Effects Of Ketamine Combined Anesthetic On The NO-cGMP Signal Pathway In CNS In Miniature Pigs

Ketamine combined anesthetic was an specific combined anesthetic, which was invented byspecific physiological characteristics of miniature pigs. To definite that the impacts of combinedanesthetic and its components on the ATPase transmembrane signal transduction system, cAMPsignal transduction system and NO-cGMP signal transduction system in CNS of the miniature pigs,in order to investigate the major active encephalic regions of its components, and the possiblepathways they involved in the anesthesia mechanism and different encephalic regions.65Bama miniature pigs as the experimental animals were divided into5groups randomly,which intramuscular injected normal saline （10mL）, ketamine （0.07mL/kg）, midazolam（0.2mL/kg）, xylazole （0.25mL/kg） and combined anesthetic combined anesthetic （0.08mL/kg）respectively, and the brain tissues were took in T1period （15min）, T2period （45min） and T3period （75min）respectively. The content of NO and the activity of ATPase, NOS were determinedby absorption spectrometry and the concentration of cGMP and cAMP were determined by ELISA.Results:1.The activities of Na^＋-K^＋-ATPase in cerebrum, hippocampus, thalamus andbrainstem after ketamine anesthesia were obviously decreased48.69%,20.27%,51.18%and36.44%respectively, The activities of Ca^2＋-Mg^2＋-ATPase in cerebrum, cerebellum, thalamus andbrainstem were decreased28.75%、28.59%、64.11%and34.68%respectively, The contents ofcAMP in hippocamp and thalamus were raised41.41%and34.55%respectively, The activities ofNOS in cerebrum was obviously decreased99.02%, The contents of NO in different encephalicregions were decreased52.79%,31.20%,33.09%,52.58%, and26.08%respectively, The contentsof cGMP in cerebrum, cerebellum and hippocampus were decreased28.25%,29.87,40.60%respectively.2.The activities of Na^＋-K^＋-ATPase in cerebrum and hippocampus after midazolam anesthesiawere decreased12.02%and13.06%respectively, The activities of Ca^2＋-Mg^2＋-ATPase in cerebrum,cerebellum, thalamus and brainstem were decreased21.24%,20.67%,51.19%and42.19%respectively, The contents of cAMP in hippocampus was raised76.96%, The activities of NOS incerebrum, cerebellum, hippocampus and brainstem were decreased41.21%,23.04%,18.36%and40.15%respectively, The contents of NO in different encephalic regions were decreased56.04%,28.26%,51.53%,61.85%and39.13%respectively, The contents of cGMP in thalamus weredecreased54.52%.3.The activities of Na^＋-K^＋-ATPase in cerebrum, cerebellum and hippocampus after xylazole anesthesia were decreased12.42%,34.58%and30.01%respectively, The activities of Ca^2＋-Mg^2＋-ATPase in cerebellum, thalamus and brainstem were decreased22.58%,34.68%and47.81%respectively, The contents of cAMP in cerebrum, hippocampus, thalamus and brainstem wereraised18.89%,95.16%,48.98%and34.31%respectively, The activities of NOS in cerebrum,hippocampus, thalamus and brainstem were decreased41.21%,27.86%,30.15%and55.05%respectively, The contents of NO in different encephalic regions were decreased24.81%and38.57%respectively, The contents of cGMP in cerebrum and brainstem were decreased31.88%,35.35%respectively.4.The activities of Na^＋-K^＋-ATPase in different encephalic regions after combined anestheticanesthesia were decreased54.50%,46.59%,39.96%,45.50%and44.06%respectively, Theactivities of Ca^2＋-Mg^2＋-ATPase in cerebrum, cerebellum, hippocampus, thalamus and brainstemwere decreased42.49%,34.75%,33.15%,49.76%and59.68%respectively, The contents of cAMPin hippocampus and thalamus were raised79.38%and50.40%respectively, The activities of NOSin cerebrum, cerebellum, hippocampus and thalamus were decreased37.56%,41.13%,36.72%and12.97%respectively, The contents of NO in cerebrum, cerebellum, hippocampus and thalamuswere decreased51.16%,44.53%,39.95%and30.17%respectively, The contents of cGMP indifferent encephalic regions were decreased38.13%,32.80%,50.35%,56.09%and53.96%.Conclusion:1. Inhibition of combined anesthetic on Na^＋-K^＋-ATPase in cerebrum and hippocampus areinduced by the synergistic effect of ketamine, midazolam and xylazole, Inhibition of combinedanesthetic on Na^＋-K^＋-ATPase in cerebellum and inhibition of combined anesthetic onNa^＋-K^＋-ATPase in thalamus as well as brainstem are induced by the mono-effect of xylazole andketamine, respectively;2. Inhibition of combined anesthetic on Ca^2＋-Mg^2＋-ATPase in cerebellum, thalamus andbrainstem are induced by the synergistic effect of ketamine, midazolam and xylazole, Inhibition ofcombined anesthetic on Ca^2＋-Mg^2＋-ATPase in cerebrum are induced by the synergistic effect ofketamine and midazolam, Inhibition of combined anesthetic on Ca^2＋-Mg^2＋-ATPase in hippocampusis induced by the mono-effect of ketamine;3. mono-effect of xylazole can probably causes combined anesthetic the activition cAMPsignal transduction pathway, while combined anesthetic on cAMP signal transduction pathway inhippocampus and thalamus can be induced by the synergistic effect of ketamine, midazolam andxylazole;4. The signal pathways inhibitions of cerebrum, hippocampus and thalamus NO-cGMP whichwere generated by combined anesthetic are presumably resulted from the synergistic effect ofketamine, midazolam and xylazole, the combined anesthetic caused inhibition of the signalpathway of cerebellum and brainstem NO-cGMP can likely be related to the synergistic effect ofketamine-midazolam and midazolam-xylazole,respectively.