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We hypothesized that NEC induction in rat pups decreases HF\u2010HRV power; subdiaphragmatic vagotomy worsens the severity of the NEC phenotype, increases levels of pro\u2010inflammatory cytokines, and alters the myenteric phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Newborn Sprague\u2010Dawley rats, representative of preterm human neonates, were subjected to 7\u20108\u00a0days of brief periods of cold stress and hypoxia to induce NEC with or without unilateral subdiaphragmatic vagotomy. HRV was measured at postnatal days one and five, pups were sacrificed at day 8\/9, and gastrointestinal tissues and blood were collected for immunohistochemical, corticosterone, and cytokine analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Compared to control, NEC\u2010induced rats showed the following: (a) typical histological signs of grade 2 NEC, which were more severe in rats that underwent vagotomy; (b) reduced developmental increases in time (RMSSD) and frequency (HF) HRV spectra when combined with the stress of laparotomy\/vagotomy; (c) increases in nitric oxide synthase\u2010immunoreactivity in the myenteric plexus of jejunum and ileum; furthermore, compared to mild NEC and controls, vagotomized NEC rats had increased plasma values of pro\u2010inflammatory cytokines IL\u20101\u03b2 and IL\u20106.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>Our data suggest that in rodents, similar to neonatal observations, NEC induction attenuated developmental HF\u2010HRV increases, furthermore, subdiaphragmatic vagotomy worsened the histological severity, increased pro\u2010inflammatory cytokines, and altered the nitrergic myenteric phenotype, suggesting a role of the vagus in the development of NEC pathology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13484","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T05:39:50Z","timestamp":1539063590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Necrotizing enterocolitis attenuates developmental heart rate variability increases in newborn rats"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4563-2127","authenticated-orcid":false,"given":"Alissa L.","family":"Meister","sequence":"first","affiliation":[{"name":"Neural and Behavioral Sciences Penn State College of Medicine Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-0697","authenticated-orcid":false,"given":"Kim K.","family":"Doheny","sequence":"additional","affiliation":[{"name":"Neural and Behavioral Sciences Penn State College of Medicine Hershey Pennsylvania"},{"name":"Neonatal\u2010Perinatal Medicine Penn State College of Medicine Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-7683","authenticated-orcid":false,"given":"R. 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