in the Morris Water Maze test, densities of caspase-3 positive cells, or synaptic ultrastructure between the control and 1.3% isoflurane groups. High isoflurane concentration (3%) exposure during pregnancy caused spatial memory and learning impairments and more neurodegeneration in the offspring rats compared with control or lower isoflurane concentrations.

[Effects of gestational isoflurane exposure on postnatal memory and learning in rats].

OBJECTIVE: To investigate the effects of gestational isoflurane exposure on postnatal memory and learning and growth-associated protein-43 (GAP-43), neuropeptide Y(NPY) expression in the hippocampus of pups. METHODS: Twelve maternal Sprague-Dawley rats at gestation d 18(E18) were randomly divided into isoflurane group (n=6) and control group (n=6). Rats in isoflurane group were exposed to 1.3 % isoflurane for 6 h. For control group, animals breathed in 30 % oxygen and air mixed gas at the same condition. Spatial learning and memory of the offspring were determined with the Morris Water Maze(MWM) after postnatal 4 weeks. The changes of GAP-43 and NPY expression in the hippocampal CA1 region of the pups were determined by immunohistochemistry. RESULTS: In MWM training, the escape latency to platform of the pups in isoflurane group was significantly longer, and the time spent in the third quadrant and times of original platform crossing were less than those of control animals (P<0.05). The number and optical density of GAP-43 and NPY positive neurons in the hippocampus of pups decreased significantly in the isoflurane group compared with the controls (P <0.01). CONCLUSION: Isoflurane exposure in pregnant rats significantly impairs the spatial memory and learning of their pups at a juvenile age, which may be associated with the down-regulation of GAP-43 and NPY in the hippocampus.

Effects of isoflurane exposure during pregnancy on postnatal memory and learning in offspring rats.

Emerging evidence has demonstrated that exposure to anesthetics early in life caused neurohistopathologic changes and persistent behavioral impairments. In this study, a maternal fetal rat model was developed to study the effects of isoflurane exposure during pregnancy on postnatal memory and learning in the offspring. Pregnant rats at gestational day 14 were either exposed to 1.3% isoflurane in a humidified 100% oxygen carrier gas or simply humidified 100% oxygen without any inhalational anesthetic for 2 h every day before delivery. Four weeks later, spatial learning and memory of the offspring were examined using the Morris Water Maze. The expression levels of GAP-43 and NPY in the hippocampal CA1 region of the pups were determined by immunohistochemistry and RT-PCR. Simultaneously, the ultrastructure changes in synapse of the hippocampus were also observed by transmission electron microscopy (TEM). Isoflurane exposure during pregnancy impaired postnatal spatial memory and learning in the offspring as shown by the longer escape latency and the fewer original platform crossings in the Morris Water Maze test. The number and optical densities of GAP-43 and NPY positive cells, as well as the levels of GAP-43 and NPY mRNA, decreased significantly in the hippocampus of isoflurane-exposed pups. Furthermore, TEM studies showed remarkable changes in synaptic ultrastructure of hippocampus. These results indicate that isoflurane exposure during pregnancy could cause postnatal spatial memory and learning impairments in offspring rats, which may be partially explained by the down-regulation of GAP-43 and NPY in the hippocampal area.

Geographic differences in the target-controlled infusion estimated concentration of propofol: bispectral index response curves.

PURPOSE: Variability in drug responses could result from both genetic and environmental factors. Thus, drug effect could depend on geographic location, although regional variation is not generally acknowledged as a basis for stratification. There is evidence that the pharmacokinetic set developed in a European population for the target-controlled infusion (TCI) of propofol does not apply in Chinese patients; however, we are not aware of previous studies comparing the estimated concentration-bispectral index (BIS) response of Caucasian patients in Europe with that of Chinese patients in China. METHODS: The Diprifusor™ TCI pump, incorporating the pharmacokinetic model proposed by Marsh et al., was applied to 30 Caucasian patients in Austria and 30 Chinese patients in China. The estimated plasma concentration (C(p)) of propofol for the two groups was set at 1 µg·mL(-1) and increased by 1 µg·mL(-1) every minute to gradually reach 5 µg·mL(-1) after 5 min. The BIS values were fitted against the estimated C(p) and the predicted effect-site concentration (C(e)) in a sigmoid E(max) model. RESULTS: The sigmoid E(max) curves were shifted significantly to the left in the Chinese group compared with the Austrian group. After 5 min, the BIS value in the Chinese group was lower than in the Austrian group (mean ± standard deviation [SD], 47.2 ± 3.6 vs 63.6 ± 5.4, respectively; P = 0.0006). The estimated C(p) at loss of consciousness (LOC), predicted C(e) at LOC, and time to LOC, were lower in the Chinese group than in the Austrian group (3.3 ± 0.8 µg·mL(-1), 1.6 ± 0.4 µg·mL(-1), 2.8 ± 0.6 min, respectively, vs 4.6 ± 2.8 µg·mL(-1), 2.4 ± 1.5 µg·mL(-1), 3.9 ± 0.5 min, respectively; P < 0.0001). CONCLUSION: When propofol is given using the same TCI protocol, Chinese patients in China lost consciousness faster and at a lower estimated plasma concentration than Caucasians in Austria. Larger studies are needed to map geographically appropriate TCI infusion models.

[Effect and mechanism of ropivacaine on the isolated human umbilical artery].

OBJECTIVE: To investigation the effect of ropivacaine on the contraction of the isolated human umbilical artery and the mechanisms involved. METHODS: Endothelium-denuded human umbilical artery rings obtained from healthy full-term parturients were prepared. Using isometric force transducers and a fluorometer, the effect of ropivacaine in cumulative concentration on the contraction response induced by KCl in the presence or absence of verapamil, or verapamil plus ruthenium red or verapamil plus heparin was observed. Furthermore, the effect of ropivacaine on the contraction response of the artery rings incubated in different concentrations of extracellular Ca(2+) was also observed. RESULTS: Ropivacaine induced a dose-dependent biphasic contractile response of human umbilical artery rings: increasing at concentrations of 1.0 x 10(-5) to 1.0 x 10(-4) mol/L and decreasing from 3.0 x 10(-4) to 3.0 x 10(-3) mol/L, which was inhibited by verapamil, or verapamil plus ruthenium red, or verapamil plus heparin. No difference was found between pre-treatment of verapamil, verapamil plus ruthenium red and verapamil plus heparin. Ropivacaine induced no contractile response in Ca(2+)-free solution and a extracellular Ca(2+) dose-dependent increasing contractile response (1.0 x 10(-4) to 3.0 x 10(-2) mol/L). CONCLUSION: Ropivacaine induced a dose-dependent biphasic contractile response of human umbilical artery rings. The increase in intracellular Ca(2+) concentrations by the extracellular Ca(2+) influx, not by the release from the sarcoplasmic reticulum, is involved in ropivacaine-induced vasoconstriction of human umbilical artery smooth muscle.