Predicting DCD Progression within 30 minutes: A Calculator to Assist Decisions to Implement Perfusion Strategies

S83 Poster Sessionswere compared using a Student's t-test with false discovery rate adjusted P values; correlation analysis was performed using a Pearson's correlation test.Results Reperfusion after ice storage compared to 10C demonstrated a shift towards anaerobic metabolism with accumulation of pyruvate precursors including lactate (P=0.023),phosphoenolpyruvate (P=0.023), and malate (P=0.030).For ice stored livers, there was a concurrent increase in dimethylmalonic acid (P=0.023), a competitive inhibitor of electron transport chain (ETC) enzyme succinate dehydrogenase.Increased abundance of dimethylmalonic acid corresponded to increased abundance of lactate (r=0.89,P=0.0005) and phosphoenolpyruvate (r=0.93,P<0.0001), demonstrating an association between ETC dysfunction and impaired aerobic respiration.(Figure 1) Compared to 10C, reperfusion after ice storage yielded increased metabolites of nucleic acid breakdown: hypoxanthine (P=0.023),guanine (P=0.026),cytosine (P=0.023),dCMP (0.023), dihydrouracil (P=0.023), and ribose (P=0.029).DNA fragmentation evaluated histologically through TUNEL staining demonstrated greater TUNEL + cells in ice compared to 10C livers after reperfusion: 23451 cells/hpf vs. 10539 cells/hpf, P=0.008.Metabolites of nucleotide breakdown correlated with TUNEL staining as a marker of DNA injury: hypoxanthine (r=0.65,P=0.041), guanine (r=0.79,P=0.006), and cytosine (r=0.71,P=0.02).(Figure 2) Conclusion Metabolomic analysis revealed patterns of impaired aerobic respiration, ETC dysfunction, and DNA injury after reperfusion of porcine DCD livers stored on ice compared to 10C.Static storage at 10C is a simple technique readily translatable to clinical practice that may mitigate IRI, particularly in donor organs most vulnerable.

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Publication Details

Journal
American Journal of Transplantation
Published
2025-01-01
DOI
https://doi.org/10.1016/j.ajt.2024.12.161
Primary Topic
Healthcare Policy and Management
Type
article
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article

Predicting DCD Progression within 30 minutes: A Calculator to Assist Decisions to Implement Perfusion Strategies

Trevor L. Nydam, Yanik J. Bababekov, Anna H. Ha, Bruce Kaplan et al.
American Journal of Transplantation
Healthcare Policy and Management
article

Predicting DCD Progression within 30 minutes: A Calculator to Assist Decisions to Implement Perfusion Strategies

Trevor L. Nydam, Yanik J. Bababekov, Anna H. Ha, Bruce Kaplan, John Malamon, Elizabeth A. Pomfret, Rashikh A. Choudhury, James J. Pomposelli, Arthur Yule, Jordan Hoffman, Carlos Gonçalves
article en

Abstract

S83 Poster Sessionswere compared using a Student's t-test with false discovery rate adjusted P values; correlation analysis was performed using a Pearson's correlation test.Results Reperfusion after ice storage compared to 10C demonstrated a shift towards anaerobic metabolism with accumulation of pyruvate precursors including lactate (P=0.023),phosphoenolpyruvate (P=0.023), and malate (P=0.030).For ice stored livers, there was a concurrent increase in dimethylmalonic acid (P=0.023), a competitive inhibitor of electron transport chain (ETC) enzyme succinate dehydrogenase.Increased abundance of dimethylmalonic acid corresponded to increased abundance of lactate (r=0.89,P=0.0005) and phosphoenolpyruvate (r=0.93,P<0.0001), demonstrating an association between ETC dysfunction and impaired aerobic respiration.(Figure 1) Compared to 10C, reperfusion after ice storage yielded increased metabolites of nucleic acid breakdown: hypoxanthine (P=0.023),guanine (P=0.026),cytosine (P=0.023),dCMP (0.023), dihydrouracil (P=0.023), and ribose (P=0.029).DNA fragmentation evaluated histologically through TUNEL staining demonstrated greater TUNEL + cells in ice compared to 10C livers after reperfusion: 23451 cells/hpf vs. 10539 cells/hpf, P=0.008.Metabolites of nucleotide breakdown correlated with TUNEL staining as a marker of DNA injury: hypoxanthine (r=0.65,P=0.041), guanine (r=0.79,P=0.006), and cytosine (r=0.71,P=0.02).(Figure 2) Conclusion Metabolomic analysis revealed patterns of impaired aerobic respiration, ETC dysfunction, and DNA injury after reperfusion of porcine DCD livers stored on ice compared to 10C.Static storage at 10C is a simple technique readily translatable to clinical practice that may mitigate IRI, particularly in donor organs most vulnerable.

American Journal of TransplantationVol. 25(1)
University of Colorado Hospital (US), University of Colorado Denver (US)
Openalex Percentile: Top 99%
Healthcare Policy and Management
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