{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:36:23Z","timestamp":1790163383968,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2008,10,30]],"date-time":"2008-10-30T00:00:00Z","timestamp":1225324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p>Sleep fragmentation (SF), a primary feature of obstructive sleep apnoea (OSA), impairs hippocampal long\u2010term potentiation and causes cognitive\/attention deficits. However, its influence upon respiratory control has hardly been studied. This study examined the effect of SF on ventilatory long\u2010term facilitation (LTF, a persistent augmentation of respiratory activity after episodic hypoxia) and the hypoxic ventilatory response (HVR), and investigated the role of adenosine A1 receptors in these SF effects in conscious adult male Sprague\u2013Dawley rats. SF, confirmed by sleep architecture recordings, was achieved by periodic, forced locomotion in a rotating drum (30 s rotation\/90 s stop for 24 h). LTF, elicited by five episodes of 5 min poikilocapnic hypoxia (10% O<jats:sub>2<\/jats:sub>) with 5 min intervals, was measured by plethysmography. Resting ventilation and metabolic rate were unchanged, HVR was reduced (150.6 \u00b1 3.5%<jats:italic>versus<\/jats:italic> 110.4 \u00b1 12.3%) and LTF was eliminated (22.6 \u00b1 0.5%<jats:italic>versus<\/jats:italic>\u22120.1 \u00b1 1.3%) shortly after 24 h SF. The SF\u2010induced impairments were SF duration dependent, and completely reversible as HVR (&lt; 24 h) and LTF (&lt; 48 h) returned spontaneously to their pre\u2010SF values. The SF\u2010impaired HVR was improved (130.3 \u00b1 4.2%) and SF\u2010eliminated LTF was restored (19.6 \u00b1 0.9%) by systemic injection of the adenosine A1 receptor antagonist 8\u2010CPT (2.5 mg kg<jats:sup>\u22121<\/jats:sup>) \u223c30 min before LTF elicitation. Both HVR and LTF were also similarly impaired by 24 h total sleep deprivation or 24 h repeated cage tapping\u2010induced SF, but not by a 24 h locomotion control protocol for SF. Collectively, these data suggest that: (1) 24 h SF impairs LTF and poikilocapnic HVR; (2) these impairments require A1 receptors; and (3) SF of OSA may exacerbate OSA <jats:italic>via<\/jats:italic> impaired ventilatory control mechanisms.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.158121","type":"journal-article","created":{"date-parts":[[2008,9,12]],"date-time":"2008-09-12T00:44:57Z","timestamp":1221180297000},"page":"5215-5229","source":"Crossref","is-referenced-by-count":22,"title":["Sleep fragmentation impairs ventilatory long\u2010term facilitation via adenosine A1 receptors"],"prefix":"10.1113","volume":"586","author":[{"given":"Michelle","family":"McGuire","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime L.","family":"Tartar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"McCarley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Strecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.6.2751"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15033.x"},{"key":"e_1_2_5_4_1","first-page":"709","article-title":"Long\u2010term facilitation of ventilation in humans during NREM sleep.","volume":"21","author":"Babcock MA","year":"1998","journal-title":"Sleep"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(96)00017-5"},{"key":"e_1_2_5_6_1","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1152\/jappl.1994.76.4.1682","article-title":"Effect of chemoreceptor stimulation and inhibition on total pulmonary resistance in humans during NREM sleep.","volume":"76","author":"Badr MS","year":"1994","journal-title":"J Appl Physiol"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1166"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90065-5"},{"key":"e_1_2_5_9_1","first-page":"1007","article-title":"Impairment of rat polymorphonuclear neutrophilic granulocyte phagocytosis following repeated hypobaric hypoxia.","volume":"61","author":"Bjerknes R","year":"1990","journal-title":"Aviat Space Environ Med"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305712101"},{"key":"e_1_2_5_11_1","first-page":"899","article-title":"Effect of sleep fragmentation on ventilatory and arousal responses of sleeping dogs to respiratory stimuli.","volume":"122","author":"Bowes G","year":"1980","journal-title":"Am Rev Respir Dis"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2005.04.001"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.88.2.1073"},{"key":"e_1_2_5_14_1","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1152\/jappl.1992.73.5.2083","article-title":"Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs.","volume":"73","author":"Cao K\u2010Y","year":"1992","journal-title":"J Appl Physiol"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2007.08.007"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1982.03320320033026"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(84)90364-9"},{"key":"e_1_2_5_18_1","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1523\/JNEUROSCI.15-05-03458.1995","article-title":"Modulation of inspiratory drive to phrenic motoneurons by presynaptic adenosine A1 receptors.","volume":"15","author":"Dong XW","year":"1995","journal-title":"J Neurosci"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-867080"},{"key":"e_1_2_5_20_1","first-page":"93","volume-title":"Handbook of Physiology, section 3, The Respiratory System, vol. 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