National trends and outcomes of heart-kidney transplantation using hepatitis C positive donors.

BACKGROUND: This study evaluated the outcomes of combined heart-kidney transplantation in the United States using hepatitis C positive (HCV+) donors. METHODS: Adults undergoing combined heart-kidney transplantation from 2015 to 2020 were identified in the United Network for Organ Sharing registry. Patients were stratified by donor HCV status. Kaplan-Meier curves with multivariable Cox regression models were used for risk-adjustment in a propensity-matched cohort. RESULTS: A total of 950 patients underwent heart-kidney transplantation of which 7.8% (n = 75) used HCV+ donors; 68% (n = 51) were viremic and 32% (n = 24) were non-viremic donors. Unadjusted 1-year recipient survival was similar between HCV+ versus HCV- donors (84% vs 88%, respectively; P = .33). Risk-adjusted analysis in the propensity-matched cohort showed HCV+ donor use did not confer increased risk of 1-year mortality (hazard ratio .63, 95% CI .17-2.32; P = .49). Sub-group analysis showed viremic and non-viremic HCV+ donors had similar 1-year survival as well (84% vs 84%; P = .95). CONCLUSIONS: Compared with recipients of HCV- donor dual heart-kidney transplants, recipients of HCV+ organs had comparable 1-year survival and clinical outcomes after combined transplantation. Although future studies should evaluate other outcomes related to HCV+ donor use, this practice appears safe and should be expanded further in the heart-kidney transplant population.

HVAD versus heartmate III bridge to heart transplantation: Waitlist and posttransplant outcomes.

BACKGROUND: This study compared outcomes of patients bridged with either the Heartware HVAD or Heartmate 3 (HM3) device to orthotopic heart transplantation (OHT). METHODS: The United Network of Organ Sharing registry was queried to perform two separate analyses of adult, isolated OHT candidates bridged with HVAD or HM3. First, waitlist outcomes were compared among patients waitlisted 1/1/2015-3/20/2020. Second, posttransplant survival was compared among those transplanted 1/1/2015-3/20/2020. RESULTS: Two thousand two hundred fifty-five candidates were waitlisted within the study period, 1587 (70.4%) bridged with HVAD and 668 (29.6%) with HM3. At 1 year from waitlisting, cumulative incidence of OHT higher in the HVAD cohort (p < .001). During the same time period, 2643 patients underwent OHT, 2154 (81.5%) with prior HVAD and 489 (18.5%) with HM3. Yearly proportions of patients bridged with HM3 increased across the study period and decreased for HVAD (p < .001). HM3-bridged recipients had shorter waitlist times, longer graft cold ischemic times, and experienced a higher rate of posttransplant dialysis requirement. Unadjusted and risk-adjusted posttransplant mortality rates were similar between both groups. CONCLUSIONS: Posttransplant survival is equivalent regardless of device type used for bridging. However, HM3 patients had lower likelihood of reaching transplantation, which may be a reflection of the recent heart allocation policy changes.

ZFP148 (Zinc-Finger Protein 148) Binds Cooperatively With NF-1 (Neurofibromin 1) to Inhibit Smooth Muscle Marker Gene Expression During Abdominal Aortic Aneurysm Formation.

Objective- The goal of this study was to determine the role of ZFP148 (zinc-finger protein 148) in aneurysm formation. Approach and Results- ZFP148 mRNA expression increased at day 3, 7, 14, 21, and 28 after during abdominal aortic aneurysm formation in C57BL/6 mice. Loss of ZFP148 conferred abdominal aortic aneurysm protection using ERTCre+ ZFP148 flx/flx mice. In a third set of experiments, smooth muscle-specific loss of ZFP148 alleles resulted in progressively greater protection using novel transgenic mice (MYH [myosin heavy chain 11] Cre+ flx/flx, flx/wt, and wt/wt). Elastin degradation, LGAL3, and neutrophil staining were significantly attenuated, while α-actin staining was increased in ZFP148 knockout mice. Results were verified in total cell ZFP148 and smooth muscle-specific knockout mice using an angiotensin II model. ZFP148 smooth muscle-specific conditional mice demonstrated increased proliferation and ZFP148 was shown to bind to the p21 promoter during abdominal aortic aneurysm formation. ZFP148 smooth muscle-specific conditional knockout mice also demonstrated decreased apoptosis as measured by decreased cleaved caspase-3 staining. ZFP148 bound smooth muscle marker genes via chromatin immunoprecipitation analysis mediated by NF-1 (neurofibromin 1) promote histone H3K4 deacetylation via histone deacetylase 5. Transient transfections and chromatin immunoprecipitation analyses demonstrated that NF-1 was required for ZFP148 protein binding to smooth muscle marker genes promoters during aneurysm formation. Elimination of NF-1 using shRNA approaches demonstrated that NF-1 is required for binding and elimination of NF-1 increased BRG1 recruitment, the ATPase subunit of the SWI/SWF complex, and increased histone acetylation. Conclusions- ZFP148 plays a critical role in multiple murine models of aneurysm formation. These results suggest that ZFP148 is important in the regulation of proliferation, smooth muscle gene downregulation, and apoptosis in aneurysm development.

D-series resolvins inhibit murine abdominal aortic aneurysm formation and increase M2 macrophage polarization.

The role of resolvins in abdominal aortic aneurysm (AAA) has not been established. We hypothesized that treatment with D-series resolvins (RvD2 or RvD1) would attenuate murine AAA formation through alterations in macrophage polarization and cytokine expression. Male C57/B6 mice (n = 9 per group) 8 to 12 wk old received RvD2 (100 ng/kg/treatment), RvD1 (100 ng/kg/treatment), or vehicle only every third day beginning 3 d before abdominal aortic perfusion with elastase as prevention. Aortas were collected 14 d after elastase perfusion. Cytokine analysis (n = 5 per group) or confocal microscopy (n = 4 per group) was performed. In a separate experiment, RvD2 was provided to mice with small AAAs 3 d after elastase treatment (n = 8 per group). Additionally, apolipoprotein E knockout mice treated with angiotensin II (1000 ng/kg) were treated with RvD2 or vehicle alone (n = 10 per group) in a nonsurgical model of AAA. To determine the effect of RvD2 on macrophage polarization, confocal staining for macrophages, M1 and M2 macrophage subtypes, α-actin, and DAPI was performed. Mean aortic dilation was 96 ± 13% for vehicle-treated mice, 57 ± 9.7% for RvD2-treated mice, and 61 ± 11% for RvD1-treated mice (P < 0.0001). Proinflammatory cytokines macrophage chemotactic protein 1, C-X-C motif ligand 1, and IL-1ß were significantly elevated in control animals compared to RvD2- and RvD1-treated animals (P < 0.05), resulting in a reduction of matrix metalloproteinase 2 and 9 activity in resolvin-treated mice in both elastase and angiotensin II models. Treatment of existing small AAAs with RvD2 demonstrated a 25% reduction in aneurysm size at d 14 compared to vehicle alone (P = 0.018). Confocal histology demonstrated a prevalence of M2 macrophages within the aortic medium in mice treated with RvD2. Resolvin D2 exhibits a potent protective effect against experimental AAA formation. Treatment with RvD2 significantly influences macrophage polarization and decreases several important proinflammatory cytokines. Resolvins and the alteration of macrophage polarization represent potential future targets for prevention of AAA.-Pope, N. H., Salmon, M., Davis, J. P., Chatterjee, A., Su, G., Conte, M. S., Ailawadi, G., Upchurch, G. R., Jr. D-series resolvins inhibit murine abdominal aortic aneurysm formation and increase M2 macrophage polarization.

Mesenchymal Stem Cells Attenuate NADPH Oxidase-Dependent High Mobility Group Box 1 Production and Inhibit Abdominal Aortic Aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation, and matrix degradation. This study tests the hypothesis that macrophage-produced high mobility group box 1 (HMGB1) production is dependent on nicotinamide adenine dinucleotide phosphate oxidase (Nox2), which leads to increase in interleukin (IL)-17 production resulting in AAA formation and that treatment with human mesenchymal stem cells (MSCs) can attenuate this process thereby inhibiting AAA formation. APPROACH AND RESULTS: Human aortic tissue demonstrated a significant increase in HMGB1 expression in AAA patients when compared with controls. An elastase-perfusion model of AAA demonstrated a significant increase in HMGB1 production in C57BL/6 (wild-type [WT]) mice, which was attenuated by MSC treatment. Furthermore, anti-HMGB1 antibody treatment of WT mice attenuated AAA formation, IL-17 production, and immune cell infiltration when compared with elastase-perfused WT mice on day 14. Elastase-perfused Nox2(-/y) mice demonstrated a significant attenuation of HMGB1 and IL-17 production, cellular infiltration, matrix metalloproteinase activity, and AAA formation when compared with WT mice on day 14. In vitro studies showed that elastase-treated macrophages from WT mice, but not from Nox2(-/y) mice, produced HMGB1, which was attenuated by MSC treatment. The production of macrophage-dependent HMGB1 involved Nox2 activation and superoxide anion production, which was mitigated by MSC treatment. CONCLUSIONS: These results demonstrate that macrophage-produced HMGB1 leads to aortic inflammation and acts as a trigger for CD4(+) T-cell-produced IL-17 during AAA formation. HMGB1 release is dependent on Nox2 activation, which can be inhibited by MSCs leading to attenuation of proinflammatory cytokines, especially IL-17, and protection against AAA formation.

Pharmacologic blockade and genetic deletion of androgen receptor attenuates aortic aneurysm formation.

BACKGROUND: Testosterone is theorized to play a major role in the pathophysiology of abdominal aortic aneurysms (AAAs) because this disease occurs primarily in men. The role of the androgen receptor (AR) in the formation of AAAs has not been well elucidated, and therefore, it is hypothesized that androgen blockade will attenuate experimental aortic aneurysm formation. METHODS: Aortas of 8- to 12-week-old male C57Bl/6 wild-type (WT) mice or male AR knockout (AR(-/-)) mice were perfused with purified porcine pancreatic elastase (0.35 U/mL) to induce AAA formation. Two groups of WT male mice were treated with the AR blockers flutamide (50 mg/kg) or ketoconazole (150 mg/kg) twice daily by intraperitoneal injection. Aortas were harvested on day 14 after video micrometry was used to measure AAA diameter. Cytokine arrays and histologic analysis were performed on aortic tissue. Groups were compared using an analysis of variance and a Tukey post hoc test. RESULTS: Flutamide and ketoconazole treatment (mean ± standard error of the mean) attenuated AAA formation in WT mice (84.2% ± 22.8% [P = .009] and 91.5% ± 18.2% [P = .037]) compared with WT elastase (121% ± 5.23%). In addition, AR(-/-) mice showed attenuation of AAA growth (64.4% ± 22.7%; P < .0001) compared with WT elastase. Cytokine arrays of aortic tissue revealed decreased levels of proinflammatory cytokines interleukin (IL)-α, IL-6, and IL-17 in flutamide-treated and AR(-/-) groups compared with controls. CONCLUSIONS: Pharmacologic and genetic AR blockade cause attenuation of AAA formation. Therapies for AR blockade used in prostate cancer may provide medical treatment to halt progression of AAAs in humans.

Inhibition of interleukin-1ß decreases aneurysm formation and progression in a novel model of thoracic aortic aneurysms.

BACKGROUND: Thoracic aortic aneurysms (TAAs) are common, but experimental TAA models are limited and the role of interleukin-1ß (IL-1ß) is undetermined. METHODS AND RESULTS: IL-1ß protein was measured in human TAAs and control aortas, and IL-1ß protein was increased ≈20-fold in human TAAs. To develop an experimental model of TAAs, 8- to 10-week-old male C57Bl/6 mice (wild type [WT]) underwent thoracotomy with application of periadventitial elastase (WT TAA) or saline (WT control; n=30 per group). Elastase treatment to thoracic aortas resulted in progressive dilation until day 14 with maximal dilation of 99.6±24.7% compared with 14.4±8.2% for WT saline control (P<0.0001). WT TAAs demonstrated elastin fragmentation, smooth muscle cell loss, macrophage infiltration, and increased IL-1ß expression. Next, TAAs were induced in mice deficient of IL-1ß (IL-1ß knockout) or IL-1 receptor (IL-1R knockout; n=10 each). Genetic deletion of IL-1ß and IL-1R significantly decreased thoracic aortic dilation (IL-1ß knockout=54.2±16.8% and IL-1R knockout=62.6±17.2% versus WT TAA=104.7±23.8%; P<0.001for both). IL-1ß knockout and IL-1R knockout aortas demonstrated preserved elastin and smooth muscle cells with fewer inflammatory cells. Correspondingly, IL-1ß and IL-1R knockout aortas had decreased inflammatory cytokine and matrix metalloproteinase 9 expression. Separately, WT mice pretreated with either IL-1R antagonist anakinra (100 mg/kg per day) or vehicle alone (control) underwent elastase treatment. Pretreatment of WT mice with anakinra attenuated TAA formation (control: 99.2±15.5% versus anakinra: 68.3±19.2%; P<0.005). Finally, to investigate treatment of small TAAs, WT mice were treated with anakinra 3 days after TAA induction. Anakinra treatment in WT mice with small TAAs reduced aortic dilation on day 14 (control treatment: 89.1±18.6% versus anakinra treatment: 59.7±25.7%; P=0.01). CONCLUSIONS: Periadventitial application of elastase to murine thoracic aortas reproducibly produced aneurysms with molecular and histological features consistent with TAA disease. Genetic and pharmacological inhibition of IL-1ß decreased TAA formation and progression, indicating that IL-1ß may be a potential target for TAA treatment.

B2 cells suppress experimental abdominal aortic aneurysms.

Recent reports of rupture in patients with abdominal aortic aneurysm (AAA) receiving B-cell depletion therapy highlight the importance of understanding the role of B cells (B1 and B2 subsets) in the development of AAA. We hypothesized that B2 cells aggravate experimental aneurysm formation. The IHC staining revealed infiltration of B cells in the aorta of wild-type (C57BL/6) mice at day 7 after elastase perfusion and persisted through day 21. Quantification of immune cell types using flow cytometry at day 14 showed significantly greater infiltration of mononuclear cells, including B cells (B2: 93% of total B cells) and T cells in elastase-perfused aortas compared with saline-perfused or normal aortas. muMT (mature B-cell deficient) mice were prone to AAA formation similar to wild-type mice in two different experimental AAA models. Contradicting our hypothesis, adoptive transfer of B2 cells suppressed AAA formation (102.0% ± 7.3% versus 75.2% ± 5.5%; P < 0.05) with concomitant increase in the splenic regulatory T cell (0.24% ± 0.03% versus 0.92% ± 0.23%; P < 0.05) and decrease in aortic infiltration of mononuclear cells. Our data suggest that B2 cells constitute the largest population of B cells in experimental AAA. Furthermore, B2 cells, in the absence of other B-cell subsets, increase splenic regulatory T-cell population and suppress AAA formation.

Attenuation of aortic aneurysms with stem cells from different genders.

BACKGROUND: No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC. MATERIALS AND METHODS: Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 µL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. RESULTS: Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1ß, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). CONCLUSIONS: These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans.

KLF4 regulates abdominal aortic aneurysm morphology and deletion attenuates aneurysm formation.

BACKGROUND: KLF4 mediates inflammatory responses after vascular injury/disease; however, the role of KLF4 in abdominal aortic aneurysms (AAAs) remains unknown. The goals of the present study were to (1) determine the role of KLF4 in experimental AAA; and (2) determine the effect of KLF4 on smooth muscle (SM) cells in AAAs. METHODS AND RESULTS: KLF4 expression progressively increased at days 3, 7, and 14 after aortic elastase perfusion in C57BL/6 mice. Separately, loss of a KLF4 allele conferred AAA protection using ERTCre+ KLF4 flx/wt mice in the elastase AAA model. In a third set of experiments, SM-specific loss of 1 and 2 KLF4 alleles resulted in progressively greater protection using novel transgenic mice (MYHCre+ flx/flx, flx/wt, and wt/wt) in the elastase AAA model compared with control. Elastin degradation, MAC2, and cytokine production (MCP1, tumor necrosis factor-α, and interleukin-23) were significantly attenuated, whereas α-actin staining was increased in KLF4 knockout mice versus controls. Results were verified in global KLF4 and SM-specific knockout mice using an angiotensin II model of aneurysm formation. KLF4 inhibition with siRNA attenuated downregulation of SM gene expression in vitro, whereas in vivo studies demonstrated that KLF4 binds to promoters of SM genes by chromatin immunoprecipitation analysis. Finally, human aortic aneurysms demonstrated significantly higher KLF4 expression that was localized to SM cells. CONCLUSIONS: KLF4 plays a critical role in aortic aneurysm formation via effects on SM cells. These results suggest that KLF4 regulates SM cell phenotypic switching and could be a potential therapeutic target for AAA disease.

Prolonged Ischemia Times for Heart Transplantation: Impact of the 2018 Allocation Change.

BACKGROUND: In 2018, the United Network for Organ Sharing implemented a change in heart allocation policy resulting in increased organ ischemia times in early analyses. This study evaluated the effect of ischemia time on 1-year mortality in the context of allocation policy changes implemented in 2006 and 2018. METHODS: The United Network for Organ Sharing registry was used to identify adults undergoing heart transplantation from 2000 to 2020. Patients were stratified by the allocation policy era in which they received a transplant (2000-June 2006, July 2006-October 2018, October 2018-2020) and by ischemia time, defined as normal (≤4 hours) and prolonged (>4 hours). One-year survival was estimated using Kaplan-Meier analysis. Cox regression was used to determine risk-adjusted hazards for ischemia time on 1-year mortality. RESULTS: There were 40 052 patients included for analysis. Ischemia times were normal in 32 585 (81.36%) and prolonged in 7467 (18.64%) patients. The proportion of transplantations with prolonged ischemia times increased with each subsequent policy era. After the 2018 policy change, 1-year survival was 90.92% with normal ischemia times vs 87.52% with prolonged ischemia times (P < .001). Ischemia time independently predicted 1-year mortality in each era with a hazard ratio of 1.20 per hour (P = .004) in the current era. CONCLUSIONS: Prolonged ischemia times occur in a minority of cases but are increasing in frequency. The independent risk of prolonged ischemia time on 1-year mortality persists despite advances in storage technology and should remain a consideration in donor-recipient matching.

Heart Transplantation for Peripartum Cardiomyopathy: Outcomes Over 3 Decades.

BACKGROUND: This study evaluated trends and outcomes of patients undergoing heart transplantation for peripartum cardiomyopathy (PPCM) over the past 3 decades. METHODS: The United Network for Organ Sharing registry was used to identify patients undergoing isolated heart transplantation between 1987 and 2020. Patients were stratified by the decade of transplantation. Overall survival was compared using Kaplan-Meier analysis, and risk-adjustment was performed using Cox proportional hazards modeling. RESULTS: A total of 76 009 heart transplantations occurred in the study period, including 20 352 female patients and 809 female patients with PPCM. The frequency of transplantation for PPCM increased over the study period (P = .015). Among female patients, PPCM was significantly associated with 1-year mortality compared with nonischemic cardiomyopathy (hazard ratio, 1.38; 95% CI, 1.11-1.69; P = .004). Among patients with PPCM, Black and Hispanic heart transplant recipients had increased 1-year posttransplant mortality risk compared with White recipients. On Kaplan-Meier survival analysis, early and midterm survival was significantly worse in patients with PPCM compared with other female patients. The 5-, 10-, and 15-year survivals in patients with PPCM were 66.5%, 49.0%, and 40.2% compared with 74.3%, 56.0%, and 37.5% in female heart transplant recipients with other heart failure diagnoses, respectively (P < .001). Survival improved significantly in patients who underwent heart transplantation for PPCM in the latest decade from 2010 to 2020 compared with earlier decades (P < .001), and this improvement was most marked for Black recipients. CONCLUSIONS: Patients who underwent heart transplantation for PPCM have a significantly elevated risk for 1-year mortality compared with other female transplant recipients. However, survival among these patients has improved in the last decade, particularly for Black transplant recipients.

Conversion of the HVAD Left Ventricular Assist Device to the Centrimag Using a Customized Apical Plug.

Left ventricular assist device thrombosis is a potentially life-threatening complication often managed acutely with device exchange. In the absence of modifiable risk factors recurrent thrombosis can occur. Recent changes in the heart allocation policy have reduced left ventricular assist device complications from top priority to status 3. In this report we present a patient with recurrent left ventricular assist device thrombosis. Given no modifiable risk factors and recurrence of thrombosis, the HeartWare HVAD ((Medtronic, Minneapolis, MN)) was converted to a temporary Centrimag device device (Abbott, Abbott Park, IL) using a novel plug through the existing sewing ring. With status 2 listing the patient was successfully transplanted on postoperative day 3.

Inferior Vena Cava Reconstruction with Tubularized Bovine Pericardium.

A 32-year-old male presented with a large locally advanced sarcomatoid right renal cell carcinoma invading the duodenum and IVC. Due to persistent symptomatic gastrointestinal bleeding requiring repeat blood transfusion and the inability to utilize appropriate systemic chemotherapy, the patient was taken for palliative resection. En bloc pancreaticoduodenectomy, right nephrectomy and IVC resection were performed with reconstruction of the IVC with tubularized bovine pericardium. Widespread availability, ease and speed of tubularized graft creation, lack of morbidity to the patient and its inherent resistance to infection in contaminated fields make bovine pericardium an expedient reconstructive option in these challenging cases.

Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.

OBJECTIVE: Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. METHODS: Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. RESULTS: Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. CONCLUSIONS: After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation.