Heparin-binding EGF-like growth factor preserves mesenteric microcirculatory blood flow and protects against intestinal injury in rats subjected to hemorrhagic shock and resuscitation

Abstract

The gut is highly susceptible to injury after hemorrhagic shock and resuscitation (HS/R) because of progressive mesenteric hypoperfusion. The aim of the current study was to evaluate the effect of heparin-binding EGF-like growth factor (HB-EGF) on mesenteric microcirculatory blood flow and intestinal injury in rats subjected to HS/R. HS/R was induced in adult rats, with some rats receiving HB-EGF (600 mug/kg) IV at the onset of resuscitation (HS/R+HB-EGF) and others receiving vehicle only (HS/R). FITC-dextran was administered intra-arterially to evaluate mesenteric microcirculation, and intestinal damage and restitution were evaluated histologically. Data were expressed as mean +/- SE, with P < .05 considered statistically significant. Microcirculatory blood flow was significantly reduced 1 hour after HS/R. HS/R+HB-EGF rats had significantly increased microcirculatory flow compared with HS/R rats at 1 hour (4.5 +/- 0.43 vs 2.64 +/- 0.46, P < .05) and 3 hours (8.04 +/- 1.58 vs 2.89 +/- 0.63, P < .05) after HS/R. HS/R+HB-EGF rats had significantly less intestinal damage compared with HS/R rats 3 hours after resuscitation (2.04 +/- 0.5 vs 3.08 +/- 0.5, P < .05), along with significantly fewer incompetent (nonresurfaced, nonhealed) villi, which is indicative of improved restitution. HB-EGF significantly improved postresuscitation microcirculatory blood flow in rats subjected to HS/R, associated with significantly decreased intestinal damage and increased restitution. These results suggest that HB-EGF may be a useful therapeutic agent that improves intestinal blood flow in patients with intestinal injury secondary to hemorrhagic shock.