The Effect of S‐Nitroso‐Glutathione on Platelet and Leukocyte Function During Experimental Extracorporeal Circulation

Abstract

Treatment with extracorporeal membrane oxygenation ECMO) is associated with side effects, e.g., blood cell consumption and activation. Our group has earlier shown that nitric oxide administered as a gas reduces platelet consumption and activation. In the present work we have studied the effect of the NO-donor S-nitroso-glutathione GSNO) on platelets and leukocytes in an in vitro extracorporeal circuit. Two complete ECMO circuits were perfused with fresh heparinized human blood for 24 hours. GSNO was administered as a continuous infusion to one circuit at a rate of 0.7 mg/hour in four paired experiments and at a rate of 3.5 mg/hour in another four paired experiments. The other circuit was used as a control. Blood samples were withdrawn from both circuits before the start of the experiments and at 0.5, 1, 3, 12, and 24 hours of perfusion. The samples were analyzed for red blood cell count, leukocyte count, platelet count, platelet membrane expression of glycoproteins GP) Ib and GPIIb/IIIa, leukocyte membrane expression of cluster of differentiation CD) 11b/CD18, as well as plasma concentration of tumor necrosis factor TNF)-alpha, interleukin IL)-1beta, and IL-8. No difference in these parameters between the GSNO and the control circuit at any time point was assayed. In this study, no significant effect of GSNO on circulating platelets or leukocytes during experimental extracorporeal circulation could be shown.

The mediation of platelet quiescence by NO-releasing polymers via cGMP-induced serine 239 phosphorylation of vasodilator-stimulated phosphoprotein

“…Previous work, including ours, has established that NO releasing polymers (NORel) can prevent loss of circulating platelets and monocytes in the RT model and limited clinical ECLS [6, 27, 28]. These experiments demonstrate significant evidence for the importance of NO in defining, in part, the hemocompatibility of biomaterials used in ECLS and mimicking NO released from normal functioning vascular endothelium.…”

Current Understanding of Leukocyte Phenotypic and Functional Modulation During Extracorporeal Membrane Oxygenation: A Narrative Review

“…and partially observed by Ki et al. ( 32 , 33 , 37 ). The discrepancies between the outcomes could be rationalized by the utilization of different ECMO technology, model setup, and blood flow rates.…”

“…However, the effect of ECMO on L-selectin (CD62L), another key adhesion molecule, remains debatable. Three studies independently reported either a reduced, augmented, or no change in expression of L-selectin at the initial hours of ECMO ( 18 , 32 , 33 ). Observed discrepancies may be associated with the differences between human, porcine and ex vivo ECMO.…”

“…An early ex vivo ECMO study has also highlighted the potential importance of delivery methods when using supplemental gas to improve biological and clinical outcomes (e.g. direct infusion into circulating blood versus administrating into the oxygenator) ( 33 ). The benefit of nitric oxide administration into the oxygenator in patients undergoing cardiac surgery has been demonstrated with improved outcomes in a number of randomized control trials ( 115 , 116 ).…”

Artificial Organs 2003: A Year in Review

“…Katrin Adrian et al of The Queen Silvia Children's Hospital (Göteborg, Sweden) studied the effect of nitric oxide‐donor S‐nitroso‐glutathione (GSNO) on platelets and leukocytes in an in vitro extracorporeal circuit (138). No significant effect of GSNO on circulating platelets or leukocytes during experimental extracorporeal circulation was shown indicating that a continuous infusion of GSNO would probably not be helpful during clinical cardiopulmonary bypass on ECMO.…”