國立中山大學學位論文典藏.PDF

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1 Effect of Gastric Vagus Stimulation on the Phrenic Nerves Activity during Respiration and Vomiting in Cat

2 I

3 CPG, 0.79 ± ± ~95 Hz 0.75 ± 0.06sec 2.25 ± 0.13sec 100~110 Hz 0.22 ± 0.03 sec 0.54 ± 0.08 II

4 100~120 Hz 0.74 ± ~150 Hz CPG CPG CPG CPG CPG CPG CPG III

5 The purposes of this study were: (a) to compare the effect of gastric vagal stimulation on phrenic nerve activity during respiration and fictive vomiting, (b) to evaluate the modulatory effect of the central pattern generators (CPGs) for respiration and vomiting following peripheral inputs from gastric vagus. Decerebrate, paralyzed, and ventilated cats were used in this study. Vomiting was induced by electric stimulation of the gastric vagus or injection of emetic drugs (e.g. apomorphine). Fictive vomiting was identified by a characteristic series of synchronous bursts of phrenic nerves and abdominal nerves. During respiratory phase, the average duration of the phrenic nerve activity was 0.79 ± 0.07 second. The average duration of the phrenic cycles was 2.55 ± 0.13 second. Spectral analysis indicated that the phrenic activation had high frequency oscillation of 85~95 Hz. Gastric vagus stimulation (100 Hz, 300 ma) during respiratory phase lead to a deviation of the phrenic duration of seconds. The duration of phrenic cycles was also decreased (reduced 0.25 seconds). The IV

6 spectral distribution of the phrenic neurogram was also shifted during gastric vagal stimulation (dextral to 100~110 Hz). During vomiting phase, the average duration of the phrenic activity was 0.22 ± 0.03 seconds which was shorter than that during respiratory phase. The duration of the phrenic cycle during vomiting was 0.54 ±0.08 second. The major distribution of the power spectrum of the phrenic neurogram during vomiting was 100~120 Hz which is apparently higher than that during the respiratory phase. Gastric vagus stimulation during vomiting showed an averagely increased phrenic cycle (0.74 ± 0.05 seconds), and a shift of its spectral distribution (dextral to 120~150 Hz). These results suggest that vomiting and respiration were controlled by separate CPGs. Since the output of these two CPGs can be modified by a common peripheral signal such as stimulatary input signal from the gastric vagus, it is postulated that these two CPGs might be highly overlaped. Alternatively, they might be equipped with a single neural network while possessing two separate functions. Normally, this naural V

7 network will presume respiratory function, once properly stimulated, such as by injecting apomorphine or by chronic electric stimulation of gastric vagus, functions of this neural network, driving same set of motor fibers (diaphragm and abdominal muscles), will be shifted from respiratory control to vomiting phase control. VI

8 VII

9 VIII

10 vomiting/emesis Borison and Wang 1953 Carpenter 1989 Hornby 2001 Miller 1999 chemotherapy radiotherapy Miller area postrema Borison and Wang 1953 Wang and 1

11 Borison 1952 Miller and Leslie nucleus of the solitary tract (Wang and Borison 1951a 1952 Koga and Fukuda 1992) motion sickness vestibular system Miller and Wilson 1983b Carpenter 1989 Hogan 1990 nausea retching expulsion 2

12 apomorphine gallamine triethiodide 2 mg/kg fictive vomiting Miller et al McCarthy et al. 1974b Miller 1988 Bianchi et al Cohen 1979 Feldman 1986 phrenic motoneurons 3 6 C3~C6 3

13 intercostals motoneurons 1 12 T1~T12 abdominal motoneurons 4 3 T4~L3 inspiratory neurons I neurons expiratory neurons E neurons Bianchi et al early I neurons early E neurons I augmenting I aug neurons E aug neurons pre I neurons late I neurons NTS dorsal respiratory group DRG nucleus ambiguus ventral 4

14 respiratory group VRG Kalia 1981 Duffin and Lipski 1987 Kalia et al VRG C1 1 VRG caudal VRG c VRG C1 obex 2 VRG intermediate VRG i VRG VRG VRG rostral VRG r VRG E aug Bötzinger complex BÖT Cohen 1979 Kalia 1981 BÖT I bulbosponal neurons Fedorko and Merrill 1984 Jiang and Lipski 1990 Merrill and Fedorko 1984 central pattern generators for respiration CPG-R Feldman

15 2 CPG CPG coordinate CO2 Borison Wang Borison and Wang 1949 nucleus of the solitary tract NTS lateral reticular formation Wang and Borison

16 1951b vomiting center Miller et al. Miller and Wilson 1983a Borison Wang Borison Wang 55% 25% Borison Wang 10~15 Miller Borison Wang Miller Miller Borison Wang Miller c-fos AP Miller and Ruggiero

17 Carpenter 1990 central pattern generators CPG CPG convergence CPG Fukuda Koga Fukuda and Koga 1991 the intra-bulbar bundle of the vagal afferents the solitary tract AP the commissural nucleus BÖT mylohyoid muscle glottis rostal caudal transection BÖT area subpostrema BÖT Koga and Fukuda 1992 BÖT 8

18 Fukuda and Koga 1992 area subpostrema BÖT CPG BÖT Fukuda and Koga Koga et al Fukuda Koga Miller et al central pattern generators for vomiting CPG 9

19 Miller et al CPG CPG I bulbospinal neurons Berger 1977 Duffin and Lipski 1987 Euler et al Rikard-Bell et al Miller and Ezure 1992 Miller et al Miller and Yates 1993 Nakazawa et al Nonaka and Miller 1991 E bulbospinal neurons Miller et al

20 inter intracostal muscle McCarthy et al. 1974b Miller et al Koga 1991 Koga and Fukda 1994 Zheng et al CPG CPG CPG CPG CPG 11

21 CPG CPG CPG-R CPG-V 12

22 Halothane Halocarbon Laboratories Apomorphine Hydrochloride Sigma Naloxone Hydrochloride Sigma Gallamine Triethiodide Sigma Heparin Sodium Salt Sigma Capnograph-Oximeter 9000 BCI Datagraph Mode B Lafayette Instrument Differentrial AC Ampiligier A-M Systems Digital Recording Oscilloscope 1604 Gould Digital Storage Oscilloscope DS-203 Pintek Electro Surgical Unit MF-80 Medele Labs Fluonac HL-90 Shin-Ei industries, Inc. Isolated Pulse Stimulator Model 2100 A-M Systems Multimeter 34401A HP Neuro-Corder Model DR-890 NeuroData Instruments Corp. Rodent Ventilator Model 683 Hameg Super Power Suction Unit Model DF-5065 Doctor Friend 13

23 Syringe Pump Model 361 Sage Instruments Temperature Controller Cole-Parmer Instrument Company Terufusion Syringe Pump Model STC-521 Terumo Video Cassette Recoder NV-L25HQ Panasonic MP100A-CE BIOPAC System, Inc. 14

24 kg halotnane Fluonac HL-90 4% halothane halothane 4% halothane % halothane 10 15

25 thyroid cartilage Y 2 halothane Y halothane % CO2 halothane Y Y CO2 BCI Capnograph 9000 CO2 CO2 CO mmhg heparin 16

26 15~20 20~30 90 mm Hg transverse vein 17

27 , stereotaxic instrument dura suction pump halothane halothane 1 2 halothane thermopad YSI series 400 thermistor thermometer 37 18

28 C5 Harvard respirator, Model 683 gallamine triethiodide 5 mg phrenic nerve 19

29 L1 obliquus externus obliquus internus transversus abdominis transversus abdominis the sheath 1 apomorphine hydrochloride 0.5~2 mg/kg naloxone 0.5~2.5 20

30 mg/kg ~25Hz 25 V 10 fictive vomiting FV 1 halothane CO gallamine triethiodide, 5 mg/kg CO2 CO2 38~45 mmhg

31 isolated pulse stimulator, Model 2100, A-M system Inc. 100Hz 300mA apomorphine hydrochloride, 0.5-2mg/kg 16~25 Hz 25 V 10 22

32 5 100 Hz 300 ma bipolar electrode different AC amplifier, Model K KHz Neuro-Corder 23

33 fast Fourier transformation FFT Hz 0~200 Hz ASCII excel excel Student s t test p <

34 CO2 38~45 mmhg 1 I E 24 I + E

35 100 Hz 300 ma ? apomorphine fictive vomiting 3 Miller et al

36 % 27.9% 100 Hz 300 ma

37 % % 6A 85~95 Hz 6B 28

38 100~110 Hz 7A 100~120 Hz 140~160 Hz 7B 120~150 Hz 180~200 Hz 8 130~160 Hz 140~160 Hz 90~120 Hz 90~120 Hz 140~160 Hz 29

39 9 180~200Hz 120~140Hz 120~140Hz 130~150 Hz 8 30

40 1 CPG Miller et al. 1987) 2 85~95 Hz 100~120 Hz Cohen et al CPG CPG 3 CPG 4 85~95 Hz 100~110 Hz 100~120 Hz 120~150 Hz 31

41 CPG CPG CPG CPG CPG CPG CPG , 32

42 100 Hz 300 ma 0.8~1.5 Bruce et al ~1.5 2~3 33

43 200~300 ms McCarthy et al. 1974b Miller 1987 VRG 2 CPG CPG Bianchi et al Miller et al CPG 34

44 CPG VRG CPG CPG Miller and Nonaka 1990 FFT 100~120 Hz Cohen 1992 Bianchi and Grélot Koga et al A Miller et al

45 140~160 Hz 90~120 Hz 130~160 Hz 140~160 Hz 130~160 Hz 90~120 Hz 180~200Hz 130~160 Hz 120~140 Hz 90~120 Hz 130~160 Hz 90~120 Hz 36

46 1 100~120 Hz 85~95 Hz CPG 2 CPG CPG CPG 37

47 Berger A.J. (1977) Dorsal respiratory group neurons in the medulla of cat: spinal projections, responses to lung inflation and superior laryngeal nerve stimulation. Brain Res. 135: Bianchi A. L., Denavit-Saubié M., Champagnat J. (1995) Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters. Physiol. Rev. 75: Borison H. L., and Wang S. C. (1949) Functional localization of central coordinating mechanism for emesis in cat. J. Neurophysiol. 12: Borison H. L., and Wang S. C. (1953) Physiology and pharmacology of vomiting. Pharmacol. Rev. 5: Bruce E. N., Euler C. V., Romaniuk J. K., and Yamashiro S. M. (1982) Bilateral reflex effects on phrenic nerve activity in response to single-shock vagal stimulation. Acta Physiol. Scand. 116: Carpenter D. O. (1989) Central nervous system mechanisms in deglutition and emesis. In: Handbook of physiology; Section: The Gastrointestional system, Vol. I, edit by F. E. Bloom. pp American Physiological Society, Bethesda, Maryland. Carpenter D. O. (1990) Neural mechanisms of emesis. Can. J. Physiol. Pharmacol. 68: Choen M. I. (1979) Neurogenesis of respiratory rhythm in the mammal. Physiol. Rev. 59: Cohen M. I., Miller A. D., Branhardt R., and Shaw C.-F. (1992) Weakness of short-term synchronization among respiratory nerve activities during fictive vomiting. Am. J. Physiol. 263: R339-R347. Duffin J., and Lipski J. (1987) Monosynaptic excitation of thoracic motoneurones 38

48 by inspiratory neurons of the nucleus tractus solitarius in the cat. J. Physiol. 390: Euler C. V., Hayward J. N., Marttila I., and Wyman R. J. (1973) Respiratory neurons of the ventrolateral nucleus of the solitary tract of cat: vagal input, spinal connections and morphological identification. Brain Res. 61: Feldman J. L. (1986) Neurophysiology of breathing in mammals, In: Handbook of physiology; Section: The nervous system, Vol. IV, edited by F. E. Bloom. pp American Physiological Society, Bethesda, Maryland. Fedorko L., and Merrill E. G.. Axonal projections from the rostral expiratory neurons of the Bötzinger complex to medulla and spinal xord in the cat. J. Physiol. 350: Fukuda H., and Koga T. (1991) The Bötzinger complex as the pattern generator for retching and vomiting in the dog. Neurosci. Rew. 12: Fukuda H., and Koga T. (1992) Non-respiratory neurons in the Bötzinger complex exhibiting appropriate firing patterns to generate the emetic act in dogs. Neurosci. Rew. 14: Fukuda H., and Koga T. (1997) Neuronal gagging activity patterns may be generated by neurons in the reticular area dorsomedial to the retrofacial nucleus in dogs. Exp. Brain Res. 113: Hogan C. M. (1990) Advances in the management of nausea and vomiting. Nurs. clin. North Am. 25: Hornby P. J. (2001) Central neurocircuitry associated with emesis. Am. J. Med. 111: 106S-112S. Jiang C., and Lipski J. (1990) Extensive monosynaptic inhibition of ventral respiratory group neurons by augmenting neurons in the Bötzinger complex.. Exp. Brain Res. 81: Kalia M. P. (1981) Anatomical organization of central respiratory neurons. Ann. Rev. Physiol. 43:

49 Kalia M., Feldman J. L., and Cohen M. I. (1979) Afferent projections to the inspiratory neuronal region of the ventrolateral nucleus of the tractus solitarius in the cat. Brain Res. 171: Koga T. (1991) Discharge patterns of bulbar respiratory neurons during retching and vomiting in decerebrate dogs. Jpn. J. Physiol. 41: Koga T., and Fukuda H. (1992) Neurons in the nucleus of the solitary tract mediating inputs from emetic vagal afferents and the area postrema to the pattern generator for the emetic act in dogs. Neurosci. Res. 14: Koga T., and Fukuda H. (1994) Bulbospinal augmenting inspiratory neurons may participate in contractions of the diaphragm during vomiting in decerebrate dogs. Neurosci. Lett. 180: Koga T., Qu R. Y., and Fukuda H. (1998) The central pattern generator for vomiting exist in the reticular area dorsomedial to the retrofacial nucleus in dogs. Exp. Brain Res. 118: McCarthy L. E., Borsion H. L., and Friedlander R. M. (1974) Vomiting: radiographic and oscillographic correlates in the decererate cat. Gastroenterology 67: Merrill E. G., and Fedorko L. (1984) Monosynaptic inhibition of phrenic motoneurons: a ong descending projection from Bötzinger neurons. J. Neurosci. 4: Miller A. D., and Wilson V. J. (1983a) Vomiting center reanalyzed: an electrical stimulation study. Brain Res. 270: Miller A. D., and Wilson V. J. (1983b) Vestibular-induced vomiting after vestibulocerebellar lesions. Brain Behav. Evol. 23: Miller A. D., Ezure K., and Suzuki I. (1985) Control of abdominal muscles by brain stem respiratory neurons in the cat J. Neurophysiol. 54: Miller A. D., Tan L. K., and Suzuki I. (1987) Control of abdominal and Expiratory 40

50 intercostals muscle activity during vomiting: role of ventral respiratory group expiratory neurons. J. Neurophysiol. 57: Miller A. D. (1988) Respiratory muscle control during vomiting. Can. J. Physiol. Pharmacol. 68: Miller A. D., and Nonaka S. (1990) Bötzinger expiratory neurons may inhibit phrenic moroneurons and medullary inspiratory neurons during vomiting. Brain Res. 521: Miller A. D., Nonaka S., Lakos S. F., and Tan L. K. (1990) Diaphragmatic and external intercostals muscle control during vomiting: behavior of inspiratory Bulbospinal neurons. J. Neurophysiol. 63: Miller A. D., and Ezure K. (1992) Behavior of inhibitory and excitatory propriobulbar respiratory neurons during fictive vomiting. Brain Res. 578: Miller A. D., and Yates B. J. (1993) Evaluation of role of upper cervical inspiratory neurons in respiration, emesis and cough. Brain Res. 606: Miller A. D., and Leslie R. A. (1994) The area postrema and vomiting. Front. Neuroendocrinol. 15: Miller A. D., Nonaka S., and Jakus J. (1994) Brain areas essential or non-essential for emesis. Brain Res. 647: Miller A. D., and Ruggiero D. A. (1994) Emetic reflex arc revealed by expression of the immediate-early gene c-fos in the cat. J. Neurosci. 14: Miller A. D., Nonaka S., Siniaia, M. S., and Jakus J. (1995) Mutifunctional ventral respiratory group: Bulbospinal expiratory neurons play a role in pudendal discharge during vomiting. J. Auton. Nerv. Syst. 54: Miller A. D. (1999) Central mechanisms of vomiting. Dig. Dis. Sci. 44: 39S-43S. Nakazawa K., Umezaki T., Zhehg Y., and Miller A. D. (1999) Behaviors of bulbar respiratory interneurons during fictive swallowing and vomiting. Otolaryngol. 41

51 Head. Neck. Surg. 120: Nonaka S., and Miller A. D. (1991) Behavior of upper cervical inspiratory propriospinal neurons during fictive vomiting. J. Neurophysiol. 65: Rikard-Bell G. C., and Bystrzycka E. K., and Nail B. S. (1984) Brainstem projections to the phrenic nucleus: a HRP study in the cat. Brain Res. Bull. 12: Wang S. C., and Borison H. L. (1950) The vomiting center. Phtchiat. 63: Arch. Neuro. Wang S. C., and Borison H. L. (1951a) Copper sulphate emesis: a study of afferent pathways from the gastrointestinal tract. Am. J. Physiol. 164: Wang S. C., and Borison H. L. (1951b) The vomiting center: its destruction by radon implantation in dog medulla oblongata. Am. J. Physiol. 166: Wang S. C., and Borison H. L. (1952) A new concept of organization of the central emetic mechanism: recent studies on the sites of action of apomorphine, copper sulfate and cardiac glycosides. Gastroenterology 22: Zheng Y., Umezaki T., Nakazawa K., and Miller A. D. (1997) Role of pre-inspiratory neurons in vestibular and laryngeal reflexes and in swallowing and vomiting. Neurosci. Lett. 225:

52 I (sec) E (sec) Rc (sec) I/Rc (%) normal 0.79 ± ± ± ± 2.3 I-sti 0.75 ± ± 0.15* 2.25 ± 0.13* 33.5 ± 3.1* I E Rc I+E I-sti I/Rc I E I/Rc E I ± (mean ± S.D.) * p<0.05 (Student s t-test, n=20) 43

53 2 Phr (sec) nphr (sec) cphr (sec) Phr/cPhr (%) 0.22 ± ± ± ± ± ± ± ± ± ± ± ± ± ± 0.05* 0.74 ± 0.05* 27.9 ± 8.1* 0.30 ± ± 0.07* 1.06 ± 0.07* 28.5 ± 6.5* 0.32 ± ± 0.05* 1.26 ± 0.05* 25.7 ± 6.3 Phr nphr cphr + nphr Phr/cPhr Phr cphr nphr Phr/cPhr ± (mean ± S.D.) * p<0.05 (Student s t-test n=20) 44

54 1 I inspiratory phase E expiratory phase Phr. N. phrenic nerve Abd. N. abdominal nerve integrate Phr. N. integrate Abd. N. 45

55 2 100 Hz 300 ma Phr. N. phrenic nerve Sti. pulse integrate Phr. N. 46

56 3 respiration fictive vomiting Phr. N. phrenic nerve Sti. marker Abd. N. abdominal nerve integrate Phr. N. integrate Abd. N. 47

57 4 2 ± (mean ± S.D.) * p<0.05 (Student s t-test n=20) 48

58 5 ± (mean ± S.D.) * p<0.05 (Student s t-test n=20) 49

59 A. B. 6 A 85~95 Hz B 100~110 Hz 20 50

60 A. B. 7 A 100~120 Hz 140~160 Hz B 120~150 Hz 180~200 Hz 20 A. 51

61 B. C. 8 A 130~160 Hz B 140~160 Hz 90~120 Hz C 90~120 Hz 140~160 Hz 15 A. 52

62 B. C. 9 n=3 A 180~200 Hz 120~140 Hz B 120~140 Hz C 130~150 Hz 53

392 Acta Physiol. Sin HRP 6 ( kg) (Nembutal TM, 30 mg/ kg, ip), SN23, h PBS, VECTASHIELD C4 6, ( mm, mm ), 5 %

392 Acta Physiol. Sin HRP 6 ( kg) (Nembutal TM, 30 mg/ kg, ip), SN23, h PBS, VECTASHIELD C4 6, ( mm, mm ), 5 % , Oct. 2001, 53 (5) : 391 395 391 Acta Physiologica Sinica 52HT 3,, (, 250012) : 6 WGA2HRP C5, 52HT FITC, 52HT, 52HT HRP252HT, HRP ( ) 52HT : 52HT ; 52HT : 52HT ; ; ; 52HT ; WGA2HRP : Q473 ; R33213 Projections