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. CONCLUSION PRBC transfusion in enterally fed preterm lambs promotes mesenteric vasoconstriction and impairs vasorelaxation by reducing mesenteric arterial eNOS.

Effect of blood transfusion on intestinal blood flow and oxygenation in extremely preterm infants during first week of life

“…The effect of blood transfusion on splanchnic vasculature is reliant on the balance between mesenteric vasoconstriction and relaxation induced by intestinal endothelial production of nitric oxide. A recent study has shown blood transfusion in enterally fed preterm lambs (n = 16) promotes mesenteric vasoconstriction and impairs vasorelaxation by reducing mesenteric arterial endothelial nitric oxide synthase …”

Fetal and postnatal ovine mesenteric vascular reactivity

“…The number of subjects in each group is small. However, we performed a power analysis of our study using previous published data demonstrating that vasoconstriction to NE is normally distributed with a standard deviation of 401 g/g force in 134-d gestation lambs (6). To detect a difference of 800 g/g force of contraction between the groups, we needed at least four lambs in each group.…”

“…A temporal association between packed red blood cell transfusion and NEC has been reported (4,5). Packed red blood cell transfusion has also been shown to increase mesenteric arterial (MA) contractility in preterm fed lambs (6). NO is thought to play a key role as a molecular signaling “hub” in the generation of gut barrier failure in NEC (7) as well as in the pathogenesis of transfusion-associated gut injury (8).…”

Necrotising Enterocolitis - epidemiology and imaging

“…30 An alternative explanation is an immunologic influence working through mesenteric arterial reactivity and nitric oxide pathways as investigated in premature lambs. 173 So far, however, evidence has been equivocal, 174,175 and a recent meta-analysis, found that the quality of the studies on transfusion induced NEC was generally low.…”