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Regional intercostal activity during coughing and vomiting in decerebrate cats STEVE
ISCOE
Department sf Physiology, Queen 's University, Kingston, Ont., Canada K7L 3N6
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LAUKENT &&LOT D@artement de physislogie et ~urophysdologie,Facukte' des sciences et techniques St. -J&rdrne 13397, Marseille CEDEX 13, France Received May 28, 1992 I s c o ~ ,S., and C J R ~E.~ 1992. , Regional intercostal activity during coughing and vomiting in decerebrate cats. Can. J. Physiol. Pharmacol. 70: 1195 - 1199. Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours. Key tvods : diaphragm, abdominal muscles, intercostal muscles. I s e s ~ ,S . , et GRBLOT,L. 1992. Regional intercostal activity during coughing and vomiting in decerebrate cats. Can. J. Physiol. Pharmacol. 70 : 1195 - 1199. L'activitC dlectrique des muscles intercostaux internes et externes des rCgions moyenne et caudale de la cage thoracique a kt6 CtudiCe chez le chat dCcCrCbrC, ventilk mais non-paralysC, pendant la toux et le vomissement. La toux, CvoquCe par la stimulation Clectrique rCpCtitive des nerfs larynges supCrieurs, est caracteriske par une longue et intense activitk du diaphragme immidiatement suivie par l'activation de la musculature abdominale. Alors que, les muscles intercostaux externes et internes des segments thoraciques moyens dkchargent respectivement en synchronie avec le diaphragme et la sangle abdominale, ceux des segments thoraciques caudaux ne somt activks que pendant la phase abdominale de la toux. Le vomissement, CvoquC par la stimulation Clectrique rCpCtitive des nerfs vagues thoraciques, se caractCrise par une sCrie de coactivations du diaphragme et des muscles abdominaux (phase de haut-le-coeur) ponctuCe par une activitC prolongCe de la sangle abdominale aprks la cessation de I'activitC diaphragmatique (phase d9expulsion). Alors que les muscles intercostaux internes et externes des segments thoraciques caudaux dCchargent pendant les coactivations du diaphragme et de la musculature abdominale, ceux des segments thoraciques moyens sont activCs en opposition de phase avec ces m6mes coactivations. Nos rCsultats rCvklent des differences majeures dans le contrble et la fonction des muscles intercostaux des differents segments thoraciques pendant l'accomplissement de diffirentes activitCs motrices. Mots cckks : diaphragme, muscles abdominaux, muscles intercostaux.
Introduction Spontaneous breathing at rest in humans usually requires little more than the activation and relaxation of the diaphragm. Respiratory muscles, however, also serve such protective functions as coughing and vomiting, the former eliminating noxious material from the respiratory tract, the latter from the upper digestive tract. Both require the coordinated activity of many accessory muscles, including the intercostds. This coordinated behaviour is evident in experimental animals during coughing and vomiting (Bolser 1991; GrClot and Milano 1991; Huhhara et al. 1957; Korphs and Tomori 1979; McCarthy and Borison 1974; Monges et al. 1978). Typically, only activities of mid-thoracic intercostal muscles have been recorded (e.g., McCarthy and Borison 1974) and these have 'classical' discharge patterns: the external intercostal~(EIC) discharge in phase, and the internal intercostals (IIC) out of phase, with the diaphragm. However, in anaesthePrinted in Canada I Imprime au Canada
tized cats making respiratory efforts against an occluded airway, intercostal muscles display considerable variability in discharge patterns, depending on thoracic level (Le Bars and Duron 1984). While EIC of the 6th interspace fire during inspiration and IIC during expiration, both muscles of the 3rd intercostal space discharge during inspiration; in the 9th interspace, both discharge during expiration. These differences may reflect dissimilar roles of intercostal muscles at different thoracic levels (see below; for review see Loring and De Troyer 1985). The principal muscle of inspiration, the diaphragm, is apposed to the lower rib cage (the krea of apposition'); this area is thus exposed to abdominal pressure during respiration (Urmey et al. 1988). Activation of caudal intercostal muscles can prevent outward motion of the lower rib cage by stabilizing it when abdominal pressure increases, owing either to descent of the diaphragm or contraction of the abdominal
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FIG.I . Electromyographic activities from diaphragm (DIA), rectus abdominis (ABD), external intercostal of interspace 6 (EIC,), internal intercostal of interspace 6 (IIC6), external intercostal of interspace 11 (EIC, ,), and internal intercostal of interspace 1 1 (IIC ,) during cough elicited by electrical stimulation of the superior laryng a l nerve. The small spikes preceding cough in the top two traces are stimulus artifacts.
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muscles. This stabilization may increase the diaphragm's effectiveness in decreasing pleural pressure during inspiration. The overall objective of this study was to monitor the discharge patterns of EIC and IIC at different levels during two expulsive functions, coughing and vomiting. Specifically, we hypothesized that during coughing, mid-thoracic intercostal muscles would retain their traditional roles, i.e., EIC would be recruited to generate the larger inspiration and IIC would discharge during the expiratory (compressive and expulsive) phase of the cough. Bath caudal EIC and IIC should, however, fire only during the compressive and expulsive phases. In contrast, during the retching phase of vomiting, caudal intercostal muscles should contract synchrsnously with the abdominal muscles and diaphragm to prevent expansion of the caudal rib cage, thereby preventing a loss of abdominal pressure during retching and expulsion.
Methods Experiments were performed on 8 cats of either sex weighing 2.5 -4 kg, initially anaesthetized with an intramuscular injection of 4-5 mL of alfaxalsne and alfadslone acetate (9 and 3 mg . mL-' respectively; Saffan, Glaxovet) to allow cannulation of the trachea. Anaesthesia was maintained with halothane in Q2 during insertion of arterial and venous cannulae and ligation of the external carotid arteries. The cat was decerebrated at the midcollicular level and then rotated to the supine position. Stimulating electrodes were placed on both superior laryngeal nerves (SLN). Afier instituting mechanical ventilation of the cat with room air, an incision was made in the 6th or 7th intercostal space. The lungs were retracted and pairs of electrodes placed around the vagi just above the diaphragm. After securing the electrode leads to neighbouring tissue with ligatures, the incision was closed. A positive end-expiratory pressure of 3 cmPI,O (1 cmH,Q = 98.1 Pa) was then added to the expiratory line to prevent atelectasis. Electromyographic (EMG) recordings were made from the costal diaphragm, the rectus abdominis, and the mid and caudal thoracic EIC and IIC, using paired varnished copper wires inserted approxi-
mately 2-4 mrn apart. To record the diaphragmatic EM@, paired electrodes were inserted into the costal diaphragm via an incision in, typically, the 7th intercostal space; for abdominal activity, the electrodes were inserted through a small incision in the abdominal wall just lateral to the midline. Electrodes were inserted into the intercostal muscles 3-5 cm medial to the rnidaxillary line. To record from IIC (IIC, or IHC, and IIC,, or IIC, ,), about I cm of the overlying EIC was cut along its inferior edge, reflected rostrally, and removed. The recording electrodes were then inserted into the IIC. Recordings from EIC were made approximately 2 cm medial to the site of recording of IIC. The EIC and HHC were carefully separated with small blunt scissors and a piece of Parafilm inserted between them. The electrodes were then inserted into the EIC above the Parafilm. All exposed surfaces were then covered with warm mineral oil to prevent desiccation. To further reduce the possibility of cross talk, intercostal muscles in the interspaces above and below the sites of recording were denervated by cutting both the external and internal intercostal nerves as medially as possible. Cotton pledgets soaked with local anaesthetic (lidocaine) were inserted at the sites of the sections. All EMG activities were amplified and filtered (8.10 -3 kHz). These signals, along with arterial pressure, were displayed on a chart recorder (Gould TA 2000) and recorded on tape (NeursCorder DRS86). Vomiting was induced with trains of stimuli (10-40 V, 0.9-ms pulse duration, at 40 or BOO HE in a 300-ms train applied every 5W ms) to both intact vagi. Vomiting typically started within 2 min of the onset of stimulation; stimulation was discontinued after 5 min if vomiting had not been elicited. In some cats, we administered an intravenous 'cocktail' sf lsbeline (Sigma Chemical, 1-2 mglkg) , naloxone (Endo Labs, 1-2 mglkg), and metaraminol bitartrate (Aramine, Merck Sharp & Dohme, dose as necessary to prevent lobeline-induced hyptension, typically < I mg * kg-]) to aid in the production of vomiting (Miller ee al. 1987). We applied vagal stimulation or injected the cocktail no more often than every 0.5 h because of refractoriness of the cats to re~eatedstimuli. Coughing was induced by stimulation of SLN (2 -5 V, 0.1-ms pulse duration, 2 - 5 Hz). Coughing was elicited easily and repeatedly and had no refractory period.
Results During control respiratory cycles, intercostal and abdominal activity was usually of very low amplitude or absent. When present, mid-thoracic EIC activity in eupnoea was synchronous with diaphragmatic activity; IIC activity was occasionally present during expiration. Caudal intercostal muscle activity was more variable. These findings are in general agreement with previously published results in decerebrate (Fregosi and Baptlett 1989) and anaesthetized (Greer and Stein 1989; Greer and Martin 1998) cats. Similar results during coughing and vomiting were obtained in dB cats. Coughing was elicited in all cats and vomiting in six. An example of the EMG activities of different respiratory muscles during coughing is shown in Fig. 1. Coughing was characterized by an increased amplitude of diaphragmatic and EICg activity, both of which terminated transiently and then continued into the early part of the expiratory phase, concurrent with massive prolonged bursts of abdominal, IIC6, EICII, and IICBL activity. This persistence of activity is eonsistent with previous results in anaesthetized cats (Van Lunteren et al. 1989). During control respiratory cycles, activity was absent in rectus abdominis, EICI and IIC1,; EIC6 discharged in phase with the diaphragm whereas IIC6 discharged during expiration. (In Fig. 1, the activity in IICBB and EICla after the cough may be contamimation swing to increased activity from the subjacent diaphragm, as described by ]Be Troyer and Ninane (19861.)
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ABD
FIG. 2. Electrsmysgraphi activities from different muscles during vomiting. Traces are as described in Fig. 1, but recordings are from the 5th and 10th interspaces. The large spikes at bottom left are stimlus artifacts.
Vomiting (Fig. 2) consisted of, in this example, a series of six retches (the first six bursts of synchronous diaphragmatic, abdominal, and caudal intercostal activity) followed by a short diaphragmatic burst but prolonged bursts of abdominal and caudal intercostal activity. The discharge patterns during retching differed from those during coughing in two major ways: (i) the diaphragm, rectus abdominis, and caudal intercostal muscles were synchronously active, and (ii) midthoracic EHC and IIC discharged together but out of phase with the other muscles during retching. Some mid-thoracic EIC and %ICactivity, however, was synchronous with diaphragmatic activity, a result similar to that in an early report (Huleuhara et d. 1957). During the expulsion phase, the last cycle of activity, both mid-thoracic intercostal muscles started contracting during the second half of the discharges of the abdominal and caudal intercostals, but only after the cessation of phrenic activity. During control respiratory cycles (not shown), activity of the nondiaphragmatic muscles resembled that during control cycles in Fig. H except that mid-thoracic IIC activity was absent, and low levels of synchronous activity in the caudal intercostals, either in or out of phase with the diaphragm, were present. The timing of the onsets of diaphragmatic, abdominal, and caudal intercostal activity during retching varied within and between cats. En 5 of the 6 cats, the onset of diaphragmatic activity preceded that of the rectus abdominis and the caudal intercostal muscles. In 1 cat in which vomiting was elicited four times, diaphragmatic activity always preceded the activity of the other 6synchronously' active muscles but there was no consistent order of recruitment among them. In I cat, the onset of caudal intercostal activity preceded that of the diaphragm. Precise measurements of the delay between the onset of diaphragmatic activity and those s f the other muscles were difficult because of the presence of low levels of tonic EMG activity (not apparent in the figures at low recorder speed); delays typically ranged between 50 and 150 ms.
Discussion The major finding of this study is as follows: during coughing and vomiting, EIC and EIC at different levels had very different discharge patterns when referred to that of the diaphragm. This result generates two major conclusions. First, because EIC and EIC at one level can discharge in or out of phase with the same muscle at a different level during coughing or vomiting, intercostal muscles at different levels should be considered functionally distinct. Second, because of their dissimilar discharge patterns, the central pattern generators (CPGs) responsible for respiration, coughing, and vomiting exert precise and independent control over the discharges sf different intercostal muscles depending on their axial location. Classically, EIC are believed to elevate the ribs and IHC to lower them. Coactivation would therefore seem to be both ineffective and inefficient. However, function depends not only on which muscle (EIC or IIC) is activated but also on its cephalo-caudal location and on lung - rib cage volume (see koring and De Troyer 1985 for review). De Troyer et d. (1985) have shown, in anaesthetized dogs, that independent contraction of EIC or IIC of interspaces 3 -8 elevates the ribs at functional residual capacity (FWC); as lung - rib cage volume increases, this effect is converted to one En which contraction of either muscle lowers the ribs. Simultaneous contraction of EIC and IIIC produces similar effects. Ninane et al. (1991) have recently confirmed these results. Because we did not control lung volume in our cats, we do not know what effect coactivation of EIC and IIC would have had on rib cage configuration. Moreover, because our cats had open airways, they could not have generated the large transdiaphragmatic pressures typical of vomiting when the glottis is closed (McCarthy and Borison 1974). This large pressure gradient is necessary for retrograde motion sf the gastrointestinal contents. To prevent its dissipation by outward motion of the cau-
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dal rib cage, coactivation of the caudal intercostal muscles is necessary. Although the activation of mid-thoracic IIC between diaphragmatic bursts in our experiments agrees with the results of Hukuhara et al. (1957) and McCarthy and Borison (1974), the timing of mid-thoracic EIC activity does not. In McCarthy and Borison's study, mid-thoracic EIC activity was synchronous with diaphragmatic activity whereas in ours midthoracic EIC discharged together with IIC and between bursts of diaphragmatic activity. The reasons for this discrepancy are unclear; however, the EIC activity McCarthy and Borison recorded may have been pickup of underlying IIC activity. Such contamination is common in recordings of intercostal muscle activity from dogs during even modest respiratory efforts (De Troyer and Ninane 1986) and would be even more likely during the intense activation characteristic of vomiting. The EIC activity in our experiments was unlikely due to pickup of IIC activity because of the insulation placed between the two muscles. Contamination of IIC activity was also limited by removing the overlying EIC muscle and by denervating the adjacent interspaces. In addition, comparisons of EIC and IIC recordings from the same interspace always revealed instances in which one muscle was active when the other muscle was quiescent. Moreover, contamination cannot explain an absence of activity. e.g., the absence of EIC activity synchronous with that of the diaphragm. Lastly, coactivation of EHC and IIC was observed in all 6 cats that vomited. Consequently, we believe that the coactivation of mid-thoracic EIC and IIC was real. Segmental reflexes could also explain the presence of midthoracic EIC activity in phase with that of the diaphragm during vomiting (McCarthy and Borison 1974). Their cats were prone and suspended with their abdomens freely pendant; consequently, larger changes in abdominal configuration could have elicited greater reflex effects on intercostal activity than in our supine cats in whom abdominal motion may have been restricted. Second, and more importantly, in their experiments, cats could close the glottis during retching whereas in our cats, the airway remained open owing to the tracheostomy. Consequently, our cats could not have generated the large subatmospheric intrathoracic pressure swings observed in theirs. These negative pressure swings, by 'sucking in' an intact rib cage, could have elicited greater segmental reflex activation of intercostal muscles to prevent its collapse, thereby generating greater subatmospheric intrathoracic pressures. In addition, De Troyer (1991) has recently shown that rostral EIC are reflexly excited by activation of diaphragmatic afferents; this reflex, too, would have been weaker in our cats with open airways. Segmental reflexes may therefore be extremely important in modulating the discharge patterns of some intercostal muscles during vomiting. While our experimental conditions are not as 'natural' as those of McCarthy and Borison, the reduced pressure swings and, therefore, reduced distortion of the chest wall during retching may have resulted in less, or even no, reflex activation of EIC. Thus, the patterns of EMG activity of the different muscles recorded in our experiments likely better represent the output of the medullary vomiting centre(s). Although caudal EIC and IIC discharged in phase with the diaphragm and abdominal muscles during vomiting, only a third of ventral medullary expiratory neurones projecting to the lower thoracic (T13) or lumbar spinal cord fire synchronously with the diaphragm and abdominal muscles during vomiting (Miller et d. 1987). The discharge patterns of the
majority are, however, consistent with those of mid-thoracic EIC and IIC in this study, and with those of mid-thoracic IIC as described by McCarthy and Borison (1974). Expiratory medullary neurones discharging out of phase with the diaphragm and abdominal muscles may d s o project to inhibitory interneurones, a population of cells constituting as many as 50% of the neurones involved in motor control (Jankowska and Lundberg 1981; Mirkwood et a1. 1988). Medullary expiratory neurones firing in phase with the discharges of caudal intercostal muscles in our cats may project directly to the motoneurones. Interneurones may also exert substantial control over respiratory motoneurones at different spinal levels, thereby accounting for variations in intercostal muscle discharge patterns (Davies et d. 1985). The functional role of mid-thoracic intercostal muscle activation, both EIC and IIC, between diaphragmatic -abdominal coactivations is unclear. Because mid-thoracic IIC activity in anaesthetized dogs always occurs during the expiratory phase of the respiratory cycle (De Troyer m d Ninane 19861, the coactivation of EIC and IIC could, depending on thoracic rib cage volume (Ninane et al. 199I), increase the lengths, and improve the contractility, of the diaphragm and abdominal muscles during the subsequent contraction. The coactivation we observed, therefore, suggests a modification of the output from the respiratory CPG such that mid-thoracic EHC are coactivated with IIC. The influence of segmental reflexes on their activity cannot, however, be discounted. Different CPGs are likely responsible for these distinct behaviours even though the same 'respiratory' neurones and muscles are used. During vomiting, for example, medullary inspiratory premotor neurones of the dorsal respiratory group are inhibited (Bianchi and GrClot B989), yet the phrenic motoneurones to which they project remain active (Milano et al. 1992). Other premotor neurones, i.e., those of a still illdefined vomiting centre, must therefore be driving phrenic motoneurones. Although stimulation of many regions in the medulla can elicit vomiting behaviour, Fukuda and Koga (1991) recently claimed to have localized the vomiting centre to the area subpostrema, the output of which is channelled through neurones in the Botzinger complex, just caudal to the facial nucleus. This conclusion contradicts that of Miller and Wilson (1983), that the site of generation of emesis is distributed within the brainstem. Although neurones of the dorsal respiratory group are inhibited during vomiting (Bianchi and Grklot 1989), bulbospinal neurones of this region are also strongly activated during coughing (Grklot et al. 1991). Neurones of the ventral respiratory group in anaesthetized cats also increase their activity during cough and sneeze (JakuS et al. 1985). These workers found no evidence for activation of a separate pool of neurones subserving cough, a conclusion consistent with the inability of previous workers to localize the vomiting centre by means of electrical stimulation (Miller and Wilson 1983). Nevertheless, our observations that mid-thoracic intercostal muscles discharge in or out of phase with the diaphragm during vomiting and coughing, respectively (and that midthoracic EIC do both during coughing), suggest that distinct functional centres control the discharges of different respiratory muscles during these behaviours.
We thank Professor Yves Jammes for helpful suggestions, Drs. Federico Portillo and Armand Bianchi, and M. Stkphane
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Milano for their assistance. and Mrs. Sheila Gordon for preparing the figures. This research was supported by grants from the Medical Research Council of Canada, the Centre national de la recherche scientifique (Unit6 de recherche associ& 205; France), and la Direction des recherc.es, ktudes et techniques (961168). Bianchi, A. L., and GrClot, L. 1989. Converse motor output of inspiratory bulbospinal premotoneurones during vomiting. Neurosci. Lett. 104: 298 - 302. Bolser, D. 6. 1991. Fictive cough in the cat. J. Appl. Physiol. 71: 2325 -2331. Davies, J. G. McF., Kirkwood, P. A., and Sears, T. A. 1985. The distribution of monosynaptic connexions from inspiratory bulbospinal neurones to inspiratory motoneurones in the cat. J. Physiol. (London), 368: 63 - $7. De Troyer, A. 1991. Differential control of the inspiratory intercostal muscles during airway occlusion in the dog. J. Physiol. (London), 439: 73-88. De Troyer, A., and Ninane, V. 1986. Respiratory function of intercostal muscles in supine dog: an electromyographic study. J. Appl. Physiol. 60: 1692- 1699. De Troyer, A., Kelly, S., Macklem, P. T., and Zin, W. A. 1985. Mechanics of intercostal space and actions of external and internal intercostal muscles. J. Clin. Invest. 75: 850-857. Fregosi, R. F., and Bartlett, D., 9%.1989. Internal intercostal nerve discharges in the cat: influence of chemical stimuli. J. Appl. Physiol. 66: 687-694. F u h d a , H., and Koga, T. 1991. The Botzinger complex as the pattern generator for retching and vomiting in the dog. Neurosci. Res. 12: 471 -485. Greer, J. J., and Martin, T. P. 1990. Distribution of muscle fiber types and EMG activity in cat intercostal muscles. J. Appl. Physiol. 69: 1208- 1211. Greer, J. J., and Stein, R. B. 1989. Length changes of intercostal muscles during respiration in the cat. Respir. Physiol. 78: 309'lqq
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Gr610tq La, and Milano, S . 1991. and muscle activity during coughing in the decerebrate cat. Neuroreport, 2: 165- 168. GrClot, L,, Milano, S.. Portillo, F., and Bianchi, A. L. 1991. Behavior of neural elements of the respiratory network during muscles. In Workshop on neural reflexes involving- respiratory control of movement in vertebrates. Ser. Univ. Fund. ~ u a nMarch, No. 269. p. 66.
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Hukuhara, T., Okada, H., and Yamgami, M. 1957. On the behavior of the respiratory muscles during vomiting. Acta Med. Qkayama, 11: 117-125. J a h S , J. Tomori, Z., and StrAnsky, A. 1985. Activity of bulbar respiratory neurones during cough and other respiratory reflexes in cats. Physiol. Bohemoslov. 34: 127 - 136. Jankowska, E., and Lundberg, A. 1981, Interneurons in the spinal cord. Trends Neurosci. 4: 238 -233. Kirkwood, P. A., Munson, J. B., Sears, T. A., and Westgaard, R. H. 1988. Respiratory interneurones in the thoracic spinal cord of the cat. J. Physiol. (London), 395: 161 - 192. Korpis, J., and Tomori, Z. 19'79. Cough and other respiratory reflexes. Karger , Basel. Le Bars, P., and Duron, B. 1984. Are the external and internal intercostal muscles synergist or antagonist in the cat? Neurosci. Lett. 51: 383-386. Loring, S. W.,and De Troyer, A. 1985. Actions s f the respiratory muscles. Ira The thorax. Edited by 6 . Roussos and P. T. Macldem. Marcel Dekker, New York. pp. 327 -349. McCarthy, L. E., and Borison, H. L. 1974. Respiratory mechanics of vomiting in decerebrate cats. Am. J. Physiol. 226: 738 -743. Milano, S., Grklot, L., Bianchi, A. L., and Iscoe, S. 1992. Discharge patterns of phrenic motoneurons during fictive coughing and vomiting in decerebrate cats. J. Appl. Physiol. In press. Miller, A. D., and Wilson, V. J. 1983. "Vomiting center' reanalyzed: an electrical stimulation study. Brain Res. 270: 154 - 158. Miller, A. D., Tan, L. K., and Suzuki, I. 1987. Control of abdominal and expiratory intercostal muscle activity during vomiting: role of ventral respiratory group expiratory neurons. J. Neurophysiol. 57: 1$54- 1866. Monges, H., Salducci, J., and Naudy , B. 1978. Dissociation between the electrical activity of the diaphragmatic dome and cmra muscular fibers during esophageal distension, vomiting and eructation. J. Physiol. (Paris), 74: 54 1-554. Ninane, V . , Gorini, M., and Estenne, M. 1991. Action of intercostal muscles on the lung in dogs. J. Appl. Physiol. 70: 2388-2394. Urmey, W. F., De Troyer, A., Kelly, K. B., and Loring, S. H. 1988. Pleural pressure increases during inspiration in th@zone of apposition of diaphragm to rib J. Apple physiol, 65: 22072212. Van Lunteren, E., Daniels, R.,Deal, E. C., Jr., and Haxhiu, M. A. 1989. Role of costal and cmral diaphragm and parasternal intercostals during coughing in cats. J. Appl. Physiol. 66: 135- 141.
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Regional intercostal activity during coughing and vomiting in decerebrate cats STEVE
ISCOE
Department sf Physiology, Queen 's University, Kingston, Ont., Canada K7L 3N6
Can. J. Physiol. Pharmacol. Downloaded from www.nrcresearchpress.com by Laurentian University on 09/16/13 For personal use only.
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LAUKENT &&LOT D@artement de physislogie et ~urophysdologie,Facukte' des sciences et techniques St. -J&rdrne 13397, Marseille CEDEX 13, France Received May 28, 1992 I s c o ~ ,S., and C J R ~E.~ 1992. , Regional intercostal activity during coughing and vomiting in decerebrate cats. Can. J. Physiol. Pharmacol. 70: 1195 - 1199. Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours. Key tvods : diaphragm, abdominal muscles, intercostal muscles. I s e s ~ ,S . , et GRBLOT,L. 1992. Regional intercostal activity during coughing and vomiting in decerebrate cats. Can. J. Physiol. Pharmacol. 70 : 1195 - 1199. L'activitC dlectrique des muscles intercostaux internes et externes des rCgions moyenne et caudale de la cage thoracique a kt6 CtudiCe chez le chat dCcCrCbrC, ventilk mais non-paralysC, pendant la toux et le vomissement. La toux, CvoquCe par la stimulation Clectrique rCpCtitive des nerfs larynges supCrieurs, est caracteriske par une longue et intense activitk du diaphragme immidiatement suivie par l'activation de la musculature abdominale. Alors que, les muscles intercostaux externes et internes des segments thoraciques moyens dkchargent respectivement en synchronie avec le diaphragme et la sangle abdominale, ceux des segments thoraciques caudaux ne somt activks que pendant la phase abdominale de la toux. Le vomissement, CvoquC par la stimulation Clectrique rCpCtitive des nerfs vagues thoraciques, se caractCrise par une sCrie de coactivations du diaphragme et des muscles abdominaux (phase de haut-le-coeur) ponctuCe par une activitC prolongCe de la sangle abdominale aprks la cessation de I'activitC diaphragmatique (phase d9expulsion). Alors que les muscles intercostaux internes et externes des segments thoraciques caudaux dCchargent pendant les coactivations du diaphragme et de la musculature abdominale, ceux des segments thoraciques moyens sont activCs en opposition de phase avec ces m6mes coactivations. Nos rCsultats rCvklent des differences majeures dans le contrble et la fonction des muscles intercostaux des differents segments thoraciques pendant l'accomplissement de diffirentes activitCs motrices. Mots cckks : diaphragme, muscles abdominaux, muscles intercostaux.
Introduction Spontaneous breathing at rest in humans usually requires little more than the activation and relaxation of the diaphragm. Respiratory muscles, however, also serve such protective functions as coughing and vomiting, the former eliminating noxious material from the respiratory tract, the latter from the upper digestive tract. Both require the coordinated activity of many accessory muscles, including the intercostds. This coordinated behaviour is evident in experimental animals during coughing and vomiting (Bolser 1991; GrClot and Milano 1991; Huhhara et al. 1957; Korphs and Tomori 1979; McCarthy and Borison 1974; Monges et al. 1978). Typically, only activities of mid-thoracic intercostal muscles have been recorded (e.g., McCarthy and Borison 1974) and these have 'classical' discharge patterns: the external intercostal~(EIC) discharge in phase, and the internal intercostals (IIC) out of phase, with the diaphragm. However, in anaesthePrinted in Canada I Imprime au Canada
tized cats making respiratory efforts against an occluded airway, intercostal muscles display considerable variability in discharge patterns, depending on thoracic level (Le Bars and Duron 1984). While EIC of the 6th interspace fire during inspiration and IIC during expiration, both muscles of the 3rd intercostal space discharge during inspiration; in the 9th interspace, both discharge during expiration. These differences may reflect dissimilar roles of intercostal muscles at different thoracic levels (see below; for review see Loring and De Troyer 1985). The principal muscle of inspiration, the diaphragm, is apposed to the lower rib cage (the krea of apposition'); this area is thus exposed to abdominal pressure during respiration (Urmey et al. 1988). Activation of caudal intercostal muscles can prevent outward motion of the lower rib cage by stabilizing it when abdominal pressure increases, owing either to descent of the diaphragm or contraction of the abdominal
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FIG.I . Electromyographic activities from diaphragm (DIA), rectus abdominis (ABD), external intercostal of interspace 6 (EIC,), internal intercostal of interspace 6 (IIC6), external intercostal of interspace 11 (EIC, ,), and internal intercostal of interspace 1 1 (IIC ,) during cough elicited by electrical stimulation of the superior laryng a l nerve. The small spikes preceding cough in the top two traces are stimulus artifacts.
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muscles. This stabilization may increase the diaphragm's effectiveness in decreasing pleural pressure during inspiration. The overall objective of this study was to monitor the discharge patterns of EIC and IIC at different levels during two expulsive functions, coughing and vomiting. Specifically, we hypothesized that during coughing, mid-thoracic intercostal muscles would retain their traditional roles, i.e., EIC would be recruited to generate the larger inspiration and IIC would discharge during the expiratory (compressive and expulsive) phase of the cough. Bath caudal EIC and IIC should, however, fire only during the compressive and expulsive phases. In contrast, during the retching phase of vomiting, caudal intercostal muscles should contract synchrsnously with the abdominal muscles and diaphragm to prevent expansion of the caudal rib cage, thereby preventing a loss of abdominal pressure during retching and expulsion.
Methods Experiments were performed on 8 cats of either sex weighing 2.5 -4 kg, initially anaesthetized with an intramuscular injection of 4-5 mL of alfaxalsne and alfadslone acetate (9 and 3 mg . mL-' respectively; Saffan, Glaxovet) to allow cannulation of the trachea. Anaesthesia was maintained with halothane in Q2 during insertion of arterial and venous cannulae and ligation of the external carotid arteries. The cat was decerebrated at the midcollicular level and then rotated to the supine position. Stimulating electrodes were placed on both superior laryngeal nerves (SLN). Afier instituting mechanical ventilation of the cat with room air, an incision was made in the 6th or 7th intercostal space. The lungs were retracted and pairs of electrodes placed around the vagi just above the diaphragm. After securing the electrode leads to neighbouring tissue with ligatures, the incision was closed. A positive end-expiratory pressure of 3 cmPI,O (1 cmH,Q = 98.1 Pa) was then added to the expiratory line to prevent atelectasis. Electromyographic (EMG) recordings were made from the costal diaphragm, the rectus abdominis, and the mid and caudal thoracic EIC and IIC, using paired varnished copper wires inserted approxi-
mately 2-4 mrn apart. To record the diaphragmatic EM@, paired electrodes were inserted into the costal diaphragm via an incision in, typically, the 7th intercostal space; for abdominal activity, the electrodes were inserted through a small incision in the abdominal wall just lateral to the midline. Electrodes were inserted into the intercostal muscles 3-5 cm medial to the rnidaxillary line. To record from IIC (IIC, or IHC, and IIC,, or IIC, ,), about I cm of the overlying EIC was cut along its inferior edge, reflected rostrally, and removed. The recording electrodes were then inserted into the IIC. Recordings from EIC were made approximately 2 cm medial to the site of recording of IIC. The EIC and HHC were carefully separated with small blunt scissors and a piece of Parafilm inserted between them. The electrodes were then inserted into the EIC above the Parafilm. All exposed surfaces were then covered with warm mineral oil to prevent desiccation. To further reduce the possibility of cross talk, intercostal muscles in the interspaces above and below the sites of recording were denervated by cutting both the external and internal intercostal nerves as medially as possible. Cotton pledgets soaked with local anaesthetic (lidocaine) were inserted at the sites of the sections. All EMG activities were amplified and filtered (8.10 -3 kHz). These signals, along with arterial pressure, were displayed on a chart recorder (Gould TA 2000) and recorded on tape (NeursCorder DRS86). Vomiting was induced with trains of stimuli (10-40 V, 0.9-ms pulse duration, at 40 or BOO HE in a 300-ms train applied every 5W ms) to both intact vagi. Vomiting typically started within 2 min of the onset of stimulation; stimulation was discontinued after 5 min if vomiting had not been elicited. In some cats, we administered an intravenous 'cocktail' sf lsbeline (Sigma Chemical, 1-2 mglkg) , naloxone (Endo Labs, 1-2 mglkg), and metaraminol bitartrate (Aramine, Merck Sharp & Dohme, dose as necessary to prevent lobeline-induced hyptension, typically < I mg * kg-]) to aid in the production of vomiting (Miller ee al. 1987). We applied vagal stimulation or injected the cocktail no more often than every 0.5 h because of refractoriness of the cats to re~eatedstimuli. Coughing was induced by stimulation of SLN (2 -5 V, 0.1-ms pulse duration, 2 - 5 Hz). Coughing was elicited easily and repeatedly and had no refractory period.
Results During control respiratory cycles, intercostal and abdominal activity was usually of very low amplitude or absent. When present, mid-thoracic EIC activity in eupnoea was synchronous with diaphragmatic activity; IIC activity was occasionally present during expiration. Caudal intercostal muscle activity was more variable. These findings are in general agreement with previously published results in decerebrate (Fregosi and Baptlett 1989) and anaesthetized (Greer and Stein 1989; Greer and Martin 1998) cats. Similar results during coughing and vomiting were obtained in dB cats. Coughing was elicited in all cats and vomiting in six. An example of the EMG activities of different respiratory muscles during coughing is shown in Fig. 1. Coughing was characterized by an increased amplitude of diaphragmatic and EICg activity, both of which terminated transiently and then continued into the early part of the expiratory phase, concurrent with massive prolonged bursts of abdominal, IIC6, EICII, and IICBL activity. This persistence of activity is eonsistent with previous results in anaesthetized cats (Van Lunteren et al. 1989). During control respiratory cycles, activity was absent in rectus abdominis, EICI and IIC1,; EIC6 discharged in phase with the diaphragm whereas IIC6 discharged during expiration. (In Fig. 1, the activity in IICBB and EICla after the cough may be contamimation swing to increased activity from the subjacent diaphragm, as described by ]Be Troyer and Ninane (19861.)
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ABD
FIG. 2. Electrsmysgraphi activities from different muscles during vomiting. Traces are as described in Fig. 1, but recordings are from the 5th and 10th interspaces. The large spikes at bottom left are stimlus artifacts.
Vomiting (Fig. 2) consisted of, in this example, a series of six retches (the first six bursts of synchronous diaphragmatic, abdominal, and caudal intercostal activity) followed by a short diaphragmatic burst but prolonged bursts of abdominal and caudal intercostal activity. The discharge patterns during retching differed from those during coughing in two major ways: (i) the diaphragm, rectus abdominis, and caudal intercostal muscles were synchronously active, and (ii) midthoracic EHC and IIC discharged together but out of phase with the other muscles during retching. Some mid-thoracic EIC and %ICactivity, however, was synchronous with diaphragmatic activity, a result similar to that in an early report (Huleuhara et d. 1957). During the expulsion phase, the last cycle of activity, both mid-thoracic intercostal muscles started contracting during the second half of the discharges of the abdominal and caudal intercostals, but only after the cessation of phrenic activity. During control respiratory cycles (not shown), activity of the nondiaphragmatic muscles resembled that during control cycles in Fig. H except that mid-thoracic IIC activity was absent, and low levels of synchronous activity in the caudal intercostals, either in or out of phase with the diaphragm, were present. The timing of the onsets of diaphragmatic, abdominal, and caudal intercostal activity during retching varied within and between cats. En 5 of the 6 cats, the onset of diaphragmatic activity preceded that of the rectus abdominis and the caudal intercostal muscles. In 1 cat in which vomiting was elicited four times, diaphragmatic activity always preceded the activity of the other 6synchronously' active muscles but there was no consistent order of recruitment among them. In I cat, the onset of caudal intercostal activity preceded that of the diaphragm. Precise measurements of the delay between the onset of diaphragmatic activity and those s f the other muscles were difficult because of the presence of low levels of tonic EMG activity (not apparent in the figures at low recorder speed); delays typically ranged between 50 and 150 ms.
Discussion The major finding of this study is as follows: during coughing and vomiting, EIC and EIC at different levels had very different discharge patterns when referred to that of the diaphragm. This result generates two major conclusions. First, because EIC and EIC at one level can discharge in or out of phase with the same muscle at a different level during coughing or vomiting, intercostal muscles at different levels should be considered functionally distinct. Second, because of their dissimilar discharge patterns, the central pattern generators (CPGs) responsible for respiration, coughing, and vomiting exert precise and independent control over the discharges sf different intercostal muscles depending on their axial location. Classically, EIC are believed to elevate the ribs and IHC to lower them. Coactivation would therefore seem to be both ineffective and inefficient. However, function depends not only on which muscle (EIC or IIC) is activated but also on its cephalo-caudal location and on lung - rib cage volume (see koring and De Troyer 1985 for review). De Troyer et d. (1985) have shown, in anaesthetized dogs, that independent contraction of EIC or IIC of interspaces 3 -8 elevates the ribs at functional residual capacity (FWC); as lung - rib cage volume increases, this effect is converted to one En which contraction of either muscle lowers the ribs. Simultaneous contraction of EIC and IIIC produces similar effects. Ninane et al. (1991) have recently confirmed these results. Because we did not control lung volume in our cats, we do not know what effect coactivation of EIC and IIC would have had on rib cage configuration. Moreover, because our cats had open airways, they could not have generated the large transdiaphragmatic pressures typical of vomiting when the glottis is closed (McCarthy and Borison 1974). This large pressure gradient is necessary for retrograde motion sf the gastrointestinal contents. To prevent its dissipation by outward motion of the cau-
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dal rib cage, coactivation of the caudal intercostal muscles is necessary. Although the activation of mid-thoracic IIC between diaphragmatic bursts in our experiments agrees with the results of Hukuhara et al. (1957) and McCarthy and Borison (1974), the timing of mid-thoracic EIC activity does not. In McCarthy and Borison's study, mid-thoracic EIC activity was synchronous with diaphragmatic activity whereas in ours midthoracic EIC discharged together with IIC and between bursts of diaphragmatic activity. The reasons for this discrepancy are unclear; however, the EIC activity McCarthy and Borison recorded may have been pickup of underlying IIC activity. Such contamination is common in recordings of intercostal muscle activity from dogs during even modest respiratory efforts (De Troyer and Ninane 1986) and would be even more likely during the intense activation characteristic of vomiting. The EIC activity in our experiments was unlikely due to pickup of IIC activity because of the insulation placed between the two muscles. Contamination of IIC activity was also limited by removing the overlying EIC muscle and by denervating the adjacent interspaces. In addition, comparisons of EIC and IIC recordings from the same interspace always revealed instances in which one muscle was active when the other muscle was quiescent. Moreover, contamination cannot explain an absence of activity. e.g., the absence of EIC activity synchronous with that of the diaphragm. Lastly, coactivation of EHC and IIC was observed in all 6 cats that vomited. Consequently, we believe that the coactivation of mid-thoracic EIC and IIC was real. Segmental reflexes could also explain the presence of midthoracic EIC activity in phase with that of the diaphragm during vomiting (McCarthy and Borison 1974). Their cats were prone and suspended with their abdomens freely pendant; consequently, larger changes in abdominal configuration could have elicited greater reflex effects on intercostal activity than in our supine cats in whom abdominal motion may have been restricted. Second, and more importantly, in their experiments, cats could close the glottis during retching whereas in our cats, the airway remained open owing to the tracheostomy. Consequently, our cats could not have generated the large subatmospheric intrathoracic pressure swings observed in theirs. These negative pressure swings, by 'sucking in' an intact rib cage, could have elicited greater segmental reflex activation of intercostal muscles to prevent its collapse, thereby generating greater subatmospheric intrathoracic pressures. In addition, De Troyer (1991) has recently shown that rostral EIC are reflexly excited by activation of diaphragmatic afferents; this reflex, too, would have been weaker in our cats with open airways. Segmental reflexes may therefore be extremely important in modulating the discharge patterns of some intercostal muscles during vomiting. While our experimental conditions are not as 'natural' as those of McCarthy and Borison, the reduced pressure swings and, therefore, reduced distortion of the chest wall during retching may have resulted in less, or even no, reflex activation of EIC. Thus, the patterns of EMG activity of the different muscles recorded in our experiments likely better represent the output of the medullary vomiting centre(s). Although caudal EIC and IIC discharged in phase with the diaphragm and abdominal muscles during vomiting, only a third of ventral medullary expiratory neurones projecting to the lower thoracic (T13) or lumbar spinal cord fire synchronously with the diaphragm and abdominal muscles during vomiting (Miller et d. 1987). The discharge patterns of the
majority are, however, consistent with those of mid-thoracic EIC and IIC in this study, and with those of mid-thoracic IIC as described by McCarthy and Borison (1974). Expiratory medullary neurones discharging out of phase with the diaphragm and abdominal muscles may d s o project to inhibitory interneurones, a population of cells constituting as many as 50% of the neurones involved in motor control (Jankowska and Lundberg 1981; Mirkwood et a1. 1988). Medullary expiratory neurones firing in phase with the discharges of caudal intercostal muscles in our cats may project directly to the motoneurones. Interneurones may also exert substantial control over respiratory motoneurones at different spinal levels, thereby accounting for variations in intercostal muscle discharge patterns (Davies et d. 1985). The functional role of mid-thoracic intercostal muscle activation, both EIC and IIC, between diaphragmatic -abdominal coactivations is unclear. Because mid-thoracic IIC activity in anaesthetized dogs always occurs during the expiratory phase of the respiratory cycle (De Troyer m d Ninane 19861, the coactivation of EIC and IIC could, depending on thoracic rib cage volume (Ninane et al. 199I), increase the lengths, and improve the contractility, of the diaphragm and abdominal muscles during the subsequent contraction. The coactivation we observed, therefore, suggests a modification of the output from the respiratory CPG such that mid-thoracic EHC are coactivated with IIC. The influence of segmental reflexes on their activity cannot, however, be discounted. Different CPGs are likely responsible for these distinct behaviours even though the same 'respiratory' neurones and muscles are used. During vomiting, for example, medullary inspiratory premotor neurones of the dorsal respiratory group are inhibited (Bianchi and GrClot B989), yet the phrenic motoneurones to which they project remain active (Milano et al. 1992). Other premotor neurones, i.e., those of a still illdefined vomiting centre, must therefore be driving phrenic motoneurones. Although stimulation of many regions in the medulla can elicit vomiting behaviour, Fukuda and Koga (1991) recently claimed to have localized the vomiting centre to the area subpostrema, the output of which is channelled through neurones in the Botzinger complex, just caudal to the facial nucleus. This conclusion contradicts that of Miller and Wilson (1983), that the site of generation of emesis is distributed within the brainstem. Although neurones of the dorsal respiratory group are inhibited during vomiting (Bianchi and Grklot 1989), bulbospinal neurones of this region are also strongly activated during coughing (Grklot et al. 1991). Neurones of the ventral respiratory group in anaesthetized cats also increase their activity during cough and sneeze (JakuS et al. 1985). These workers found no evidence for activation of a separate pool of neurones subserving cough, a conclusion consistent with the inability of previous workers to localize the vomiting centre by means of electrical stimulation (Miller and Wilson 1983). Nevertheless, our observations that mid-thoracic intercostal muscles discharge in or out of phase with the diaphragm during vomiting and coughing, respectively (and that midthoracic EIC do both during coughing), suggest that distinct functional centres control the discharges of different respiratory muscles during these behaviours.
We thank Professor Yves Jammes for helpful suggestions, Drs. Federico Portillo and Armand Bianchi, and M. Stkphane
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Milano for their assistance. and Mrs. Sheila Gordon for preparing the figures. This research was supported by grants from the Medical Research Council of Canada, the Centre national de la recherche scientifique (Unit6 de recherche associ& 205; France), and la Direction des recherc.es, ktudes et techniques (961168). Bianchi, A. L., and GrClot, L. 1989. Converse motor output of inspiratory bulbospinal premotoneurones during vomiting. Neurosci. Lett. 104: 298 - 302. Bolser, D. 6. 1991. Fictive cough in the cat. J. Appl. Physiol. 71: 2325 -2331. Davies, J. G. McF., Kirkwood, P. A., and Sears, T. A. 1985. The distribution of monosynaptic connexions from inspiratory bulbospinal neurones to inspiratory motoneurones in the cat. J. Physiol. (London), 368: 63 - $7. De Troyer, A. 1991. Differential control of the inspiratory intercostal muscles during airway occlusion in the dog. J. Physiol. (London), 439: 73-88. De Troyer, A., and Ninane, V. 1986. Respiratory function of intercostal muscles in supine dog: an electromyographic study. J. Appl. Physiol. 60: 1692- 1699. De Troyer, A., Kelly, S., Macklem, P. T., and Zin, W. A. 1985. Mechanics of intercostal space and actions of external and internal intercostal muscles. J. Clin. Invest. 75: 850-857. Fregosi, R. F., and Bartlett, D., 9%.1989. Internal intercostal nerve discharges in the cat: influence of chemical stimuli. J. Appl. Physiol. 66: 687-694. F u h d a , H., and Koga, T. 1991. The Botzinger complex as the pattern generator for retching and vomiting in the dog. Neurosci. Res. 12: 471 -485. Greer, J. J., and Martin, T. P. 1990. Distribution of muscle fiber types and EMG activity in cat intercostal muscles. J. Appl. Physiol. 69: 1208- 1211. Greer, J. J., and Stein, R. B. 1989. Length changes of intercostal muscles during respiration in the cat. Respir. Physiol. 78: 309'lqq
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