Heparin-Binding Epidermal Growth Factor-Like Growth Factor Protects Rat Intestine from Ischemia/Reperfusion Injury

• Published in: The Journal of surgical research Vol. 87; no. 2; pp. 225 - 231
• Main Authors: Pillai, Srikumar B., Hinman, Christina E., Luquette, Mark H., Nowicki, Philip T., Besner, Gail E.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-1999; Elsevier
• Subjects: Acute Disease; Animals; Biological and medical sciences; Cytoprotection; Digestive system; Epidermal Growth Factor - metabolism; Epidermal Growth Factor - pharmacology; epidermal growth factor receptor; Gastroenterology. Liver. Pancreas. Abdomen; Heparin-binding EGF-like Growth Factor; heparin-binding epidermal growth factor-like growth factor; Intercellular Signaling Peptides and Proteins; intestine; Intestines - blood supply; Ischemia - drug therapy; Ischemia - mortality; ischemia/reperfusion injury; Medical sciences; mucosa; Other diseases. Semiology; Pharmacology. Drug treatments; protection; Rats; Rats, Sprague-Dawley; Receptor, Epidermal Growth Factor - metabolism; Reperfusion Injury - prevention & control; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; protection; intestine; heparin-binding epidermal growth factor-like growth factor; ischemia/reperfusion injury; mucosa; epidermal growth factor receptor; Chemoprophylaxis; Rat; Cytokine; Rodentia; Gut; Cardiovascular disease; Anticoagulant; Experimental study; Vertebrata; Mammalia; Epidermal growth factor; Reperfusion; Treatment; Ischemia; Polypeptide; Animal; Digestive diseases; Intestinal disease; Glycosaminoglycan; Heparin; Growth factor
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1999.5764

Background. We have shown previously that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is cytoprotective for intestinal epithelial cells exposed to hypoxia in vitro. We now examine the effects of HB-EGF on the recovery of small intestine from ischemic injury in vivo.
Methods. Segmental intestinal ischemia of 60-min duration was produced in adult rats by occlusion of a first-order branch of the superior mesenteric artery. Recombinant HB-EGF (100 μg) was injected intraluminally into the proximal small bowel after 45 min of ischemia in experimental animals, and buffered saline was injected in control animals. Animals were sacrificed after 48 h, and the affected bowel was resected, processed, and examined microscopically, with histologic grading of the ischemic injury. Additional animals were allowed to recover for up to 1 month to evaluate mortality differences.
Results. Intraluminal administration of HB-EGF resulted in significantly decreased extent and severity of ischemia/reperfusion injury, with significantly decreased grade of injury in the HB-EGF-treated compared with nontreated animals (average injury grade 0.66 compared with 2.44, respectively). Moreover, the mortality rate was significantly lower in the HB-EGF-treated animals compared with nontreated animals (0% vs 25%, respectively). HB-EGF-treated animals had increased weight gain in the postischemia recovery period.
Conclusions. We conclude that HB-EGF, given intraluminally, reduces both the amount and the severity of ischemia/reperfusion injury in the small bowel, reduces the mortality associated with intestinal ischemia, and may enhance intestinal recovery. The in vitro and in vivo cytoprotective effects of this growth factor suggest that it may, in the future, be clinically useful in treating patients with intestinal ischemia.