Heparin-binding EGF-like growth factor increases intestinal microvascular blood flow in necrotizing enterocolitis.
OBJECTIVE
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.
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.
Xiaoyi
X
Yu
Andrei
A
Radulescu
Nicholas
N
Zorko
Gail E
GE
Besner
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D005451:Fluorescein Angiography; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000648:ultrastructure; D007422:Intestines / Q000098:blood supply* / Q000648:ultrastructure; D008833:Microcirculation; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013152:Splanchnic Circulation; D014699:Venules / Q000378:metabolism / Q000503:physiopathology
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins