Selective microvascular endothelial cell dysfunction in the small intestine following resuscitated hemorrhagic shock

Following resuscitation (RES) from hemorrhagic shock (HEM), intestinal micr ovessels develop progressive vasoconstriction that impairs mucosal blood fl ow, despite central hemodynamic RES. These events might have clinical conse quences secondary to occult intestinal ischemia. We hypothesized that the m icrovascular impairments were due to progressive endothelial cell dysfuncti on and an associated reduction in the dilator, nitric oxide (NO), following HEM/RES. Male Sprague-Dawley rats, were monitored for central hemodynamics and the terminal ileum was studied with in vivo videomicroscopy. HEM was 5 0% of baseline mean arterial pressure (MAP) for 60 min, and RES was with sh ed blood + I Volume of normal saline (NS). Following HEM/RES, acetylcholine (10(-7), 10(-5) M) was topically applied and ileal inflow (Al) and premuco sal arteriolar diameters were measured to assess endothelial-cell function at 60 and 120 min post-RES. Normalization of MAP, cardiac output, and heart rate demonstrated adequate systemic resuscitation. Post-RES vasoconstricti on developed in Al (-25%) and premucosal (-28%) arterioles with an associat ed reduction in Al flow (-47%). However, there was a selective impairment o f endothetial-dependent dilation that was manifested only in the smaller pr emucosal arterioles and not in the inflow, Al arterioles. This suggests tha t multiple mechanisms are involved in the development of the post-RES vasoc onstriction. The premucosal response was likely mediated by endothelial cel l dysfunction, while the Al response was probably the result of enhanced va soconstrictor forces. This early microvascular dysfunction might contribute to the late sequelae of intestinal ischemia and might alter microvascular responses to subsequent systemic insults.