A Non‐invasive Novel Method to Assess Necrotizing Enterocolitis in Rodents

Necrotizing enterocolitis (NEC) is the leading cause of mortality due to gastrointestinal (GI) disease in premature neonates. The precise pathogenesis of NEC is unknown, but early stages are thought to be characterized by damage to the intestinal mucosa and changes to the microbiota; while full intestinal necrosis, perforation, and multi‐system failure occur during the later stages. The early diagnosis of NEC would drastically reduce morbidity and mortality, but there are currently no predictive tests available to clinicians. Heart rate variability (HRV) is a non‐invasive way to measure changes in vagal tone, and our laboratory has shown that the high frequency power spectra, an indicator of vagal tone, is a useful factor to predict NEC in neonates before the onset of clinical symptoms (Doheny et al. Neurogastroenterol. Motil. , 2014). Technical issues prevent the same power analysis in rodents; however, time‐domain analysis of HRV analyzes inter‐beat‐interval differences (IBID) to discriminate vagal tone. Our unpublished data indicate a correlation between IBID and GI motility, thus validating the usefulness of cardiac vagal tone measures as a non‐invasive indicator of GI motility (Meister and Travagli, unpublished). In the present work we hypothesize that: i) in rodents IBID is a valid marker of NEC; and, ii) the alterations of the neurochemical phenotype of myenteric and vagal preganglionic neurons are proportional to the severity of NEC. Increasing severity stages of NEC are induced in newborn Sprague‐Dawley rats including i) mild NEC (

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