The carotid body in Sudden Infant Death Syndrome

Respiratory Physiology and Neurobiology

Volumn 185, Issue 1, 2013, Pages 194-201

  Porzionato, Andrea ^a   Macchi, Veronica ^a   Stecco, Carla ^a   De Caro, Raffaele ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

carotid body, Sudden Infant Death Syndrome, autonomic nervous system, nicotine, hypoxia, hyperoxia

Indexed keywords

ANIMAL; CAROTID BODY; HUMAN; NEWBORN; PATHOLOGY; PATHOPHYSIOLOGY; REVIEW; SUDDEN INFANT DEATH SYNDROME;

ANIMALS; CAROTID BODY; HUMANS; INFANT, NEWBORN; SUDDEN INFANT DEATH;

MLCS; MLOWN;

EID: 85027939570     PISSN: 15699048     EISSN: 18781519     Source Type: Journal    
DOI: 10.1016/j.resp.2012.05.013     Document Type: Review

References (102)

1. Aizad, T., Bodani, J., Cates, D., Horvath, L., Rigatto, H., Effect of a single breath of 100% oxygen on respiration in neonates during sleep. J. Appl. Physiol. 57 (1984), 1531–1535.
2. American Academy of Pediatrics, Hymel, K.P., Committee on Child Abuse and Neglect, National Association of Medical Examiners., 2006. Distinguishing sudden infant death syndrome from child abuse fatalities. Pediatrics 118, 421-427.
3. Baird, T.M., Clinical correlates. natural history and outcome of neonatal apnoea. Semin. Neonatol. 9 (2004), 205–211.
4. Bamford, O.S., Carroll, J.L., Dynamic ventilatory responses in rats: normal development and effects of prenatal nicotine exposure. Respir. Physiol 117 (1999), 29–40.
5. Bavis, R.W., Wenninger, J.M., Miller, B.M., Dmitrieff, E.F., Olson E.B.Jr. Mitchell, G.S., Bisgard, G.E., Respiratory plasticity after perinatal hyperoxia is not prevented by antioxidant supplementation. Respir. Physiol. Neurobiol. 160 (2008), 301–312.
6. Berner, J., Ringstedt, T., Brodin, E., Hökfelt, T., Lagercrantz, H., Wickström, R., Prenatal exposure to nicotine affects substance p and preprotachykinin-A mRNA levels in newborn rat. Pediatr. Res 64 (2008), 621–624.
7. Bisgard, G.E., Olson E.B.Jr. Wang, Z.Y., Bavis, R.W., Fuller, D.D., Mitchell, G.S., Adult carotid chemoafferent responses to hypoxia after 1, 2, and 4 wk of postnatal hyperoxia. J. Appl. Physiol. 95 (2003), 946–952.
8. Blair, P.S., Platt, M.W., Smith, I.J., Fleming, P.J., CESDI SUDI Research Group. Sudden infant death syndrome and sleeping position in pre-term and low birth weight infants: an opportunity for targeted intervention. Arch. Dis. Child. 91 (2006), 101–106.
9. Bowes, G., Townsend, E.R., Kozar, L.F., Bromley, S.M., Phillipson, E.A., Effect of carotid body denervation on arousal response to hypoxia in sleeping dogs. J. Appl. Physiol. 51 (1981), 40–45.
10. Bowes, G., Townsend, E.R., Bromley, S.M., Kozar, L.F., Phillipson, E.A., Role of the carotid body and of afferent vagal stimuli in the arousal response to airway occlusion in sleeping dogs. Am. Rev. Respir. Dis. 123 (1981), 644–647.
11. Broadbelt, K.G., Paterson, D.S., Belliveau, R.A., Trachtenberg, F.L., Haas, E.A., Stanley, C., Krous, H.F., Kinney, H.C., Decreased GABAA receptor binding in the medullary serotonergic system in the sudden infant death syndrome. J. Neuropathol. Exp. Neurol. 70 (2011), 799–810.
12. Broadbelt, K.G., Rivera, K.D., Paterson, D.S., Duncan, J.R., Trachtenberg, F.L., Paulo, J.A., Stapels, M.D., Borenstein, N.S., Belliveau, R.A., Haas, E.A., Stanley, C., Krous, H.F., Steen, H., Kinney, H.C., 2012. Brainstem deficiency of the 14-3-3 regulator of serotonin synthesis: a proteomics analysis in the sudden infant death syndrome. Mol. Cell. Proteomics. 11, M111.009530.
13. Bureau, M.A., Lamarche, J., Foulon, P., Dalle, D., The ventilatory response to hypoxia in the newborn lamb after carotid body denervation. Respir. Physiol. 60 (1985), 109–119.
14. Buttigieg, J., Brown, S., Holloway, A.C., Nurse, C.A., Chronic nicotine blunts hypoxic sensitivity in perinatal rat adrenal chromaffin cells via upregulation of KATP channels: role of alpha7 nicotinic acetylcholine receptor and hypoxia-inducible factor-2alpha. J. Neurosci. 29 (2009), 7137–7147.
15. Calder, N.A., Williams, B.A., Smyth, J., Boon, A.W., Kumar, P., Hanson, M.A., Absence of ventilatory responses to alternating breaths of mild hypoxia and air in infants who have had bronchopulmonary dysplasia: implications for the risk of sudden infant death. Pediatr. Res 35 (1994), 677–681.
16. Carley, D.W., Paviovic, S., Janelidze, M., Radulovacki, M., Functional role for cannabinoids in respiratory stability during sleep. Sleep 25 (2002), 391–398.
17. Carroll, J.L., Kim, I., Dbouk, H., Yang, D.J., Bavis, R.W., Donnelly, D.F., Time-dependence of hyperoxia-induced impairment in peripheral chemoreceptor activity and glomus cell calcium response. Adv. Exp. Med. Biol 648 (2009), 299–306.
18. Chang, K.C., Morrill, C.G., Chai, H., Impaired response to hypoxia after bilateral carotid body resection for treatment of bronchial asthma. Chest 73 (1978), 667–669.
19. Cole, S., Lindenberg, L.B., Galioto F.M.Jr. Howe, P.E., DeGraff A.C.Jr. Davis, J.M., Lubka, R., Gross, E.M., Ultrastructural abnormalities of the carotid body in sudden infant death syndrome. Pediatrics 63 (1979), 13–17.
20. Côté, A., Porras, H., Meehan, B., Age-dependent vulnerability to carotid chemodenervation in piglets. J. Appl. Physiol. 80 (1996), 323–331.
21. Cutz, E., Ma, T.K., Perrin, D.G., Moore, A.M., Becker, L.E., Peripheral chemoreceptors in congenital central hypoventilation syndrome. Am. J. Respir. Crit. Care Med. 155 (1997), 358–363.
22. Di Giulio, C., Di Muzio, M., Sabatino, G., Spoletini, L., Amicarelli, F., Di Ilio, C., Modesti, A., Effect of chronic hyperoxia on young and old rat carotid body ultrastructure. Exp. Gerontol. 33 (1998), 319–329.
23. Dinsdale, F., Emery, J.L., Gadsdon, D.R., The carotid body–a quantitative assessment in children. Histopathology 1 (1977), 179–187.
24. Dmitrieff, E.F., Wilson, J.T., Dunmire, K.B., Bavis, R.W., Chronic hyperoxia alters the expression of neurotrophic factors in the carotid body of neonatal rats. Respir. Physiol. Neurobiol. 175 (2011), 220–227.
25. Donnelly, D.F., Haddad, G.G., Prolonged apnea and impaired survival in piglets after sinus and aortic nerve section. J. Appl. Physiol. 68 (1990), 1048–1052.
26. Donnelly, D.F., Kim, I., Carle, C., Carroll, J.L., Perinatal hyperoxia for 14 days increases nerve conduction time and the acute unitary response to hypoxia of rat carotid body chemoreceptor. J. Appl. Physiol 99 (2005), 114–119.
27. Eden, G.J., Hanson, M.A., Effects of chronic hypoxia from birth on the ventilatory response to acute hypoxia in the newborn rat. J. Physiol. 392 (1987), 11–19.
28. Erickson, J.T., Mayer, C., Jawa, A., Ling, L., Olson E.B.Jr. Vidruk, E.H., Mitchell, G.S., Katz, D.M., Chemoafferent degeneration and carotid body hypoplasia following chronic hyperoxia in newborn rats. J. Physiol. 509 (1998), 519–526.
29. Fewell, J.E., Kondo, C.S., Dascalu, V., Filyk, S.C., Influence of carotid denervation on the arousal and cardiopulmonary response to rapidly developing hypoxemia in lambs. Pediatr. Res. 25 (1989), 473–477.
30. Fewell, J.E., Kondo, C.S., Dascalu, V., Filyk, S.C., Influence of carotid-denervation on the arousal and cardiopulmonary responses to alveolar hypercapnia in lambs. J. Dev. Physiol. 12 (1989), 193–199.
31. Fewell, J.E., Taylor, B.J., Kondo, C.S., Dascalu, V., Filyk, S.C., Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs. Pediatr. Res. 28 (1990), 374–378.
32. Fewell, J.E., Smith, F.G., Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia. J. Appl. Physiol. 85 (1998), 2066–2074.
33. Filiano, J.J., Kinney, H.C., A perspective on neuropathologic findings in victims of sudden infant death syndrome: the triple risk model. Biol. Neonate 65 (1994), 194–197.
34. Franco, P., Kato, I., Richardson, H.L., Yang, J.S., Montemitro, E., Horne, R.S., Arousal from sleep mechanisms in infants. Sleep Med. 11 (2010), 603–614.
35. Gauda, E.B., Cooper, R., Akins, P.K., Wu, G., Prenatal nicotine affects catecholamine gene expression in newborn rat carotid body and petrosal ganglion. J. Appl. Physiol. 91 (2001), 2157–2165.
36. Gauda, E.B., McLemore, G.L., Tolosa, J., Marston-Nelson, J., Kwak, D., Maturation of peripheral arterial chemoreceptors in relation to neonatal apnoea. Semin. Neonatol. 9 (2004), 181–194.
37. Gauda, E.B., Cristofalo, E., Nunez, J., Peripheral arterial chemoreceptors and sudden infant death syndrome. Respir. Physiol. Neurobiol 157 (2007), 162–170.
38. Gaultier, C., Development of the control of breathing: implications for sleep-related breathing disorders in infants. Sleep 23 (2000), S136–S139.
39. Grogaard, J., Kreuger, E., Lindstrom, D., Sundell, H., Effects of carotid body maturation and terbutaline on the laryngeal chemoreflex in newborn lambs. Pediatr. Res. 20 (1986), 724–729.
40. Hafstrom, O., Milerad, J., Sundell, H.W., Prenatal nicotine exposure blunts the cardiorespiratory response to hypoxia in lambs. Am. J. Respir. Crit. Care Med. 166 (2002), 1544–1549.
41. Hagadorn, J.I., Furey, A.M., Nghiem, T.H., Schmid, C.H., Phelps, D.L., Pillers, D.A., Cole, C.H., AVIOx Study Group., 2006. Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks’ gestation: the AVIOx study. Pediatrics 118, 1574-1582.
42. Hasan, S.U., Yusuf, K., 2012. Rat homologues to the human post neonatal period: Models for vulnerability to the Sudden infant death syndrome. Pediatr. Pulmonol. In press.
43. Heath, D., Khan, Q., Smith, P., Histopathology of the carotid bodies in neonates and infants. Histopathology 17 (1990), 511–519.
44. Hofer, M.A., Role of carotid sinus and aortic nerves in respiratory control of infant rats. Am. J. Physiol. 251 (1986), R811–R817.
45. Holgert, H., Hokfelt, T., Hertzberg, T., Lagercrantz, H., Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Proc. Natl. Acad. Sci. USA 92 (1995), 7575–7579.
46. Hutter, C.D., Blair, M.E., Carbon monoxide-does fetal exposure cause sudden infant death syndrome? Med. Hypotheses 46 (1996), 1–4.
47. Julien, C., Bairam, A., Joseph, V., Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats. Am. J. Physiol. Regul. Integr. Comp. Physiol 294 (2008), R1356–R1366.
48. Julien, C.A., Niane, L., Kinkead, R., Bairam, A., Joseph, V., Carotid sinus nerve stimulation but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299 (2010), R192–R205.
49. Kandall, S.R., Gaines, J., Habel, L., Davidson, G., Jessop, D., Relationship of maternal substance abuse to subsequent sudden infant death syndrome in offspring. J. Pediatr. 123 (1993), 120–126.
50. Kahn, A., Groswasser, J., Rebuffat, E., Sottiaux, M., Blum, D., Foerster, M., Franco, P., Bochner, A., Alexander, M., Bachy, A., Sleep and cardiorespiratory characteristics of infant victims of sudden death: a prospective case-control study. Sleep 15 (1992), 287–292.
51. Kahn, A., Groswasser, J., Franco, P., Scaillet, S., Sawaguchi, T., Kelmanson, I., Dan, B., 2003. Sudden infant deaths: stress, arousal and SIDS. Early Hum. Dev. 75 Suppl, S147-166.
52. 2 apneic threshold in newborn infants: possible relevance for periodic breathing and apnea. J. Appl. Physiol. 98 (2005), 1171–1176.
53. Kinney, H.C., Thach, B.T., The sudden infant death syndrome. N. Engl. J. Med 361 (2009), 795–805.
54. Krous, H.F., Beckwith, J.B., Byard, R.W., Rognum, T.O., Bajanowski, T., Corey, T., Cutz, E., Hanzlick, R., Keens, T.G., Mitchell, E.A., Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 114 (2004), 234–238.
55. Lack, E.E., Perez-Atayde, A.R., Young, J.B., Carotid bodies in sudden infant death syndrome: a combined light microscopic. ultrastructural, and biochemical study. Pediatr. Pathol. 6 (1986), 335–350.
56. 2 chemoreception in the cat carotid body. Respir. Physiol 94 (1993), 227–240.
57. Laptook, A.R., Salhab, W., Allen, J., Saha, S., Walsh, M., Pulse oximetry in very low birth weight infants: can oxygen saturation be maintained in the desired range? J. Perinatol 26 (2006), 337–341.
58. Lewis, K.W., Bosque, E.M., Deficient hypoxia awakening response in infants of smoking mothers: possible relationship to sudden infant death syndrome. J. Pediatr. 127 (1995), 691–699.
59. Ling, L., Olson E.B.Jr. Vidruk, E.H., Mitchell, G.S., Integrated phrenic responses to carotid afferent stimulation in adult rats following perinatal hyperoxia. J. Physiol. 500 (1997), 787–796.
60. Lipton, J.W., Yuengsrigul, A., Ling, Z.D., Weese-Mayer, D.E., Carvey, P.M., Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats. Neurotoxicol. Teratol. 18 (1996), 283–287.
61. Lipton, J.W., Ling, Z., Vu, T.Q., Robie, H.C., Mangan, K.P., Weese-Mayer, D.E., Carvey, P.M., Prenatal cocaine exposure reduces glial cell line-derived neurotrophic factor (GDNF) in the striatum and the carotid body of the rat: implications for DA neurodevelopment. Brain Res. Dev. Brain Res 118 (1999), 231–235.
62. Machaalani, R., Say, M., Waters, K.A., Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits α7 and β2 in the sudden infant death syndrome (SIDS) brainstem. Toxicol. Appl. Pharmacol 257 (2011), 396–404.
63. Matturri, L., Migliarini, A.M., Rossi, L., Changes in the cardiovascular chemo-baroreceptors as a possible basis for sudden infant death syndrome (SIDS). Pathologica 84 (1992), 467–471.
64. McGregor, H.P., Westcott, K., Walker, D.W., The effect of prenatal exposure to carbon monoxide on breathing and growth of the newborn guinea pig. Pediatr. Res. 43 (1998), 126–131.
65. McLemore, G.L., Cooper, R.Z., Richardson, K.A., Mason, A.V., Marshall, C., Northington, F.J., Gauda, E.B., Cannabinoid receptor expression in peripheral arterial chemoreceptors during postnatal development. J. Appl. Physiol. 97 (2004), 1486–1495.
66. McQueen, D.S., Ribeiro, J.A., Inhibitory actions of methionine-enkephalin and morphine on the cat carotid chemoreceptors. Br. J. Pharmacol 71 (1980), 297–305.
67. Miller, M.J., Tenney, S.M., Hypoxia-induced tachypnea in carotid-deafferented cats. Respir. Physiol 23 (1975), 31–39.
68. Naeye, R.L., Fisher, R., Ryser, M., Whalen, P., Carotid body in the sudden infant death syndrome. Science 191 (1976), 567–569.
69. Nock, M.L., Difiore, J.M., Arko, M.K., Martin, R.J., Relationship of the ventilatory response to hypoxia with neonatal apnea in preterm infants. J. Pediatr. 144 (2004), 291–295.
70. Paterson, D.S., Hilaire, G., Weese-Mayer, D.E., Medullary serotonin defects and respiratory dysfunction in sudden infant death syndrome. Respir. Physiol. Neurobiol. 168 (2009), 133–143.
71. Pavai, Z., Toro, K., Keller, E., Jung, J., Morphometric investigation of carotid body in sudden infant death syndrome. Rom. J. Morphol. Embryol. 46 (2005), 93–97.
72. Peng, Y.J., Rennison, J., Prabhakar, N.R., Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in neonatal rat pups. J. Appl. Physiol 97 (2004), 2020–2025.
73. Perrin, D.G., Cutz, E., Becker, L.E., Bryan, A.C., Ultrastructure of carotid bodies in sudden infant death syndrome. Pediatrics 73 (1984), 646–651.
74. Perrin, D.G., Cutz, E., Becker, L.E., Bryan, A.C., Madapallimatum, A., Sole, M.J., Sudden infant death syndrome: increased carotid-body dopamine and noradrenaline content. Lancet 2 (1984), 535–537.
75. Porzionato, A., Macchi, V., Guidolin, D., Parenti, A., Ferrara, S.D., De Caro, R., Histopathology of carotid body in heroin addiction. Possible chemosensitive impairment. Histopathology 46 (2005), 296–306.
76. Porzionato, A., Macchi, V., Parenti, A., Matturri, L., De Caro, R., Peripheral chemoreceptors: postnatal development and cytochemical findings in Sudden Infant Death Syndrome. Histol. Histopathol 23 (2008), 351–365.
77. Porzionato, A., Macchi, V., Parenti, A., De Caro, R., Trophic factors in the carotid body. Int. Rev. Cell. Mol. Biol. 269 (2008), 1–58.
78. Porzionato, A., Macchi, V., De Caro, R., Sudden infant death syndrome. N. Engl. J. Med, 361, 2009, 2580.
79. Porzionato, A., Rucinski, M., Macchi, V., Stecco, C., Sarasin, G., Sfriso, M.M., Di Giulio, C., Malendowicz, L.K., De Caro, R., 2012. Spexin is expressed in the carotid body and is upregulated by postnatal hyperoxia exposure. Adv. Exp. Med. Biol. In press.
80. Prabhakar, N.R., Peng, Y.J., Kumar, G.K., Pawar, A., Altered carotid body function by intermittent hypoxia in neonates and adults: relevance to recurrent apneas. Respir. Physiol. Neurobiol 157 (2007), 148–153.
81. Prabhakar, N.R., Semenza, G.L., Gaseous messengers in oxygen sensing. J. Mol. Med 90 (2012), 265–272.
82. Quinn, R., Comparing rat‘s to human‘s age: how old is my rat in people years?. Nutrition 21 (2005), 775–777.
83. Riesco-Fagundo, A.M., Pérez-García, M.T., González, C., López-López, J.R., O(2) modulates large-conductance Ca(2 + )-dependent K(+) channels of rat chemoreceptor cells by a membrane-restricted and CO-sensitive mechanism. Circ. Res 89 (2001), 430–436.
84. Robinson, D.M., Peebles, K.C., Kwok, H., Adams, B.M., Clarke, L.L., Woollard, G.A., Funk, G.D., Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice. J. Physiol. 538 (2002), 957–973.
85. Scragg, R.K., Mitchell, E.A., Ford, R.P., Thompson, J.M., Taylor, B.J., Stewart, A.W., Maternal cannabis use in the sudden death syndrome. Acta Paediatr. 90 (2001), 57–60.
86. Seker, M., Pallot, D.J., Habeck, J.O., Abramovici, A., Postmortem changes in the human carotid body. Adv. Exp. Med. Biol. 360 (1994), 349–351.
87. Sladek, M., Parker, R.A., Grŏgaard, J.B., Sundell, H.W., Long-lasting effect of prolonged hypoxemia after birth on the immediate ventilatory response to changes in arterial partial pressure of oxygen in young lambs. Pediatr. Res 34 (1993), 821–828.
88. Slotkin, T.A., Lappi, S.E., McCook, E.C., Lorber, B.A., Seidler, F.J., Loss of neonatal hypoxia tolerance after prenatal nicotine exposure: implications for sudden infant death syndrome. Brain Res. Bull 38 (1995), 69–75.
89. Smith, C.A., Forster, H.V., Blain, G.M., Dempsey, J.A., An interdependent model of central/peripheral chemoreception: evidence and implications for ventilatory control. Respir. Physiol. Neurobiol 173 (2010), 288–297.
90. Sola, A., Saldeño, Y.P., Favareto, V., Clinical practices in neonatal oxygenation: where have we failed?. What can we do? J. Perinatol. 28 Suppl 1 (2008), S28–S34.
91. Sterni, L.M., Bamford, O.S., Wasicko, M.J., Carroll, J.L., Chronic hypoxia abolished the postnatal increase in carotid body type I cell sensitivity to hypoxia. Am. J. Physiol. 277 (1999), L645–L652.
92. St-John, W.M., Leiter, J.C., Maternal nicotine depresses eupneic ventilation of neonatal rats. Neurosci. Lett. 267 (1999), 206–208.
93. Sullivan, C.E., Bilateral carotid body resection in asthma: vulnerability to hypoxic death in sleep. Chest, 78, 1980, 354.
94. Tang, S., Machaalani, R., Waters, K.A., Expression of brain-derived neurotrophic factor and TrkB receptor in the sudden infant death syndrome brainstem. Respir. Physiol. Neurobiol 180 (2012), 25–33.
95. Tolcos, M., McGregor, H., Walker, D., Rees, S., Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome. J. Neuropathol. Exp. Neurol. 59 (2000), 218–228.
96. Tong, E.K., England, L., Glantz, S.A., Changing conclusions on secondhand smoke in a sudden infant death syndrome review funded by the tobacco industry. Pediatrics 115 (2005), 356–366.
97. Ueda, Y., Stick, S.M., Hall, G., Sly, P.D., Control of breathing in infants born to smoking mothers. J. Pediatr. 135 (1999), 226–232.
98. Valdés-Dapena, M.A., 1980. Sudden infant death syndrome: a review of the medical literature 1974-1979. Pediatrics 66, 597-614.
99. Ward, S.L., Bautista, D., Chan, L., Derry, M., Lisbin, A., Durfee, M.J., Mills, K.S., Keens, T.G., Sudden infant death syndrome in infants of substance-abusing mothers. J. Pediatr. 117 (1990), 876–881.
100. Waters, K.A., Tinworth, K.D., Depression of ventilatory responses after daily, cyclic hypercapnic hypoxia in piglets. J. Appl. Physiol. 90 (2001), 1065–1073.
101. Willinger, M., James, L.S., Catz, C., Defining the Sudden Infant Death Syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health Development. Pediatric Pathol 11 (1991), 677–684.
102. Zhuang, J., Xu, F., Campen, M., Hernandez, J., Shi, S., Wang, R., Transient carbon monoxide inhibits the ventilatory responses to hypoxia through peripheral mechanisms in the rat. Life Sci 78 (2006), 2654–2661.