Browsing by Author "Gao, Qimeng"

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    Donor Leukocyte Trafficking and Damage-associated Molecular Pattern Expression During Ex Vivo Lung Perfusion.
    (Transplantation Direct, 2020-03) Davis, Robert P; Yerxa, John; Gao, Qimeng; Gloria, Jared; Scheuermann, Uwe; Song, Mingqing; Zhang, Min; Parker, William; Lee, Jaewoo; Hartwig, Matthew G; Barbas, Andrew S
    Background:While ex vivo lung perfusion (EVLP) has become established in lung transplantation, the cellular processes occurring during this period are not yet fully understood. Prior studies demonstrated that donor leukocytes (DLs) migrate from the graft into the perfusate during EVLP, but the distribution of DLs in graft and perfusate compartments has not been characterized. Moreover, cell death of DLs has been implicated in mediating graft injury during EVLP, but the underlying mechanisms have not been elucidated. We hypothesized the following: (1) there is a nonspecific migration of DLs from the graft into perfusate and (2) cell death of DLs releases damage-associated molecular patterns (DAMPs) that contribute to the inflammatory milieu during EVLP. Methods:EVLP was performed on rat lungs for 3 hours (N = 6). At the end of EVLP, flow cytometry was used to quantify the distribution of different DL cell types in both the graft and perfusate compartments. During EVLP, the perfusate was also sampled hourly to measure levels of DAMPs and downstream inflammatory cytokines generated during EVLP. Results:At the conclusion of EVLP, there was a significantly higher proportion of T and B cells present in the perfusate compartment compared with the graft compartment. There was a time-dependent increase in extracellular DNA and tumor necrosis factor α in the perfusate during EVLP. Conclusions:T cells and B cells are enriched in the perfusate compartment during EVLP. Cell death of DLs contributes to an accumulation of DAMPs during EVLP.
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    Incidence of Postreperfusion Hyperfibrinolysis in Liver Transplantation by Donor Type and Observed Treatment Strategies.
    (Anesthesia and analgesia, 2023-03) Krom, Russell J; Welsby, Ian J; Fuller, Matthew; Barbas, Andrew S; Gao, Qimeng; Anwar, Imran J; Dunkman, W Jonathan

    Background

    Hyperfibrinolysis is a possible complication during liver transplantation, particularly immediately after reperfusion.

    Methods

    We performed a retrospective study to examine the incidence, treatment, and resolution of postreperfusion hyperfibrinolysis in patients undergoing liver transplantation at Duke University Hospital from 2015 to 2020.

    Results

    Out of 535 patients undergoing liver transplantation, 21 or 3.9%, 95% CI (2.5-5.9), had hyperfibrinolysis after reperfusion. Hyperfibrinolysis occurred in 16 of 511 (3.1%) patients receiving livers from DBD donors, 5 of 18 (27.8%) patients receiving livers from donation after circulatory death (DCD) donors, and 0 of 6 (0.0%) patients receiving livers from living donors. Fibrinolysis was treated with cryoprecipitate (12/21), a combination of cryoprecipitate and tranexamic acid (3/21), or neither (6/21) and resolved within several hours in all cases.

    Conclusions

    Anesthesiologists should be aware of the possibility of postreperfusion hyperfibrinolysis in liver transplantation, particularly with DCD donors, and may consider treatment with cryoprecipitate or tranexamic acid. Further work is needed to identify any potential differences, such as faster resolution of fibrinolysis, between different treatment modalities.
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    Kidney Donor Profile Index Is a Reliable Alternative to Liver Donor Risk Index in Quantifying Graft Quality in Liver Transplantation.
    (Transplantation direct, 2019-12) Scheuermann, Uwe; Truong, Tracy; Seyferth, Elisabeth R; Freischlag, Kyle; Gao, Qimeng; Yerxa, John; Ezekian, Brian; Davis, Robert P; Schroder, Paul M; Peskoe, Sarah B; Barbas, Andrew S
    Background:The most established metric for estimating graft survival from donor characteristics in liver transplantation is the liver donor risk index (LDRI). The LDRI is calculated from donor and transplant-related variables, including cold ischemic time. Because cold ischemic time is unknown at the time of organ offer, LDRI is not available for organ acceptance decisions. In contrast, the kidney donor profile index (KDPI) is derived purely from donor variables known at the time of offer and thus calculated for every deceased donor in the United States. The similarity in donor factors included in LDRI and KDPI led us to hypothesize that KDPI would reliably approximate LDRI in estimating graft survival in liver transplantation. Methods:The United Network of Organ Sharing registry was queried for adults who underwent deceased donor liver transplantation from 2002 to 2016. The cohort was divided into quintiles of KDPI and LDRI, and graft survival was calculated according to Kaplan Meier. Hazard ratios for LDRI and KDPI were estimated from Cox proportional hazards models, and Uno's concordance statistic was compared. Results:In our analysis of 63 906 cases, KDPI closely approximated LDRI in estimating liver graft survival, with an equivalent concordance statistic of 0.56. Conclusions:We conclude that KDPI can serve as a reasonable alternative to LDRI in liver acceptance decisions.
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    Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion.
    (Transplantation direct, 2022-11) Abraham, Nader; Ludwig, Elsa K; Schaaf, Cecilia R; Veerasammy, Brittany; Stewart, Amy S; McKinney, Caroline; Freund, John; Brassil, John; Samy, Kannan P; Gao, Qimeng; Kahan, Riley; Niedzwiecki, Donna; Cardona, Diana M; Garman, Katherine S; Barbas, Andrew S; Sudan, Debra L; Gonzalez, Liara M
    Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model.

    Methods

    Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice.

    Results

    In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function.

    Conclusions

    This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.