Heparin-Binding EGF-Like Growth Factor Increases Intestinal Microvascular Blood Flow in Necrotizing Enterocolitis

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 mu g . kg(-1) . 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 isothlocyanare/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.