The Journal of Pediatrics
Volume 150, Issue 1 , Pages 5-6, January 2007

The Vascular Contribution to Necrotizing Enterocolitis

  • Rosemary D. Higgins, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Dr Rosemary D. Higgins, Program Scientist for the Neonatal Research Network, Pregnancy and Perinatology Branch, Center for Developmental Biology and Perinatal Medicine, NICHD, NIH, 6100 Executive Blvd., Room 4B03B, MSC 7510, Bethesda, MD 20892.

National Institutes of Health, Bethesda, MD

Article Outline

Abbreviations: eNOS, Endothelial nitric oxide synthase, NEC, Necrotizing entercolitis

 

Feeding, gastrointestinal bacterial colonization, gut motility, cytokines, vascular factors, and gut blood flow all have been implicated in the etiology and pathogenesis of necrotizing entercolitis (NEC). Further, neonatal complications such as respiratory distress syndrome, respiratory disease, apnea, infection, hypotension, asphyxia, and patent ductus arteriosus increase the risk for development of NEC. Infants with NEC generally present with feeding intolerance, abdominal distension, bilious gastric residuals or vomiting, or bloody stools. Nonspecific presenting signs and symptoms include apnea, bradycardia, desaturation episodes, cyanosis, lethargy, temperature instability, poor peripheral perfusion, hypoglycemia, jaundice, and shock. Diagnosis of NEC is confirmed by the presence of the classic finding of pneumatosis intestinalis on abdominal x-ray. Associated laboratory abnormalities can include metabolic acidosis, leukopenia, thrombocytopenia, anemia, and clotting abnormalities of disseminated intravascular coagulation. Treatment consists of supportive medical care and surgical care.

See related article, p 40

Vascular flow to the gastrointestinal tract plays a significant role in gut development, integrity, and function. Blood flow is balanced between needs of the bowel and needs for blood flow to other organs. Control of blood flow, specifically the balance between vasoconstriction and vasodilatation plays a key role in maintaining gut integrity. Nowicki et al1 should be commended for their report, published in this issue of the Journal, in delineating the role of endothelial nitric oxide synthase (eNOS) in NEC. This is the first study to demonstrate reduced eNOS function in human tissue samples from patients with NEC.

Nowicki et al show that eNOS activity and NO production are decreased in the arterioles of infants with NEC.1 The lack of function of a vasodilatory regulator certainly adds to the description of lack of appropriate flow to the bowel in the etiology and pathogenesis of NEC. Increased endothelin results in significant vasoconstriction that is not able to be reversed in the arterioles of the small intestine with NEC. Nowicki et al2 previously provided evidence that intestinal tissue from patients with NEC had higher concentrations of endothelin. The balance between vasoconstriction and vasodilatation is critical in assuring bowel homeostasis.

Perhaps modulation of eNOS function may be one modality to target increasing blood flow in ischemic bowel. Possibly, infants who develop NEC have genetic susceptibility factors that render them vulnerable to NEC, specifically related to eNOS or endothelin expression. Conversely, those infants who do not develop NEC may have genetic protective factors.

Vascular control of blood vessel diameter is paramount to appropriate blood flow. Lack of appropriate physiologic evidence of eNOS function in gut vessels of infants with NEC is a new finding. It remains to be seen whether or not these are innate genetic differences in eNOS expression and response, or whether this lack of eNOS expression and function is induced in the infant at risk for NEC. Perhaps an environmental trigger in susceptible infants occurs in the pathway to NEC.

Other factors including tissue oxygen levels, cytokines, vasoactive agents, and factors that can enhance or reduce blood flow are likely to play a role in control of vasoconstriction and vasodilatation in mesenteric circulation. Circulatory responses to factors that affect mesenteric vascular flow have previously been implication in neonatal disease.3 Injury and reperfusion are also likely to be involved in the cascade of events that results in NEC.

NEC remains a dreadful disease in the neonatal intensive care unit. A brief lack of blood flow to the bowel or alteration of mucosal integrity can change an infant’s destiny. The research direction needed for NEC involves identification of children at high risk and prevention of this devastating disease. Identification may potentially be accomplished by newer methods of genomic and proteomic identification and risk interactions with the environment. Prevention of NEC remains a challenge.

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References 

  1. Nowicki PT, Caniano DM, Hammond S, Giannone PJ, Besner G, Reber KM, et al. Endothelial nitric oxide synthase in human intestine resected for necrotizing enterocolitis. J Pediatr. 2006;150:40
  2. Nowicki PT, Dunaway DJ, Nankervis CA, Giannone PJ, Reber KM, Hammond SB, et al. Endothelin-1 in human intestine resected for necrotizing enterocolitis. J Pediatr. 2005;146:805–810
  3. Cheung PY, Barrington KJ, Bigam DL. Temporal effects of prolonged hypoxaemia and reoxygenation on systemic, pulmonary and mesenteric perfusions in newborn piglets. Cardiovasc Res. 1998;39:451–458

PII: S0022-3476(06)01013-4

doi:10.1016/j.jpeds.2006.10.063

Refers to article:

  • Endothelial Nitric Oxide Synthase in Human Intestine Resected for Necrotizing Enterocolitis

    Philip T. Nowicki, Donna A. Caniano, Sue Hammond, Peter J. Giannone, Gail E. Besner, Kristina M. Reber, Craig A. Nankervis
    The Journal of Pediatrics January 2007 (Vol. 150, Issue 1, Pages 40-45)

The Journal of Pediatrics
Volume 150, Issue 1 , Pages 5-6, January 2007

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