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Investigating S-Nitrolysation (SNO) as a Possible Therapy to Enhance Tissue Perfusion in VCA Donors: A Study on Human Brain Death Donor SNO Mediated Tissue Perfusion
Mohamed Awad MD1, Anil Chaturvedi MS1, Samuel Boas BS1, Arvin Smith BS1, James Reynolds PhD2, Anand Kumar MD1
1 University Hospitals, Department of Plastic Surgery, Cleveland, OH
2 Case Western Reserve Univers
2020-02-15
Presenter: Mohamed Awad
Affidavit:
Mohamed Awad
Director Name: Mohamed Awad
Author Category: Medical Student
Presentation Category: Clinical
Abstract Category: General Reconstruction
Introduction: Tissue ischemia and 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. SNOs improve blood flow and oxygen delivery in the microcirculation and are thus a novel therapeutic target for the treatment of brain death related 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) was continuously measured by a tissue oxygen monitor (T-STAT). Data analysis was performed using R statistical software.
Results: Brain death was found to be associated with variable SNO disturbance. SNO-Hb levels were 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.
