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 towards 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.

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

“…The potential for injury resulting from insufficient mucus layer protection is heightened by the impaired clearance of luminal contents, owing to decreased motility 78–80,83 and decreased digestion and absorption as a result of enterocyte immaturity 76,77 . Other important differences in the intestine of premature infants compared with full-term infants include increased microvascular tone within the intestinal mesentery 66,84 and the presence of immature tight junctions 85,86 , all of which can render the bowel at risk of proinflammatory signalling, bacterial translocation and NEC development 74,78,84 . Notably, some of these important factors are linked to TLR4 signalling.…”

The relation between splanchnic ischaemia and intestinal damage in necrotising enterocolitis

“…The role of intestinal perfusion in the underlying pathophysiology of NEC remains incompletely understood 2 3…”

Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

“…1–3 Mucosal wounds associated with inflammatory disorders compromise this critical epithelial barrier, undermine gut barrier function and allow bacterial translocation and absorption of toxins, antigens, proteases and other macromolecules, leading to local infection followed by distant organ pathology. In response to injury, rapid re-establishment of epithelial barrier function by intestinal epithelial cells (IEC) depends on migration of uninjured IEC to cover denuded sections of basement membrane.…”