The effect of halothane and pentobarbital sodium on brain ependymal cilia

Cilia

Kulvinder Sikand¹  Chris O’Callaghan² 

[1] Department of Infection, Immunity and Inflammation, Division of Child Health, University of Leicester, Leicester, LE2 7LX, England, UK;Department of Respiratory Medicine, Portex Unit, Institute of Child Health, University College London (UCL) and Great Ormond Street Hospital, 30 Guilford Street, London, WC1N 1EH, England, UK

关键词: Sodium pentobarbitone;    Brain cilia;    Volatile anesthetics;    Halothane;    CSF flow;    CSF;    Cerebrospinal fluid;    Ependymal cilia;    Ependyma;    Ciliary beat frequency;    Cilia;   

Others  :  793445
DOI  :  10.1186/2046-2530-1-12

 received in 2011-09-13, accepted in 2012-07-06,  发布年份 2012

【 摘 要 】

Background

The effect of anesthetic agents on ependymal ciliary function is unknown. The aim of this study was to determine the effect of halothane and pentobarbital sodium on brain ependymal ciliary function.

Methods

We used an ex vivo rat brain slice model to measure ependymal ciliary beat frequency by high speed video photography at 37°C.

Results

Exposure to halothane caused a significant reduction in ciliary beat frequency of 2 % (P = 0.006), 15.5 % (P < 0.001), and 21.5 % (P < 0.001) for halothane concentrations of 1.8 %, 3.4 % and 4.4 %, respectively, compared to controls. Following a one-hour wash-out period, there was no significant difference between control samples and cilia that had been exposed to 1.8 % (P = 0.5) and 3.4 % (P = 0.3) halothane. The beat frequency of cilia exposed to 4.4 % halothane had increased following the wash-out period but cilia were still beating significantly more slowly than cilia from the control group (P = <0.001).

Pentobarbitone at concentrations of 25 and 50 μg/ml had no effect on ciliary beat frequency compared to controls (P = 0.6 and 0.4 respectively). A significant (P = 0.002) decrease in ciliary beat frequency was seen following incubation with a pentobarbitone concentration of 250 μg/ml (mean (SD) frequency, 24(8) Hz compared to controls, 38(9) Hz).

Conclusions

Halothane reversibly inhibits the rate at which ependymal cilia beat. Pentobarbitone has no effect on ciliary activity at levels used for anesthesia. It is unclear whether the slowing of ependymal ciliary by halothane is responsible for some of the secondary central nervous system effects of volatile anesthetic agents.

【 授权许可】

   
2012 O'Callaghan and Sikand; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Del Bigio MR: Ependymal cells: biology and pathology. Acta Neuropathol 2010, 119:55-73.
• [2]Cathcart RS, Jr Worthington WC: Ciliary movement in the rat cerebral ventricles: clearing action and directions of currents. J Neuropathol Exp Neurol 1964, 23:609-618.
• [3]Yamadori T, Nara K: The directions of ciliary beat on the wall of the lateral ventricle and the currents of the cerebrospinal fluid in the brain ventricles. Scan Electron Microsc 1979, 3:335-340.
• [4]Banizs B, Pike MM, Millican CL, Ferguson WB, Komlosi P, Sheetz J, Bell PD, Schwiebert EM, Yoder BK: Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 2005, 132:5329-5339.
• [5]Ibanez-Tallon I, Pagenstecher A, Fliegauf M, Olbrich H, Kispert A, Ketelsen UP, North A, Heintz N, Omran H: Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum Mol Genet 2004, 13:2133-2141.
• [6]Koto M, Adachi J, Shimizu A: A new mutation of primary ciliary dyskinesia (PCD) with visceral inversion (Kartagener’s syndrome) and hydrocephalus. Rat News Lett 1987, 18:14-15.
• [7]Koto M, Miwa M, Shimizu A, Tsuji K, Okamoto M, Adachi J: Inherited hydrocephalus in Csk: Wistar-Imamichi rats; Hyd strain: a new disease model for hydrocephalus. Jikken Dobutsu 1987, 36:157-162.
• [8]Lechtreck KF, Delmotte P, Robinson ML, Sanderson MJ, Witman GB: Mutations in Hydin impair ciliary motility in mice. J Cell Biol 2008, 180:633-643.
• [9]Monkkonen KS, Hakumaki JM, Hirst RA, Miettinen RA, O’Callaghan C, Mannisto PT, Laitinen JT: Intracerebroventricular antisense knockdown of G alpha i2 results in ciliary stasis and ventricular dilatation in the rat. BMC Neurosci 2007, 8:26. BioMed Central Full Text
• [10]Nakamura Y, Sato K: Role of disturbance of ependymal ciliary movement in development of hydrocephalus in rats. Childs Nerv Syst 1993, 9:65-71.
• [11]Hirst RA, Mohammed BJ, Mitchell TJ, Andrew PW, O’Callaghan C: Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated by antipneumolysin antibody. Infect Immun 2004, 72:6694-6698.
• [12]Mohammed BJ, Mitchell TJ, Andrew PW, Hirst RA, O’Callaghan C: The effect of the pneumococcal toxin, pneumolysin on brain ependymal cilia. Microb Pathog 1999, 27:303-309.
• [13]Hirst RA, Gosai B, Rutman A, Guerin CJ, Nicotera P, Andrew PW, O’Callaghan C: Streptococcus pneumoniae deficient in pneumolysin or autolysin has reduced virulence in meningitis. J Infect Dis 2008, 197:744-751.
• [14]Schettini A: Incompatibility of Halogentated Anaesthetics with Brain Surgery. Springer-Verlag, Berlin; 1980.
• [15]Marmarou A, Hochwald G, Nakamura T, Tanaka K, Weaver J, Dunbar J: Brain edema resolution by CSF pathways and brain vasculature in cats. Am J Physiol 1994, 267:H514-H520.
• [16]Dietrich WD, Alonso O, Busto R, Prado R, Dewanjee S, Dewanjee MK, Ginsberg MD: Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats. J Cereb Blood Flow Metab 1996, 16:481-489.
• [17]Maktabi MA, Elbokl FF, Faraci FM, Todd MM: Halothane decreases the rate of production of cerebrospinal fluid. Possible role of vasopressin V1 receptors. Anesthesiology 1993, 78:72-82.
• [18]Mann E, Cookson S, Mann J: Effects of enflurane and halothane on CSF dynamics in the rat. Anesthesiology 1979, 3:S54.
• [19]Artru AA: Relationship between cerebral blood volume and CSF pressure during anesthesia with halothane or enflurane in dogs. Anesthesiology 1983, 58:533-539.
• [20]Kongara K, Chambers J, Johnson C: Effects of tramadol, morphine or their combination in dogs undergoing ovariohysterectomy on peri-operative electroencephalographic responses and post-operative pain. N Z Vet J 2012, 60:129-135.
• [21]Jiang L, Mason GF, Rothman DL, de Graaf RA, Behar KL: Cortical substrate oxidation during hyperketonemia in the fasted anesthetized rat in vivo. J Cereb Blood Flow Metab 2011, 31:2313-2323.
• [22]Hamadate N, Yamaguchi T, Sugawara A, Tsujimatsu A, Izumi T, Yoshida T, Ohmura Y, Yoshioka M: Regulation of cerebral blood flow in the hippocampus by neuronal activation through the perforant path: relationship between hippocampal blood flow and neuronal plasticity. Brain Res 2011, 1415:1-7.
• [23]O’Callaghan C, Atherton M, Karim K, Gyi A, Langton JA, Zamudio I, Barry P: The effect of halothane on neonatal ciliary beat frequency. J Paediatr Child Health 1994, 30:429-431.
• [24]Gyi A, O’Callaghan C, Langton JA: Effect of halothane on cilia beat frequency of ciliated human respiratory epithelium in vitro. Br J Anaesth 1994, 73:507-510.
• [25]Raphael JH, Selwyn DA, Mottram SD, Langton JA, O’Callaghan C: Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro. Br J Anaesth 1996, 76:116-121.
• [26]Nunn JF, Sturrock JE, Wills EJ, Richmond JE, McPherson CK: The effect of inhalational anaesthetics on the swimming velocity of Tetrahymena pyriformis. J Cell Sci 1974, 15:537-554.
• [27]Forbes AR, Gamsu G: Mucociliary clearance in the canine lung during and after general anesthesia. Anesthesiology 1979, 50:26-29.
• [28]Lichtiger M, Landa JF, Hirsch JA: Velocity of tracheal mucus in anesthetized women undergoing gynecologic surgery. Anesthesiology 1975, 42:753-756.
• [29]Manawadu BR, Mostow SR, LaForce FM: Impairment of tracheal ring ciliary activity by halothane. Anesth Analg 1979, 58:500-504.
• [30]Lee KS, Park SS: Effect of halothane, enflurane, and nitrous oxide on tracheal ciliary activity in vitro. Anesth Analg 1980, 59:426-430.
• [31]Sleigh MA: Some aspects of the comparative physiology of cilia. Am Rev Respir Dis 1966, 93(Suppl):16-31.
• [32]Wanner A: Clinical aspects of mucociliary transport. Am Rev Respir Dis 1977, 116:73-125.
• [33]Hirst RA, Rutman A, Sikand K, Andrew PW, Mitchell TJ, O’Callaghan C: Effect of pneumolysin on rat brain ciliary function: comparison of brain slices with cultured ependymal cells. Pediatr Res 2000, 47:381-384.
• [34]O’Callaghan CL, Sikand K, Rutman A, Hirst RA: The effect of viscous loading on brain ependymal cilia. Neurosci Lett 2008, 439:56-60.
• [35]O’Callaghan C, Sikand K, Chilvers M: Analysis of ependymal ciliary beat pattern and beat frequency using high speed imaging: comparison with the photomultiplier and photodiode methods. Cilia 2012. In press
• [36]Rutledge CO, Seifen E, Alper MH, Flacke W: Analysis of halothane in gas and blood by gas chromatography. Anesthesiology 1963, 24:862-867.
• [37]Stoelting RK: Halothane and methoxyflurane concentrations in end-tidal gas, arterial blood, and lumbar cerebrospinal fluid. Anesthesiology 1973, 38:384-388.
• [38]Gregory GA, Eger EI, Munson ES: The relationship between age and halothane requirement in man. Anesthesiology 1969, 30:488-491.
• [39]Lerman J, Robinson S, Willis MM, Gregory GA: Anesthetic requirements for halothane in young children 0–1 month and 1–6 months of age. Anesthesiology 1983, 59:421-424.
• [40]Forbes AR: Halothane depresses mucociliary flow in the trachea. Anesthesiology 1976, 45:59-63.
• [41]Forbes AR, Horrigan RW: Mucociliary flow in the trachea during anesthesia with enflurane, ether, nitrous oxide, and morphine. Anesthesiology 1977, 46:319-321.
• [42]Reinstrup P, Uski T, Messeter K: Influence of halothane and isoflurane on the contractile responses to potassium and prostaglandin F2 alpha in isolated human pial arteries. Br J Anaesth 1994, 72:581-586.
• [43]Koenig HM, Pelligrino DA, Albrecht RF: Halothane vasodilation and nitric oxide in rat pial vessels. J Neurosurg Anesthesiol 1993, 5:264-271.
• [44]Hart JL, Jing M, Bina S, Freas W, Van Dyke RA, Muldoon SM: Effects of halothane on EDRF/cGMP-mediated vascular smooth muscle relaxations. Anesthesiology 1993, 79:323-331.
• [45]Jing M, Bina S, Freas W, Van Dyke RA, Muldoon SM: The interaction of halothane and LY-63583 on nitric oxide induced relaxation of blood vessels. Anaesthesiology 1993, 79:A398.
• [46]Wheeler DM, Katz A, Rice RT, Hansford RG: Volatile anesthetic effects on sarcoplasmic reticulum Ca content and sarcolemmal Ca flux in isolated rat cardiac cell suspensions. Anesthesiology 1994, 80:372-382.
• [47]Yamamoto M, Hatano Y, Kakuyama M, Nakamura K, Tachibana T, Maeda H, Mori K: Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery. Acta Anaesthesiol Scand 1997, 41:376-380.
• [48]Yost S, Owens D, Wingegar B, Forsayeth J, Mayeri E: Concentration dependent hyperpolarisation of identified aplasia neurones by volatile anaesthetics. Anaesthesiology 1993, 79:A396.
• [49]Rockoff MA, Marshall LF, Shapiro HM: High-dose barbiturate therapy in humans: a clinical review of 60 patients. Ann Neurol 1979, 6:194-199.
• [50]Fragen R, Avram M: Barbiturates. Churchill Livingstone, New York; 1994.
• [51]Olsen R: Barbiturates. Int Anesthesiol Clin 1988, 26:254-261.