Investigating S-nitrolysation (sno) As A Possible Therapy To Enhance Microvasculature And Tissue Perfusion In Vca Donors: A Study On Human Brain Death Donor
Mohamed Awad1, Arvin Smith, MS1, James Reynolds, PhD2, Anand Kumar, MD1.
1Case Western Reserve University, Cleveland, OH, USA, 2Case Western Reserve University, cleveland, OH, USA.
Introduction: Tissue ischemia/hypoxia secondary to brain death pathophysiology in Vascularized Composite Allotransplanation(VCA) remains understudied. A deficiency of nitric oxide (NO) supply in hypoxic tissue may decrease microvascular perfusion in donor tissue. S-nitrosothiols (SNOs) are NO carrying molecules produced endogenously on red blood cells that improve blood flow and oxygen delivery in the microcirculation and are a novel therapeutic target for the treatment of brain death related VCA tissue hypoxia. We hypothesize that 1) brain death is associated with decreased levels of SNO‐Hb in the microcirculation and 2) decreased levels of SNO‐Hb are associated with lower tissue oxygenation.
Methods: A prospective cohort study of 63 adult Death by Neurological Criteria (DNC) organ donors was performed . Serial measurements of arterial S-nitroso-hemoglobin (SNO-Hb) were collected and tissue oxygenation (StO2) were continuously measured by a tissue oxygen monitor (T-STAT). The data was analyzed using R software.
Results: Brain death associated with variable SNO disturbance. SNO-Hb levels are highly positively correlated with tissue oxygenation with low SNO-HB correlating to low tissue oxygenation using best fit line analysis. (p<0.001) (R=0.61) The disruptions of SNO-Hb were also related to markers of injury and organ dysfunction.
Conclusion: Brain death is associated with 1) a variable decrease in SNO-HB and 2) decreasing levels of SNO-HB highly correlate with tissue hypoxia. Drug development targeting hemoglobin S‐nitrosylating agents that increase the supply of bioactive NO may provide a novel approach to improve VCA associated tissue hypoxia.
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