{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:12:57Z","timestamp":1774620777868,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[1998,11,1]],"date-time":"1998-11-01T00:00:00Z","timestamp":909878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the effects of low-dose Beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on microvascular permeability and the plasma concentrations of thromboxane and adenosine 3 \u2032 ,5 \u2032 -cyclic monophosphate (cAMP) in blood-perfused rabbit lungs subjected to ischemia\u2013reperfusion (I\/R). After an ischemic insult for 2 h, saline as a vehicle, 3 pmol\/L of BPS (BPS-1), 150 to 300 pmol\/L of BPS (BPS-2), 900 pmol\/L of BPS (BPS-3), or 60 \u03bc mol\/L of indomethacin (IND) was administered into the reservoir, then the lungs were reperfused and reventilated for 1 h. Vascular permeability was assessed by determining the microvascular filtration coefficient (Kf, ml\/min\/mm Hg\/100 g wet lung). I\/R resulted in increases in vascular resistance, Kf, and thromboxane. BPS-2, BPS-3, and IND inhibited the increase in vascular resistance, and BPS-3 and IND attenuated the increases in Kf and thromboxane. BPS-3 increased, but IND decreased, the concentrations of cAMP in the perfusate. Perfusate thromboxane released after reperfusion was significantly correlated with Kf. We conclude that cyclooxygenase products play a critical role in I\/R-induced lung vascular injury and that 900 pmol\/L of BPS inhibits the production of thromboxane and enhances the permeability barrier via a cAMP-elevating effect. However, vasodilatory action of BPS may exacerbate the reperfused lung injury by increasing the flow through injured capillaries via inhibition of thromboxane-induced vasoconstriction.<\/jats:p>","DOI":"10.1164\/ajrccm.158.5.9609082","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:46:57Z","timestamp":1365083217000},"page":"1669-1675","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Low-Dose Beraprost Sodium, a Stable Prostaglandin I2 Analogue, on Reperfusion Injury to Rabbit Lungs"],"prefix":"10.1093","volume":"158","author":[{"given":"XIAO-WEN","family":"JIANG","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, Gifu University School of Medicine; and Hakuaikai General Hospital, Gifu, Japan"}]},{"given":"KENJIRO","family":"KAMBARA","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Gifu University School of Medicine; and Hakuaikai General Hospital, Gifu, Japan"}]},{"given":"NAOKI","family":"GOTOH","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Gifu University School of Medicine; and Hakuaikai General Hospital, Gifu, Japan"}]},{"given":"KAZUHIKO","family":"NISHIGAKI","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Gifu University School of Medicine; and Hakuaikai General Hospital, Gifu, Japan"}]},{"given":"HISAYOSHI","family":"FUJIWARA","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Gifu University School of Medicine; and Hakuaikai General Hospital, Gifu, Japan"}]}],"member":"286","published-online":{"date-parts":[[1998,11,1]]},"reference":[{"key":"2026032709073072400_B1","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1172\/JCI114019","article-title":"Role of reactive oxygen species in reperfusion injury of the rabbit lung.","volume":"83","author":"Kennedy","year":"1989","journal-title":"J. Clin. Invest."},{"key":"2026032709073072400_B2","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1152\/jappl.1990.69.6.2012","article-title":"Role of xanthine oxidase and neutrophils in ischemia\u2013reperfusion injury in rabbit lung.","volume":"69","author":"Adkins","year":"1990","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B3","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1172\/JCI114859","article-title":"Role of cytochrome p-450 in reperfusion injury of the rabbit lung.","volume":"86","author":"Bysani","year":"1990","journal-title":"J. Clin. Invest."},{"key":"2026032709073072400_B4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1164\/ajrccm\/147.2.270","article-title":"Ischemia\u2013reperfusion injury in the isolated rat lung; role of flow and endogenous leukocytes.","volume":"147","author":"Seibert","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B5","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1152\/jappl.1995.78.6.2245","article-title":"Adhesion molecules contribute to ischemia and reperfusion-induced injury in the isolated rat lung.","volume":"78","author":"Moore","year":"1995","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B6","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1152\/jappl.1994.77.2.774","article-title":"Reversal of pulmonary capillary ischemia\u2013reperfusion injury by rolipram, a cAMP phosphodiesterase inhibitor.","volume":"77","author":"Barnard","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B7","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1152\/jappl.1992.72.2.492","article-title":"Compounds that increase cAMP prevent ischemia\u2013reperfusion pulmonary capillary injury.","volume":"72","author":"Adkins","year":"1992","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B8","first-page":"L121","article-title":"Role of calmodulin and myosin light-chain kinase in lung ischemia\u2013 reperfusion injury.","volume":"271","author":"Khimenko","year":"1996","journal-title":"Am. J. Physiol."},{"key":"2026032709073072400_B9","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1152\/jappl.1991.71.4.1554","article-title":"Lung ischemia\u2013reperfusion injury in awake sheep: protection with verapamil.","volume":"71","author":"Wickersham","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B10","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1164\/ajrccm\/143.3.610","article-title":"Inhibition of cyclooxygenase metabolite production attenuates ischemia\u2013reperfusion lung injury.","volume":"143","author":"Ljungman","year":"1991","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B11","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1164\/ajrccm\/136.2.480","article-title":"The role of arachidonate mediators in peroxide-induced lung injury.","volume":"136","author":"Gurtner","year":"1987","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B12"},{"key":"2026032709073072400_B13","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1097\/00007890-199504000-00003","article-title":"Comparison of eurocollins and university of wisconsin solution in single flush preservation of the ischemic reperfused lung: an in vivo rabbit model.","volume":"59","author":"Balkhy","year":"1995","journal-title":"Transplantation"},{"key":"2026032709073072400_B14"},{"key":"2026032709073072400_B15","first-page":"H745","article-title":"Adverse effects of prostacyclin used to perfuse isolated lung lobes.","volume":"242","author":"Krausz","year":"1982","journal-title":"Am. J. Physiol."},{"key":"2026032709073072400_B16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1749-6632.1982.tb21372.x","article-title":"Pharmacology of prostaglandins in the pulmonary microcirculation.","volume":"384","author":"Ogletree","year":"1982","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2026032709073072400_B17","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1152\/jappl.1989.66.2.929","article-title":"Role of venoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs.","volume":"66","author":"Yoshimura","year":"1989","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B18","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1164\/ajrccm\/147.1.143","article-title":"Release of tumor necrosis factor after pulmonary artery occlusion and reperfusion.","volume":"147","author":"Palace","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B19","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/BF02514625","article-title":"Attentuation of ischemia reperfusion\u2013induced lung edema by prostaglandin I2 analogue OP-2507 in the isolated perfused rat lung.","volume":"8","author":"Okuda","year":"1994","journal-title":"J. Anesth."},{"key":"2026032709073072400_B20","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1097\/00007890-199006000-00001","article-title":"Amelioration of lung ischemic injury with prostacyclin.","volume":"49","author":"Hooper","year":"1990","journal-title":"Transplantation"},{"key":"2026032709073072400_B21","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1164\/ajrccm\/148.4_Pt_1.882","article-title":"Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1.","volume":"148","author":"Matsuzaki","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B22","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/00007890-199003000-00003","article-title":"The use of a prostacyclin analogue, Iloprost, as an adjunct to pulmonary preservation with eurocollins solution.","volume":"49","author":"Hooper","year":"1990","journal-title":"Transplantation"},{"key":"2026032709073072400_B23"},{"key":"2026032709073072400_B24","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/0006-2952(90)90053-N","article-title":"Prostacyclin and beraprost sodium as suppressors of activated rat polymorphonuclear leukocytes.","volume":"39","author":"Kainoh","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"2026032709073072400_B25","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1152\/jappl.1995.78.2.499","article-title":"Effect of blood and albumin on pulmonary hypertension and edema in perfused rabbit lungs.","volume":"78","author":"Kraft","year":"1995","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B26","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1152\/jappl.1986.60.2.464","article-title":"Low-dose PGI2 prevents monocrotaline-induced thromboxane production and lung injury.","volume":"60","author":"Czer","year":"1986","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B27","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1152\/jappl.1995.78.1.225","article-title":"Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats.","volume":"78","author":"Shen","year":"1995","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/jappl.1987.62.1.47","article-title":"Pharmacological modification of pulmonary vascular injury: possible role of cAMP.","volume":"62","author":"Farrukh","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B29","first-page":"256","article-title":"Isoproterenol or aminophylline attenuate pulmonary edema after acid lung injury.","volume":"131","author":"Mizus","year":"1985","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B30","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1152\/jappl.1986.60.1.266","article-title":"\u03b2-adrenergic modulation of pulmonary transvascular fluid and protein exchange.","volume":"60","author":"Minnear","year":"1986","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B31","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1152\/jappl.1987.63.6.2201","article-title":"Effects of dibutyryl cAMP on pulmonary air embolism-induced lung injury in awake sheep.","volume":"63","author":"Kobayashi","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"2026032709073072400_B32","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1164\/ajrccm\/140.6.1814","article-title":"Dibutyryl-cAMP blocks endotoxin-induced lung injury in rats.","volume":"140","author":"Chang","year":"1989","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0952-3278(95)90136-1","article-title":"Inhibition of beraprost sodium of thrombin-induced increase in endothelial macromolecular permeability.","volume":"53","author":"Imai-Sasaki","year":"1995","journal-title":"Prostagland. Leukotrienes Essent. Fatty Acids"},{"key":"2026032709073072400_B34","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1164\/ajrccm\/136.1.210","article-title":"Cyclic AMP-dependent regulation of lipid mediators in white cells.","volume":"136","author":"Kuehl","year":"1987","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709073072400_B35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF00500304","article-title":"Effects of PGI2 and PGI2 analogues on cAMP levels in cultured endothelial and smooth muscle cells derived from bovine arteries.","volume":"311","author":"Dembinska-Kiec","year":"1980","journal-title":"Naunyn-Schmiedeberg's Arch. Pharmacol."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/5\/1669\/67431599\/ajrccm_158_5_1669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/5\/1669\/67431599\/ajrccm_158_5_1669.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:07:56Z","timestamp":1774616876000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/158\/5\/1669\/8530244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,11,1]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1998,11,1]]},"published-print":{"date-parts":[[1998,11,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.158.5.9609082","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1998,11]]},"published":{"date-parts":[[1998,11,1]]}}}