Xiaoyi Yu1, Andrei Radulescu, Nicholas Zorko, Gail E Besner. 1. Department of Pediatric Surgery, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, and Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
Abstract
BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates. Although the exact etiology remains unknown, decreased intestinal blood flow is believed to play a critical role. We have shown that heparin-binding epidermal growth factor-like growth factor (HB-EGF) protects the intestines from injury in a rodent model of NEC. Our current goal was to assess the effect of HB-EGF on intestinal microvascular blood flow and intestinal injury in rat pups subjected to experimental NEC. METHODS: Newborn rat pups were subjected to stress by exposure to hypoxia, hypothermia, hypertonic feedings, and lipopolysaccharide, with some pups receiving HB-EGF (800 microg x kg(-1) x dose(-1)) added to the feeds. Control animals received breast milk. Intestinal injury was graded using a standard histologic injury scoring system. Microvascular blood flow was assessed by fluorescein isothiocyanate/dextran angiography, with fluorescent images subjected to quantification, and by scanning electron microscopy. RESULTS: Intestinal microvascular blood flow (defined as the extent of vascular filling with fluorescein isothiocyanate/dextran) was significantly decreased in pups subjected to stress compared with breast-fed pups. Stressed pups treated with HB-EGF had significantly increased microvascular blood flow. The changes in villous microvasculature correlated with histologic injury scores, with stressed pups treated with HB-EGF showing decreased histologic injury. CONCLUSIONS: HB-EGF significantly preserved intestinal microvascular blood flow in pups subjected to experimental NEC, indicating that HB-EGF may play a critical role in the treatment of various diseases manifested by decreased intestinal blood flow, including NEC.
BACKGROUND & AIMS:Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates. Although the exact etiology remains unknown, decreased intestinal blood flow is believed to play a critical role. We have shown that heparin-binding epidermal growth factor-like growth factor (HB-EGF) protects the intestines from injury in a rodent model of NEC. Our current goal was to assess the effect of HB-EGF on intestinal microvascular blood flow and intestinal injury in rat pups subjected to experimental NEC. METHODS: Newborn rat pups were subjected to stress by exposure to hypoxia, hypothermia, hypertonic feedings, and lipopolysaccharide, with some pups receiving HB-EGF (800 microg x kg(-1) x dose(-1)) added to the feeds. Control animals received breast milk. Intestinal injury was graded using a standard histologic injury scoring system. Microvascular blood flow was assessed by fluorescein isothiocyanate/dextran angiography, with fluorescent images subjected to quantification, and by scanning electron microscopy. RESULTS: Intestinal microvascular blood flow (defined as the extent of vascular filling with fluorescein isothiocyanate/dextran) was significantly decreased in pups subjected to stress compared with breast-fed pups. Stressed pups treated with HB-EGF had significantly increased microvascular blood flow. The changes in villous microvasculature correlated with histologic injury scores, with stressed pups treated with HB-EGF showing decreased histologic injury. CONCLUSIONS:HB-EGF significantly preserved intestinal microvascular blood flow in pups subjected to experimental NEC, indicating that HB-EGF may play a critical role in the treatment of various diseases manifested by decreased intestinal blood flow, including NEC.
Authors: Zheng Gang Zhang; Li Zhang; Wayne Tsang; Hamid Soltanian-Zadeh; Daniel Morris; Ruilan Zhang; Anton Goussev; Cecylia Powers; Thomas Yeich; Michael Chopp Journal: J Cereb Blood Flow Metab Date: 2002-04 Impact factor: 6.200
Authors: Y Matsumoto; K Kanamoto; K Kawakubo; H Aomi; T Matsumoto; S Ibayashi; M Fujishima Journal: Am J Physiol Gastrointest Liver Physiol Date: 2001-05 Impact factor: 4.052
Authors: M Ann Kuhn; Guilang Xia; Veela B Mehta; Sandra Glenn; Marc P Michalsky; Gail E Besner Journal: Antioxid Redox Signal Date: 2002-08 Impact factor: 8.401
Authors: Andrei Radulescu; Hong-Yi Zhang; Xiaoyi Yu; Jacob K Olson; Amanda K Darbyshire; Yan Chen; Gail E Besner Journal: J Pediatr Surg Date: 2010-10 Impact factor: 2.545
Authors: Ibrahim Yazji; Chhinder P Sodhi; Elizabeth K Lee; Misty Good; Charlotte E Egan; Amin Afrazi; Matthew D Neal; Hongpeng Jia; Joyce Lin; Congrong Ma; Maria F Branca; Thomas Prindle; Ward M Richardson; John Ozolek; Timothy R Billiar; David G Binion; Mark T Gladwin; David J Hackam Journal: Proc Natl Acad Sci U S A Date: 2013-05-06 Impact factor: 11.205
Authors: Timothy L Denning; Amina M Bhatia; Andrea F Kane; Ravi M Patel; Patricia W Denning Journal: Semin Perinatol Date: 2016-12-09 Impact factor: 3.300