Altered intestinal microcirculation is the critical event in the development of necrotizing enterocolitis

The pathophysiology of necrotizing enterocolitis (NEC) includes prematurity, enteral feeds, hypoxia, and hypothermia. We hypothesized that vasoconstriction of the neonatal intestinal microvasculature is the essential mechanistic event in NEC and that these microvascular changes correlate with alterations in mediators of inflammation.

Sprague-Dawley rat pups were separated into groups by litter. Necrotizing enterocolitis was induced in experimental groups, whereas control animals were delivered vaginally and dam fed. Neonatal pups underwent intravital videomicroscopy of the terminal ileum with particular attention to the inflow and premucosal arterioles. Reverse transcriptase-polymerase chain reaction was performed to evaluate for messenger RNA of mediators of inflammation.

Necrotizing enterocolitis animals demonstrated statistically significant smaller inflow and premucosal arterioles than control animals (P < .05). Necrotizing enterocolitis animals had an altered intestinal arteriolar flow with a distinct "stop-and-go" pattern, suggesting severe vascular dysfunction. Reverse transcriptase-polymerase chain reaction confirmed elevation of Toll-like receptor 4 (P = .01) and high-mobility group box protein 1 (P = .001) in the ileum of animals with NEC.

Intestinal arterioles were significantly smaller at baseline in animals with NEC compared with controls, and expression of inflammatory mediators was increased in animals with NEC. This represents a novel method of defining the pathophysiology of NEC and allows real-time evaluation of novel vasoactive strategies to treat NEC.