title: Packed red cell transfusions alter mesenteric arterial reactivity and nitric oxide pathway in preterm lambs.
abstract: BACKGROUND
  Cases of necrotizing enterocolitis occurring within 48 h of packed red blood cell (PRBC) transfusions are increasingly being described in observational studies. Transfusion-associated gut injury is speculated to result from an abnormal mesenteric vascular response to transfusion. However, the mechanism of disruption of the balance between mesenteric vasoconstriction and relaxation following transfusion is not known.
  
  
  METHODS
  Preterm lambs (n = 16, 134 d gestation; term: 145-147 d) were delivered and ventilated for 24 h. All the lambs received orogastric feeds with colostrum. In addition, 10 of these lambs received PRBC transfusions. Vasoreactivity was evaluated in isolated mesenteric arterial rings using norepinephrine and endothelin-1 as vasoconstrictors. Endothelium-dependent (A23187, a calcium ionophore) and endothelium-independent (SNAP) nitric oxide (NO) donors were used as vasorelaxants. Mesenteric arterial endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase 5 (PDE5) mRNA analyses and protein assays were performed.
  
  
  RESULTS
  Transfusion with PRBC significantly increased mesenteric vasoconstriction to norepinephrine and endothelin-1 and impaired relaxation to A23187 and SNAP. Mesenteric arterial eNOS protein decreased following PRBC transfusion. No significant changes were noted in sGC and PDE5 mRNA or protein assays.
  
  
  CONCLUSIONS
  PRBC transfusion in enterally fed preterm lambs promotes mesenteric vasoconstriction and impairs vasorelaxation by reducing mesenteric arterial eNOS.
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Jayasree
authors.initials: J
authors.lastname: Nair
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Sylvia F
authors.initials: SF
authors.lastname: Gugino
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Nielsen
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Allen
authors.affiliation: 1] Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York [2] Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York.
authors.forename: James A
authors.initials: JA
authors.lastname: Russell
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Bobby
authors.initials: B
authors.lastname: Mathew
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Swartz
authors.affiliation: Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Satyan
authors.initials: S
authors.lastname: Lakshminrusimha
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017707:Erythrocyte Transfusion; D005260:Female; D008638:Mesenteric Arteries / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D012756:Sheep
chemical_list: D009569:Nitric Oxide