Muscimol dialysis in the rostral ventral medulla reduced the CO(2) response in awake and sleeping piglets.

Some victims of sudden infant death syndrome have arcuate nucleus abnormalities. The arcuate nucleus may be homologous with ventral medullary structures in the cat known to be involved in the control of breathing and the response to systemic hypercapnia. We refer to putative arcuate homologues in the piglet collectively as the rostral ventral medulla (RVM). We inhibited the RVM in awake and sleeping, chronically instrumented piglets by microdialysis of the GABA(A) receptor agonist muscimol. Muscimol dialysis (10 and 40 mM) had no effect on eupnea but caused a significant reduction in the response to hypercapnia during both wakefulness (34.8 +/- 8.7 and 30.7 +/- 10.1%, respectively) and sleep (36.7 +/- 6.7 and 49.5 +/- 8.9%, respectively). The effect of muscimol on the CO(2) response was entirely via a reduction in tidal volume and appeared to be greater during non-rapid-eye-movement sleep. We conclude that the piglet RVM contains neurons of importance in the response to systemic CO(2) during both wakefulness and non-rapid-eye-movement sleep. We hypothesize that dysfunction of homologous regions in the human infant could lead to impaired ability to respond to hypercapnia, particularly during sleep, which could potentially be involved in the pathogenesis of sudden infant death syndrome.

[1]  J C Smith,et al.  Brainstem projections to the major respiratory neuron populations in the medulla of the cat , 1989, The Journal of comparative neurology.

[2]  E. Nattie,et al.  Lesions in retrotrapezoid nucleus decrease ventilatory output in anesthetized or decerebrate cats. , 1991, Journal of applied physiology.

[3]  E. Nattie,et al.  Focal central chemoreceptor sensitivity in the RTN studied with a CO2 diffusion pipette in vivo. , 1997, Journal of applied physiology.

[4]  J. Severinghaus,et al.  Respiratory responses mediated through superficial chemosensitive areas on the medulla , 1963, Journal of applied physiology.

[5]  G. Hilaire,et al.  Noradrenergic modulation of the medullary respiratory rhythm generator in the newborn rat: an in vitro study. , 1991, The Journal of physiology.

[6]  John Kattwinkel,et al.  Changing Concepts of Sudden Infant Death Syndrome: Implications for Infant Sleeping Environment and Sleep Position , 2000, Pediatrics.

[7]  B. Thach.  How does prone sleeping increase prevalence of sudden infant death syndrome? , 1997, Pediatric pulmonology. Supplement.

[8]  J. Dempsey,et al.  Neural-mechanical coupling of breathing in REM sleep. , 1997, Journal of applied physiology.

[9]  H. Kinney,et al.  Decreased Kainate Receptor Binding in the Arcuate Nucleus of the Sudden Infant Death Syndrome , 1997, Journal of neuropathology and experimental neurology.

[10]  M. Fung,et al.  Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus to CO2. , 1993, Respiration physiology.

[11]  D. Henderson-smart,et al.  Ventilatory response of the sleeping newborn to CO2 during normoxic rebreathing. , 1991, Journal of applied physiology.

[12]  H. Ahmed,et al.  Optimized process for the fabrication of mesoscopic magnetic structures , 1997 .

[13]  H. Kinney,et al.  A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. , 1994, Biology of the neonate.

[14]  E. Nattie,et al.  Retrofacial lesions: effects on CO2-sensitive phrenic and sympathetic nerve activity. , 1992, Journal of applied physiology.

[15]  M. Schläfke,et al.  Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep. , 1998, Journal of applied physiology.

[16]  Task Force on Infant Sleep Position.  Changing concepts of SIDS : Implications for infant sleeping environment and sleep position , 2000 .

[17]  E. Nattie,et al.  Fluorescence location of RVLM kainate microinjections that alter the control of breathing. , 1990, Journal of applied physiology.

[18]  H. Kinney,et al.  Decreased Serotonergic Receptor Binding in Rhombic Lip‐Derived Regions of the Medulla Oblongata in the Sudden Infant Death Syndrome , 2000, Journal of neuropathology and experimental neurology.

[19]  G. Hilaire,et al.  Possible modulation of the medullary respiratory rhythm generator by the noradrenergic A5 area: an in vitro study in the newborn rat , 1989, Brain Research.

[20]  J. Mills,et al.  Kainic acid on the rostral ventrolateral medulla inhibits phrenic output and CO2 sensitivity. , 1988, Journal of applied physiology.

[21]  A. Basbaum,et al.  Medullary CO2 chemoreceptor neuron identification by c-fos immunocytochemistry. , 1992, Journal of applied physiology.

[22]  A. C. Bryan,et al.  Rib cage and abdominal contributions to ventilatory response to CO2 in infants. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[23]  E. Nattie,et al.  Central chemoreception in the region of the ventral respiratory group in the rat. , 1996, Journal of applied physiology.

[24]  R. Darnall,et al.  Lesion or muscimol in the rostral ventral medulla reduces ventilatory output and the CO(2) response in decerebrate piglets. , 2000, Respiration physiology.

[25]  R. Martin,et al.  Hypoglossal and phrenic responses to central respiratory inhibition in piglets. , 1994, Respiration physiology.

[26]  A. Dahan,et al.  Expression of c‐fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia , 1997, The Journal of comparative neurology.

[27]  J. Feldman,et al.  Respiratory activity in retrotrapezoid nucleus in cat. , 1990, The American journal of physiology.

[28]  B. Kalensher.  Blackbody radiation from cubes and spheres with application to rapid solidification of microspheres , 1984 .

[29]  H. Kinney,et al.  Candidate cell populations for respiratory chemosensitive fields in the human infant medulla , 1990, The Journal of comparative neurology.

[30]  H. Kinney,et al.  Arcuate Nucleus Hypoplasia in the Sudden Infant Death Syndrome , 1992, Journal of neuropathology and experimental neurology.

[31]  E. Murphy,et al.  Ventilatory and waking responses to CO2 in sleeping dogs. , 2015, The American review of respiratory disease.

[32]  Gengxin Chen,et al.  Potassium Permanganate Can Mark the Site of Microdialysis in Brain Sections , 2000 .

[33]  N. Cherniack,et al.  CO2-induced c-fos expression in the CNS catecholaminergic neurons. , 1996, Respiration physiology.

[34]  E. Nattie,et al.  Effects of unilateral lesions of retrotrapezoid nucleus on breathing in awake rats. , 1997, Journal of applied physiology.

[35]  J. Veening,et al.  Hypercapnia induces c-fos expression in neurons of retrotrapezoid nucleus in cats , 1994, Brain Research.

[36]  E. Nattie,et al.  Retrotrapezoid nucleus lesions decrease phrenic activity and CO2 sensitivity in rats. , 1994, Respiration physiology.

[37]  E. Nattie,et al.  CO(2) microdialysis in retrotrapezoid nucleus of the rat increases breathing in wakefulness but not in sleep. , 1999, Journal of applied physiology.

[38]  A. Netick,et al.  Ventilatory response to hypercapnia during sleep and wakefulness in cats. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[39]  G. Subramanyam,et al.  Fabrication and chemical composition of RF magnetron sputtered Tl-Ca-Ba-Cu-O high Tc superconducting thin films , 1990 .

[40]  E. Nattie,et al.  Widespread sites of brain stem ventilatory chemoreceptors. , 1993, Journal of applied physiology.

[41]  H. Kinney,et al.  Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome , 1995, Science.

[42]  R. A. Epstein,et al.  CO2-induced changes in ventilation and ventilatory pattern in normal sleeping infants. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[43]  The Central and Peripheral Nervous System , 1981 .