An Unexpected Partnership: Alexis Carrel, Charles Lindbergh, and Normothermic Machine Perfusion.

Organ transplantation is a triumph of modern medicine which represents a culmination of science and imagination, saving thousands of lives a year. However, transplantation is severely limited by suitable donor allografts. To expand the donor pool and make transplantation achievable for all, normothermic machine perfusion (NMP) is being employed more frequently. Normothermic machine perfusion involves the utilization of a device to approximate the physiology of the human body, preserve organs outside of the donor, and provide a dynamic assessment platform to determine organ suitability for transplantation. As NMP technology advances, it will soon be possible to genetically modify and actively repair these organs. Although its application to the field of transplantation is relatively new, the concept, foundation, and development of NMP can be traced back to the pioneering work of the surgeon-scientist, Alexis Carrel and the famous aviator, Charles Lindbergh in the 1930s. Their collaboration resulted in the Carrel-Lindbergh Perfusion device, an early perfusion device that was able to keep organs alive ex vivo for weeks and is most appropriately viewed as a precursor to modern machine perfusion technologies. As NMP technology becomes more advanced and refined, it is important to acknowledge the historical context in which these technologies emerged.

Is Time Scheduling Important? An Analysis of Donor Heart Cross-clamp Times During Heart Transplantation.

Background: Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. Methods: A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results: Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P < 0.001). On unadjusted analysis, the survival difference among the 5 groups was insignificant (P = 0.07). Following adjustment, the periods of 11 am to 5 pm (HR: 1.09, 95% CI, 1.02-1.17; P = 0.012), 5 pm to 10 pm (HR: 1.11; 95% CI, 1.04-1.19; P = 0.002), and 10 pm to 4 am (HR: 1.07; 95% CI, 1.01-1.15; P = 0.034), were all independently associated with increased long-term mortality. Notably, the time of 8 am to 11 am was not associated with a change in survival (HR: 1.04; 95% CI, 0.96-1.14; P = 0.3). Conclusions: Given the independent association of donor timing and survival after adjustment in a large national cohort, further investigation into the role of donor circadian rhythm and donor procurement time is warranted in preclinical and clinical studies. Understanding the underlying mechanisms of this observation could potentially lead to the development of effective treatments and donor procurement processes that prepare the organs for transplantation in a better condition.

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Does Size Matter? The Effect of Size of Distal Perfusion Catheter on Acute Limb Ischemia: A Meta-Analysis.

Prevention of limb ischemia in patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is primarily achieved through the use of distal perfusion catheters (DPC). Our objective was to assess the role of DPC, and specifically the size of the catheter, in reducing the incidence of acute limb ischemia (ALI) through a meta-analysis. Seventeen studies met criteria for analysis. Pooled analysis included a total of 2,040 patients, of which 904 patients received ECMO with DPC and 1,136 patients underwent ECMO without DPC. Compared with ECMO alone, ECMO with DPC, regardless of size, significantly decreased ALI (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.31-0.77; p = 0.002). When comparing reactive versus prophylactic placement of DPC, prophylactic DPC was associated with significantly decreased ALI (RR: 0.41, 95% CI: 0.24-0.71; p = 0.02). No differences in mortality (RR: 0.89, 95% CI: 0.76-1.03; p = 0.12) and bleeding events (RR: 1.43, 95% CI: 0.41-4.96; p = 0.58) were observed between the two groups. This analysis demonstrates that the placement of DPC, if done prophylactically and regardless of size, is associated with a reduced risk of ALI versus the absence of DPC placement, but is not associated with differences in mortality or bleeding events.

Polymerized Human Hemoglobin-Based Oxygen Carrier Preserves Lung Allograft Function During Normothermic Ex Vivo Lung Perfusion.

Normothermic ex vivo lung perfusion (EVLP) can resuscitate marginal lung allografts to increase organs available for transplantation. During normothermic perfusion, cellular metabolism is more active compared with subnormothermic perfusion, creating a need for an oxygen (O2) carrier in the perfusate. As an O2 carrier, red blood cells (RBCs) are a scarce resource and are susceptible to hemolysis in perfusion circuits, thus releasing cell-free hemoglobin (Hb), which can extravasate into the tissue space, thus promoting scavenging of nitric oxide (NO) and oxidative tissue damage. Fortunately, polymerized human Hb (PolyhHb) represents a synthetic O2 carrier with a larger molecular diameter compared with Hb, preventing extravasation, and limiting adverse reactions. In this study, a next-generation PolyhHb-based perfusate was compared to both RBC and asanguinous perfusates in a rat EVLP model. During EVLP, the pulmonary arterial pressure and pulmonary vascular resistance were both significantly higher in lungs perfused with RBCs, which is consistent with RBC hemolysis. Lungs perfused with PolyhHb demonstrated greater oxygenation than those perfused with RBCs. Post-EVLP analysis revealed that the PolyhHb perfusate elicited less cellular damage, extravasation, iron tissue deposition, and edema than either RBCs or colloid control. These results show promise for a next-generation PolyhHb to maintain lung function throughout EVLP.

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation.

INTRODUCTION: Primary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. METHODS: LT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. RESULTS: The PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. CONCLUSIONS: While PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Textbook outcome: A novel metric in heart transplantation outcomes.

OBJECTIVE: Assessing heart transplant program quality using short-term survival is insufficient. We define and validate the composite metric textbook outcome and examine its association with overall survival. METHODS: We identified all primary, isolated adult heart transplants in the United Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files from May 1, 2005, to December 31, 2017. Textbook outcome was defined as length of stay 30 days or less; ejection fraction greater than 50% during 1-year follow-up; functional status 80% to 100% at 1 year; freedom from acute rejection, dialysis, and stroke during the index hospitalization; and freedom from graft failure, dialysis, rejection, retransplantation, and mortality during the first year post-transplant. Univariate and multivariate analyses were performed. Factors independently associated with textbook outcome were used to create a predictive nomogram. Conditional survival at 1 year was measured. RESULTS: A total of 24,620 patients were identified with 11,169 (45.4%, 95% confidence interval, 44.7-46.0) experiencing textbook outcome. Patients with textbook outcome were more likely free from preoperative mechanical support (odds ratio, 3.504, 95% confidence interval, 2.766 to 4.439, P < .001), free from preoperative dialysis (odds ratio, 2.295, 95% confidence interval, 1.868-2.819, P < .001), to be not hospitalized (odds ratio, 1.264, 95% confidence interval, 1.183-1.349, P < .001), to be nondiabetic (odds ratio, 1.187, 95% confidence interval, 1.113-1.266, P < .001), and to be nonsmokers (odds ratio, 1.160, 95% confidence interval,1.097-1.228, P < .001). Patients with textbook outcome have improved long-term survival relative to patients without textbook outcome who survive at least 1 year (hazard ratio for death, 0.547, 95% confidence interval, 0.504-0.593, P < .001). CONCLUSIONS: Textbook outcome is an alternative means of examining heart transplant outcomes and is associated with long-term survival. The use of textbook outcome as an adjunctive metric provides a holistic view of patient and center outcomes.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

Mitsugumin 53 mitigation of ischemia-reperfusion injury in a mouse model.

OBJECTIVE: Primary graft dysfunction is often attributed to ischemia-reperfusion injury, and prevention would be a therapeutic approach to mitigate injury. Mitsugumin 53, a myokine, is a component of the endogenous cell membrane repair machinery. Previously, exogenous administration of recombinant human (recombinant human mitsugumin 53) protein has been shown to mitigate acute lung injury. In this study, we aimed to quantify a therapeutic benefit of recombinant human mitsugumin 53 to mitigate a transplant-relevant model of ischemia-reperfusion injury. METHODS: C57BL/6J mice were subjected to 1 hour of ischemia (via left lung hilar clamp), followed by 24 hours of reperfusion. mg53-/- mice were administered exogenous recombinant human mitsugumin 53 or saline before reperfusion. Tissue, bronchoalveolar lavage, and blood samples were collected at death and used to quantify the extent of lung injury via histology and biochemical assays. RESULTS: Administration of recombinant human mitsugumin 53 showed a significant decrease in an established biometric profile of lung injury as measured by lactate dehydrogenase and endothelin-1 in the bronchoalveolar lavage and plasma. Biochemical markers of apoptosis and pyroptosis (interleukin-1ß and tumor necrosis factor-α) were also significantly mitigated, overall demonstrating recombinant human mitsugumin 53's ability to decrease the inflammatory response of ischemia-reperfusion injury. Exogenous recombinant human mitsugumin 53 administration showed a trend toward decreasing overall cellular infiltrate and neutrophil response. Fluorescent colocalization imaging revealed recombinant human mitsugumin 53 was effectively delivered to the endothelium. CONCLUSIONS: These data demonstrate that recombinant human mitsugumin 53 has the potential to prevent or reverse ischemia-reperfusion injury-mediated lung damage. Although additional studies are needed in wild-type mice to demonstrate efficacy, this work serves as proof-of-concept to indicate the potential therapeutic benefit of mitsugumin 53 administration to mitigate ischemia-reperfusion injury.

Monitored Anesthesia Care for Axillary Impella 5.5 Placement: A Feasible Option for Patients With Severe Cardiogenic Shock With Relative Contraindication to Intubation.

The Impella 5.5 left ventricular assist device (LVAD) is typically placed in a hybrid operating room with fluoroscopic and echocardiographic guidance under general anesthesia. In this case report, we describe a patient with severe cardiopulmonary failure necessitating an Impella 5.5 as a bridge to heart/lung transplant. Here, we describe the successful placement of the Impella 5.5 with sedation and local anesthesia in order to avoid general anesthesia and the sequelae of positive pressure ventilation in a fragile patient. Impella placement was confirmed with transesophageal echocardiography. This case report demonstrates a novel strategy for placing the Impella 5.5 and, more importantly, opens the possibility to future prospective studies of this technique.

MG53 mitigates warm ischemic lung injury in a murine model of transplantation.

OBJECTIVES: Lung transplant warm ischemia-reperfusion injury (IRI) results in cellular injury, inflammation, and poor graft function. Mitsugumin 53 (MG53) is an endogenous protein with cell membrane repair properties and the ability to modulate the inflammasome. We hypothesize that the absence of circulating MG53 protein in the recipient increases IRI, and higher levels of circulating MG53 protein mitigate IRI associated with lung transplantation. METHODS: To demonstrate protection, wild-type (wt) lung donor allografts were transplanted into a wt background, a MG53 knockout (mg53-/-), or a constitutively overexpressed MG53 (tissue plasminogen activator-MG53) recipient mouse after 1 hour of warm ischemic injury. Mice survived for 5 days after transplantation. Bronchioalveolar lavage, serum, and tissue were collected at sacrifice. Bronchioalveolar lavage, serum, and tissue markers of apoptosis and a biometric profile of lung health were analyzed. RESULTS: mg53-/- mice had significantly greater levels of markers of overall cell lysis and endothelial cell injury. Overexpression of MG53 resulted in a signature similar to that of wt controls. At the time of explant, tissue plasminogen activator-MG53 recipient tissue expressed significantly greater levels of MG53, measured by immunohistochemistry, compared with mg53-/-, demonstrating uptake of endogenous overexpressed MG53 into donor tissue. CONCLUSIONS: In a warm IRI model of lung transplantation, the absence of MG53 resulted in increased cell injury and inflammation. Endogenous overexpression of MG53 in the recipient results in protection in the wt donor. Together, these data suggest that MG53 is a potential therapeutic agent for use in lung transplantation to mitigate IRI.

The role of CD38 in ischemia reperfusion injury in cardiopulmonary bypass and thoracic transplantation: a narrative review.

Background and Objective: Ischemia reperfusion injury (IRI) is often the underlying cause of endothelium breakdown and damage in cardiac or transplantation operations, which can lead to disastrous post-operative consequences. Recent studies of cluster of differentiation 38 (CD38) have identified its critical role in IRI. Our objective is to provide a comprehensive overview of CD38-mediated axis, pathways, and potential CD38 translational therapies for reducing inflammation associated with cardiopulmonary bypass (CPB) or thoracic transplantation and IRI. Methods: We conducted a review of the literature by performing a search of the PubMed database on 2 April 2023. To find relevant publications on CD38, we utilized the MeSH terms: "CD38" AND "Ischemia" OR "CD38" AND "Transplant" OR "CD38" AND "Heart" from 1990-2023. Additional papers were included if they were felt to be relevant but were not captured in the MeSH terms. We found 160 papers that met this criterion, and following screening, exclusion and consensus a total of 36 papers were included. Key Content and Findings: CD38 is most notably a nicotine adenine dinucleotide (NAD)+ glycohydrolase (NADase), and a generator of Ca2+ signaling secondary messengers. Ultimately, the release of these secondary messengers leads to the activation of important mediators of cellular death. In the heart and during thoracic transplantation, this pathway is intimately involved in a wide variety of injuries; namely the endothelium. In the heart, activation generally results in vasoconstriction, poor myocardial perfusion, and ultimately poor cardiac function. CD38 activation also prevents the accumulation of atherosclerotic disease. During transplantation, intracellular activation leads to infiltration of recipient innate immune cells, tissue edema, and ultimately primary graft dysfunction (PGD). Specifically, in heart transplantation, extracellular activation could be protective and improve allograft survival. Conclusions: The knowledge gap in understanding the molecular basis of IRI has prevented further development of novel therapies and treatments. The possible interaction of CD38 with CD39 in the endothelium, and the modulation of the CD38 axis may be a pathway to improve cardiovascular outcomes, heart and lung donor organ quality, and overall longevity.

Successful Orthotopic Liver Transplantation in Mice Utilizing Microcomputed Tomography Angiography.

Microcomputed tomography (microCT) angiography is an invaluable resource to researchers. New advances in this technology have allowed for high-quality images to be obtained of micro-vasculature and are high-fidelity tools in the field of organ transplantation. In this model of orthotopic liver transplantation (OLT) in mice, microCT affords the opportunity to evaluate allograft anastomosis in real time and has the added benefit of not having to sacrifice study animals. The choice of contrast, as well as image acquisition settings, create a high-definition image, which gives researchers invaluable information. This allows for evaluation of the technical aspects of the procedure as well as potentially evaluating different therapeutics over an extended duration of time. In this protocol, we detail an OLT model in mice in a stepwise fashion and finally describe a microCT protocol that can give high-quality images, which aid researchers in in-depth analysis of solid organ transplantation. We provide a step-by-step guide for liver transplantation in a mouse, as well as briefly discuss a protocol for evaluating the patency of the graft through microCT angiography.

XPS™ Jensen lung as a low-cost, high-fidelity training adjunct to ex-vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) enables lung resuscitation before transplantation, and training is key, particularly in low-volume settings. To enable technique refinement and continuing education, we sought to demonstrate the value of a low-cost, high-fidelity EVLP simulator that would allow reproducible clinical scenarios. METHODS: In partnership with our EVLP manufacturer, we utilized the XPS™ Jensen Lung with our clinical system. The Jensen Lung has two simulated lung bladders and an in-line polymethylpentene fiber oxygenator. It allows titration of ventilator support which aids in accurate clinical simulation. For simulations, blood gases (BGs) were obtained and compared with integrated in-line perfusate gas monitors (PGMs). PaO2 , PCO2 , and pH were measured and compared. RESULTS: The PGM and BG values were not significantly different throughout the range of FiO2 and sweep gas flow rates evaluated. The "delta" PaO2 was measured between LA and PA and did not show any change between approaches. The pH measurement between BG and PGM was not significantly different. CONCLUSIONS: The XPS™ Jensen Lung simulator allows for a high-fidelity simulator of clinical EVLP. The correlation of the PGM and the BG measurement of the PaO2 and pH allow for a low-cost simulation, as the PGMs are in line in the circuit, and enable real-time tracking of perfusate gas parameters with the PGM. Implementation of a standardized clinical EVLP training program allows the maintenance of technique and enables clinical simulation training without the need for costly animal perfusions and the use of multiple BG measurements.

Biometric Profiling to Quantify Lung Injury Through Ex Vivo Lung Perfusion Following Warm Ischemia.

Standard physiologic assessment parameters of donor lung grafts may not accurately reflect lung injury or quality. A biometric profile of ischemic injury could be identified as a means to assess the quality of the donor allograft. We sought to identify a biometric profile of lung ischemic injury assessed during ex vivo lung perfusion (EVLP). A rat model of lung donation after circulatory death (DCD) warm ischemic injury with subsequent EVLP evaluation was utilized. We did not observe a significant correlation between the classical physiological assessment parameters and the duration of the ischemic. In the perfusate, solubilized lactate dehydrogenase (LDH) as well as hyaluronic acid (HA) significantly correlated with duration of ischemic injury and length of perfusion ( p < 0.05). Similarly, in perfusates, the endothelin-1 (ET-1) and Big ET-1 correlated ischemic injury ( p < 0.05) and demonstrated a measure of endothelial cell injury. In tissue protein expression, heme oxygenase-1 (HO-1), angiopoietin 1 (Ang-1), and angiopoietin 2 (Ang-2) levels were correlated with the duration of ischemic injury ( p < 0.05). Cleaved caspase-3 levels were significantly elevated at 90 and 120 minutes ( p < 0.05) demonstrating increased apoptosis. A biometric profile of solubilized and tissue protein markers correlated with cell injury is a critical tool to aid in the evaluation of lung transplantation, as accurate evaluation of lung quality is imperative and improved quality leads to better results. http://links.lww.com/ASAIO/B49.