The role of the intestinal microcirculation in necrotizing enterocolitis

Abstract

Necrotizing enterocolitis (NEC) continues to be a devastating inflammatory disease of the newborn intestine. Despite advances in management, morbidity and mortality remain high. While it is clear that intestinal ischemia plays a large role in disease pathogenesis, attempts to link NEC to intestinal macrovascular derangement have been largely unsuccessful. More recently, there has been a concerted effort to characterize the pathologic changes of the intestinal microcirculation in response to intestinal injury, including NEC. This microcirculatory regulation is controlled by a balance of vasoconstrictor and vasodilator forces. Vasoconstriction is mediated primarily by endothelin-1 (ET-1), while vasodilation is mediated primarily by nitric oxide (NO). These chemical mediators have been implicated in many aspects of intestinal ischemic injury and NEC, with the balance shifting toward increased vasoconstriction associated with intestinal injury. With a proper understanding of these antagonistic forces, potential therapeutic avenues may result from improving this pathologic microcirculatory dysregulation.

Figure 1. Schematic representation of the intestinal microcirculation

Small mesenteric arteries pierce the muscularis layers and terminate in the submucosa where they give rise to 1A (1^st order) arterioles. 2A (2^nd order) arterioles arise from 1A arterioles. Although not shown here, these 2A arterioles merge with several 1A arterioles, thus generating an arteriolar plexus that serves to pressurize the terminal downstream microvasculature. 3A (3^rd order) arterioles arise from 2A arterioles and proceed to the mucosa, giving off a 4A branch just before descent into the mucosa. The 4A vessels travel to the muscularis layers. Each 3A vessel becomes the single arteriole perfusing each villus. Reprinted with permission.