{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:13:44Z","timestamp":1773332024985,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inhaled nitric oxide (iNO) is a commonly used pulmonary vasodilator in neonates, but its effects on intestinal perfusion remain unclear. This study assessed the impact of iNO on splanchnic tissue oxygenation as a surrogate for intestinal perfusion using near infrared spectroscopy (NIRS), with NG-nitro-L-arginine methyl ester (L-NAME) used to inhibit endogenous nitric oxide synthase (NOS) and isolate the effect of exogenous NO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventeen piglets (7\u201310 days old) were anesthetized and ventilated with NIRS probes placed on the forehead and abdomen. Piglets were allocated to group 1 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) receiving iNO only, group 2 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) receiving iNO then L-NAME, and group 3 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097) receiving L-NAME then iNO. Serum nitrate\/nitrite and endothelin-1 expression were assessed via colorimetric assay and ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      iNO increased splanchnic oxygenation, significantly reducing the difference between cerebral and abdominal NIRS. This effect was blunted by L-NAME pre-treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02 at 0 and 60\u2009ppm). Serum nitrate\/nitrite and endothelin-1 levels did not differ significantly between groups, nor did mean arterial pressure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>iNO enhances splanchnic tissue oxygenation to near cerebral levels. Pretreatment with L-NAME eliminates this effect, suggesting a role for endogenous NOS in this process. These findings suggest a potential protective role of iNO against intestinal ischemia and merit further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>As shown in previous studies, there are extrapulmonary effects of inhaled nitric oxide (iNO) on tissue perfusion; this study specifically validates this by evaluating oxygenation of the gut.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>iNO increases splanchnic tissue oxygenation to cerebral levels.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This preclinical research establishes improvement in intestinal oxygenation with iNO use in contrast to other studies proposing iNO as a potential contributor to the development of NEC in the setting of cardiac defects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This study suggests that iNO could be a potential therapeutic agent in ischemic intestinal conditions.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-04895-8","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:53:29Z","timestamp":1773287609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of inhaled nitric oxide on splanchnic perfusion in a neonatal piglet model"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7120-4324","authenticated-orcid":false,"given":"Sophia G.","family":"Hameedi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica G.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6138-944X","authenticated-orcid":false,"given":"Meghan E.","family":"Hovell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carly G.","family":"Schafer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Kamr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-6345","authenticated-orcid":false,"given":"Louren\u00e7o","family":"Sbragia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1619-3970","authenticated-orcid":false,"given":"Oluyinka O.","family":"Olutoye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"4895_CR1","doi-asserted-by":"publisher","first-page":"S159","DOI":"10.33549\/physiolres.933673","volume":"66","author":"M Antosova","year":"2017","unstructured":"Antosova, M. et al. Physiology of nitric oxide in the respiratory system. Physiol. Res 66, S159\u2013s172 (2017).","journal-title":"Physiol. Res"},{"key":"4895_CR2","doi-asserted-by":"publisher","first-page":"2853","DOI":"10.1016\/j.cell.2022.06.010","volume":"185","author":"JO Lundberg","year":"2022","unstructured":"Lundberg, J. O. & Weitzberg, E. Nitric oxide signaling in health and disease. Cell 185, 2853\u20132878 (2022).","journal-title":"Cell"},{"key":"4895_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.clp.2023.11.001","volume":"51","author":"MW Cookson","year":"2024","unstructured":"Cookson, M. W. & Kinsella, J. P. Inhaled nitric oxide in neonatal pulmonary hypertension. Clin. Perinatol. 51, 95\u2013111 (2024).","journal-title":"Clin. Perinatol."},{"key":"4895_CR4","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1172\/JCI2736","volume":"101","author":"A Fox-Robichaud","year":"1998","unstructured":"Fox-Robichaud, A. et al. Inhaled No as a viable antiadhesive therapy for ischemia\/reperfusion injury of distal microvascular beds. J. Clin. Investig. 101, 2497\u20132505 (1998).","journal-title":"J. Clin. Investig."},{"key":"4895_CR5","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1513\/pats.200507-066BG","volume":"3","author":"TJ McMahon","year":"2006","unstructured":"McMahon, T. J. & Doctor, A. Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin. Proc. Am. Thorac. Soc. 3, 153\u2013160 (2006).","journal-title":"Proc. Am. Thorac. Soc."},{"key":"4895_CR6","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1161\/01.RES.0000117771.63140.D6","volume":"94","author":"ES Ng","year":"2004","unstructured":"Ng, E. S. et al. Enhanced S-nitroso-albumin formation from inhaled no during ischemia\/reperfusion. Circ. Res. 94, 559\u2013565 (2004).","journal-title":"Circ. Res."},{"key":"4895_CR7","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1097\/MPG.0000000000000523","volume":"59","author":"KW Reisinger","year":"2014","unstructured":"Reisinger, K. W. et al. Breast-feeding improves gut maturation compared with formula feeding in preterm babies. J. Pediatr. Gastroenterol. Nutr. 59, 720\u2013724 (2014).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"4895_CR8","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1161\/CIRCULATIONAHA.111.025395","volume":"124","author":"S Minamishima","year":"2011","unstructured":"Minamishima, S. et al. Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice. Circulation 124, 1645\u20131653 (2011).","journal-title":"Circulation"},{"key":"4895_CR9","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.niox.2021.07.001","volume":"115","author":"JK Patel","year":"2021","unstructured":"Patel, J. K. et al. Inhaled nitric oxide in adults with in-hospital cardiac arrest: a feasibility study. Nitric Oxide 115, 30\u201333 (2021).","journal-title":"Nitric Oxide"},{"key":"4895_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-022-00455-6","volume":"10","author":"D Signori","year":"2022","unstructured":"Signori, D. et al. Inhaled nitric oxide: role in the pathophysiology of cardio-cerebrovascular and respiratory diseases. Intensive Care Med Exp. 10, 28 (2022).","journal-title":"Intensive Care Med Exp."},{"key":"4895_CR11","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1093\/bja\/79.5.631","volume":"79","author":"E Troncy","year":"1997","unstructured":"Troncy, E. et al. Extra-pulmonary effects of inhaled nitric oxide in swine with and without phenylephrine. Br. J. Anaesth. 79, 631\u2013640 (1997).","journal-title":"Br. J. Anaesth."},{"key":"4895_CR12","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1164\/rccm.201710-2150OC","volume":"198","author":"C Lei","year":"2018","unstructured":"Lei, C. et al. Nitric oxide decreases acute kidney injury and stage 3 chronic kidney disease after cardiac surgery. Am. J. Respir. Crit. Care Med 198, 1279\u20131287 (2018).","journal-title":"Am. J. Respir. Crit. Care Med"},{"key":"4895_CR13","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1097\/00003246-200004000-00027","volume":"28","author":"R Nevi\u00e8re","year":"2000","unstructured":"Nevi\u00e8re, R. et al. Inhaled nitric oxide modulates leukocyte kinetics in the mesenteric venules of endotoxemic rats. Crit. Care Med. 28, 1072\u20131076 (2000).","journal-title":"Crit. Care Med."},{"key":"4895_CR14","first-page":"L1224","volume":"277","author":"A Fox-Robichaud","year":"1999","unstructured":"Fox-Robichaud, A., Payne, D. & Kubes, P. Inhaled No reaches distal vasculatures to inhibit endothelium- but not leukocyte-dependent cell adhesion. Am. J. Physiol. 277, L1224\u2013L1231 (1999).","journal-title":"Am. J. Physiol."},{"key":"4895_CR15","first-page":"H676","volume":"277","author":"P Kubes","year":"1999","unstructured":"Kubes, P., Payne, D., Grisham, M. B., Jourd-Heuil, D. & Fox-Robichaud, A. Inhaled no impacts vascular but not extravascular compartments in postischemic peripheral organs. Am. J. Physiol. 277, H676\u2013H682 (1999).","journal-title":"Am. J. Physiol."},{"key":"4895_CR16","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.jss.2023.02.020","volume":"288","author":"AD Menchaca","year":"2023","unstructured":"Menchaca, A. D. et al. Inhaled nitric oxide and higher necrotizing enterocolitis rates in congenital heart disease patients. J. Surg. Res. 288, 166\u2013171 (2023).","journal-title":"J. Surg. Res."},{"key":"4895_CR17","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.jpedsurg.2011.03.025","volume":"46","author":"AN Gay","year":"2011","unstructured":"Gay, A. N. et al. Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets. J. Pediatr. Surg. 46, 1034\u20131040 (2011).","journal-title":"J. Pediatr. Surg."},{"key":"4895_CR18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1097\/00004872-200401000-00026","volume":"22","author":"O Pech\u00e1nov\u00e1","year":"2004","unstructured":"Pech\u00e1nov\u00e1, O., Dobesov\u00e1, Z., Cejka, J., Kunes, J. & Zicha, J. Vasoactive systems in L-name hypertension: the role of inducible nitric oxide synthase. J. Hypertens. 22, 167\u2013173 (2004).","journal-title":"J. Hypertens."},{"key":"4895_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74011-1","volume":"10","author":"Z Wu","year":"2020","unstructured":"Wu, Z. et al. Inhibition of Enos by L-name resulting in rat hind limb developmental defects through Pfkfb3 mediated angiogenetic pathway. Sci. Rep. 10, 16754 (2020).","journal-title":"Sci. Rep."},{"key":"4895_CR20","doi-asserted-by":"publisher","first-page":"e0125437","DOI":"10.1371\/journal.pone.0125437","volume":"10","author":"IJ Zamora","year":"2015","unstructured":"Zamora, I. J. et al. Low abdominal Nirs values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis. PLoS ONE 10, e0125437 (2015).","journal-title":"PLoS ONE"},{"key":"4895_CR21","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1542\/peds.98.4.706","volume":"98","author":"AP Goldman","year":"1996","unstructured":"Goldman, A. P., Tasker, R. C., Haworth, S. G., Sigston, P. E. & Macrae, D. J. Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 98, 706\u2013713 (1996).","journal-title":"Pediatrics"},{"key":"4895_CR22","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1378\/chest.120.2.573","volume":"120","author":"H Maurenbrecher","year":"2001","unstructured":"Maurenbrecher, H., Lamy, M., Deby-Dupont, G., Frascarolo, P. & Hedenstierna, G. An animal model of response and nonresponse to inhaled nitric oxide in endotoxin-induced lung injury. Chest 120, 573\u2013581 (2001).","journal-title":"Chest"},{"key":"4895_CR23","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1515\/jpm-2015-0210","volume":"44","author":"AA Morel","year":"2016","unstructured":"Morel, A. A. et al. Clinical characteristics and factors associated with term and late preterm infants that do not respond to inhaled nitric oxide (Ino). J. Perinat. Med. 44, 663\u2013668 (2016).","journal-title":"J. Perinat. Med."},{"key":"4895_CR24","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1067\/mpd.2000.109145","volume":"137","author":"RM Becker","year":"2000","unstructured":"Becker, R. M. et al. Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J. Pediatr. 137, 785\u2013793 (2000).","journal-title":"J. Pediatr."},{"key":"4895_CR25","doi-asserted-by":"publisher","first-page":"G638","DOI":"10.1152\/ajpgi.00198.2018","volume":"315","author":"JL Robinson","year":"2018","unstructured":"Robinson, J. L. et al. Prematurity reduces citrulline-arginine-nitric oxide production and precedes the onset of necrotizing enterocolitis in piglets. Am. J. Physiol. Gastrointest. Liver Physiol. 315, G638\u2013g649 (2018).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"4895_CR26","first-page":"Cd004339","volume":"4","author":"PS Shah","year":"2017","unstructured":"Shah, P. S., Shah, V. S. & Kelly, L. E. Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst. Rev. 4, Cd004339 (2017).","journal-title":"Cochrane Database Syst. Rev."},{"key":"4895_CR27","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/nrd2466","volume":"7","author":"JO Lundberg","year":"2008","unstructured":"Lundberg, J. O., Weitzberg, E. & Gladwin, M. T. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 7, 156\u2013167 (2008).","journal-title":"Nat. Rev. Drug Discov."},{"key":"4895_CR28","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1203\/00006450-199607000-00025","volume":"40","author":"U Schedin","year":"1996","unstructured":"Schedin, U., Norman, M., Gustafsson, L. E., Herin, P. & Frostell, C. Endogenous nitric oxide in the upper airways of healthy newborn infants. Pediatr. Res. 40, 148\u2013151 (1996).","journal-title":"Pediatr. Res."},{"key":"4895_CR29","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1164\/ajrccm.156.2.9601056","volume":"156","author":"X Combes","year":"1997","unstructured":"Combes, X., Mazmanian, M., Gourlain, H. & Herve, P. Effect of 48\u2009h of nitric oxide inhalation on pulmonary vasoreactivity in rats. Am. J. Respir. Crit. Care Med. 156, 473\u2013477 (1997).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"4895_CR30","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1097\/00003246-200006000-00006","volume":"28","author":"BH Cuthbertson","year":"2000","unstructured":"Cuthbertson, B. H., Galley, H. F. & Webster, N. R. Effect of inhaled nitric oxide on key mediators of the inflammatory response in patients with acute lung injury. Crit. Care Med. 28, 1736\u20131741 (2000).","journal-title":"Crit. Care Med."},{"key":"4895_CR31","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1046\/j.1423-0410.2002.00223.x","volume":"83","author":"F Torella","year":"2002","unstructured":"Torella, F., Haynes, S. L. & McCollum, C. N. Cerebral and peripheral near-infrared spectroscopy: an alternative transfusion trigger? Vox Sang. 83, 254\u2013257 (2002).","journal-title":"Vox Sang."},{"key":"4895_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101238","volume":"26","author":"T Liu","year":"2019","unstructured":"Liu, T. et al. L-name releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation. Redox Biol. 26, 101238 (2019).","journal-title":"Redox Biol."},{"key":"4895_CR33","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1161\/HYPERTENSIONAHA.120.15491","volume":"76","author":"JF Smith","year":"2020","unstructured":"Smith, J. F. et al. Endothelial nitric oxide suppresses action-potential-like transient spikes and vasospasm in small resistance arteries. Hypertension 76, 785\u2013794 (2020).","journal-title":"Hypertension"},{"key":"4895_CR34","doi-asserted-by":"crossref","unstructured":"Wong, V. W. & Lerner, E. Nitric Oxide Inhibition Strategies. Future Sci. OA 1, FSO35 (2015).","DOI":"10.4155\/fso.15.35"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04895-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04895-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04895-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:53:38Z","timestamp":1773287618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-026-04895-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":34,"alternative-id":["4895"],"URL":"https:\/\/doi.org\/10.1038\/s41390-026-04895-8","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"assertion":[{"value":"24 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}