Risk Of Primary Graft Dysfunction Research Articles

Primary Graft Dysfunction and Early Mortality in Heart Transplants from Drug Overdose Donors

Introduction Over the last two decades, there has been a 24-fold rise in solid organ donation due to drug overdose deaths. One-year survival in recipients of a heart transplant from a drug overdose donor (DOD) has been reported to be similar to that of donor deaths from trauma or other medical causes (non-DOD). However, the incidence of primary graft dysfunction (PGD) requiring mechanical circulatory support (MCS) and early post-transplant mortality in these patients has not been established. Hypothesis Heart donation from a DOD results in higher rates of PGD and early post-transplant mortality than donation from a non-DOD. Methods We performed a retrospective analysis of consecutive orthotopic heart transplants (OHT) at a single center from January 2013 to December 2018. Patients with PGD requiring MCS in the form of extracorporeal membrane oxygenation (ECMO) within 48 hours of OHT were analyzed with respect to the cause of death of the donor. Patients on ECMO prior to transplant surgery were excluded. Baseline characteristics were compared using Chi-square test for categorical variables and t-test for continuous variables. Results Of 154 consecutive heart transplants, 5 were excluded due to pre-operative recipient ECMO support. Among the 149 analyzed transplants, 38 (25.5%) received a heart from a DOD. DOD had a lower initial pH (7.15 vs. 7.28, p=0.001), a higher rate of hepatitis C infection (15.8% vs. 1.8%, p=0.001) and were more likely to have received CPR (91.7% vs.32%, p Conclusions In this single-center study, there was a trend towards an increased risk of PGD when the donor had died from a drug overdose, possibly due to ischemic graft injury related to hypoxia. However, survival to hospital discharge was similar between the DOD and non-DOD groups. Given the rapid increase in the number of DODs, further investigation in larger populations is warranted as it may help inform donor selection.

Endothelial Glycocalyx Shedding Predicts Donor Organ Acceptability and Is Associated With Primary Graft Dysfunction in Lung Transplant Recipients.

The endothelial glycocalyx, a sieve-like structure located on the luminal surface of all blood vessels, has been found to be integral to regulation of capillary permeability and mechanotransduction. Given this, we investigated the role of endothelial glycocalyx breakdown products in organ donors and recipients in terms of acceptability for transplant and risk of primary graft dysfunction (PGD). Endothelial glycocalyx breakdown products were measured in the peripheral blood of 135 intended and actual organ donors. Breakdown product levels were tested for association with donor demographic and clinical data, organ acceptability for transplant along with lung recipient outcomes (n = 35). Liquid chromatography mass spectrometry analysis was performed to confirm glycosaminoglycan levels and sulfation patterns on donor samples (n = 15). In transplant recipients (n = 50), levels were measured pretransplant and daily for 4 days posttransplant. Levels were correlated with PGD severity and intubation time. Decreased hyaluronan levels in peripheral blood independently predicted organ acceptability in intended and actual donors (odds ratio, 0.96; [95% confidence interval, 0.93-0.99] P = 0.026). Furthermore, high donor syndecan-1 levels were associated with PGD in recipients (3142 [1575-4829] versus 6229 [4009-8093] pg/mL; P = 0.045). In recipient blood, levels of syndecan-1 were correlated with severe (grades 2-3) PGD at 72 hours posttransplant (5982 [3016-17191] versus 3060 [2005-4824] pg/mL; P = 0.01). Endothelial glycocalyx breakdown occurs in lung transplant donors and recipients and predicts organ acceptability and development of PGD. Glycocalyx breakdown products may be useful biomarkers in transplantation, and interventions to protect the glycocalyx could improve transplant outcomes.

Off-Pump Bilateral Lung Transplantation via Median Sternotomy: A Novel Approach With Potential Benefits

The clamshell incision is the standard approach for bilateral lung transplantation. There is limited experience with bilateral lung transplantation via median sternotomy, and the use of cardiopulmonary bypass seems to be mandatory in all cases while accepting thepotential disadvantages of the extracorporeal circulation. We describe a novel approach for bilateral lung transplantation as an off-pump technique via median sternotomy. This approach has the potential to combine the advantages of median sternotomy with less postoperative pain, better chest wall function, and reduced risk of primary graft dysfunction and bleeding complications.

Treatment with a Statin or Spironolactone is Associated with a Reduced Risk for Primary Graft Dysfunction and Mortality

Purpose Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality after heart transplantation (HT) and is a significant predictor of adverse outcomes . We aimed to investigate the influence of pharmacologic therapies administered to the recipient before HT on PGD. Methods Between 1997-2017 we assessed 279 HT patients. Pharmacological therapies at the time of HT were reviewed, including a statin, spironolactone , amiodarone , beta-blockers (BBs) and ACE-inhibitors (ACEIs). Endpoints included PGD (defined according to the ISHLT consensus statement), in-hospital mortality, 1- and 5-yr survival. Results In the group of patients diagnosed with PGD (102; 36.5%) vs the non-PGD group, fewer had received pre-HT statins (35 vs 75%, p Multivariate analysis consistently demonstrated that pre-HT treatment with a statin or spironolactone was independently associated with a significant 74% and 87% reduced risk for PGD, while pre-HT amiodarone therapy was independently associated with a significant >4-fold increased risk for PGD (Figure). Statin therapy was independently associated with a significant reduction in PGD severity (OR 0.26, 95% CI 0.03-0.74). In-hospital mortality was significantly lower for patients treated with a statin (9 vs 21%, p=0.006) or spironolactone (7 vs 27%, p Conclusion Pre-HT statin or spironolactone therapies are independently associated with a reduced risk for PGD and mortality, whereas amiodarone therapy is associated with an increased risk.

Donor Hormonal Thyroid Therapy is Associated with Increased Risk of Primary Graft Dysfunction after Heart Transplantation

Donor Hormonal Thyroid Therapy is Associated with Increased Risk of Primary Graft Dysfunction after Heart Transplantation

Donor-Recipient Size Matching via Chest X-ray Measurements and Primary Graft Dysfunction Risk in Lung Transplantation

Purpose Donor to recipient (D-R) lung size matching using predicted total lung capacity (pTLC) has been shown to be associated with the risk of primary graft dysfunction (PGD) following lung transplant (LTx) but the effect varies with underlying recipient diagnosis, potentially owing to differences in actual TLC. Chest x-ray (CXR) measurements to estimate true D-R TLC could account for disease-related effects, but their role in D-R size matching is unknown. We hypothesized that CXR measurements would estimate actual TLC values and that mismatches would increase PGD risk. Methods We retrospectively reviewed adult double lung transplant recipients between 2007 and 2016. We measured lung size on pre-transplant donor and recipient CXRs using apex to costophrenic angle (ACPA) distance (Figure 1A), taking the mean of the left and right (donors the largest of the 3 most recent CXRs; recipients the most recent CXR prior to LTx). We defined “oversized” as D-R ratio > 1 and “undersized” ≤ 1. The primary outcome was grade 3 PGD (presence of edema on CXR + PaO2/FiO2 Results 206 patients met inclusion criteria, 32 (16%) of whom developed grade 3 PGD at 48 or 72 hours. Median D-R ACPA ratio was 0.92 (IQR 0.83-1.09) and recipient ACPA was strongly related to recipient actual TLC (Figure 1B, R2 0.7297 [quadratic]). D-R ACPA ratio was larger in those patients who developed PGD vs. non-PGD cases (1.01 [IQR 0.91-1.18] vs. 0.91 [IQR 0.83-1.07] p = 0.01). Oversizing (ACPA ratio > 1) increased grade 3 PGD risk (adjusted OR 2.3 [95% CI 1.0-5.2], p = 0.04). Conclusion Oversizing via CXR was associated with increased PGD risk. CXR measurement appears to serve as an estimate of true TLC. D-R ACPA ratio shows promise as a size matching tool in donor allocation and requires further investigation.

Donor-Recipient Weight Mismatch and Primary Graft Dysfunction Risk Post-Lung Transplantation

Purpose The relevance of donor-to-recipient weight matching is unknown in lung transplantation, but has been associated with increased 30-day mortality in heart transplants. A lung graft from a lower weight donor could be exposed to a higher cardiac output than it is accustomed to, which may result in increased capillary leak and the development of primary graft dysfunction (PGD). We hypothesized that the risk of severe PGD would be higher in recipients who received lungs from a donor with a lower weight than that of the recipient. Methods We conducted a retrospective review of patients undergoing lung transplantation at our center between January 2004 and December 2016. Lobar and combined heart/lung transplant recipients were excluded. The risk factor of interest was donor-to-recipient weight ratio (DRWr), and primary outcome was PGD3 [partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 ratio) ≤ 200mmHg at 48 or 72 hours post-transplant with bilateral infiltrates on imaging]. We used multivariable logistic regression to test the association between DRWr and PGD3, adjusted for DR height ratio, indication diagnosis, recipient sex, transplant type, donor age, donor smoking exposure > 20 pack years and graft total ischemic time. Results 505 patients were eligible for study, of which 485 (96%) underwent double lung transplant. 96 (19%) recipients developed PGD3. DRWr ranged from 0.38 to 3.46 with a median ratio of 1.01 (interquartile range 0.86 - 1.23). DRWr ≤ 1 was associated with an adjusted odds ratio of 2.27 [95% confidence interval 1.34, 3.96, p=0.003] of developing PGD3. There was a dose response noted (see Figure 1). Donor age (p=0.004) and graft ischemic time (p=0.048) remained significant predictors of PGD3 in the model. Conclusion Lung transplantation from a donor weighing less than the recipient is associated with a higher rate of grade 3 PGD. We hypothesize this is related to increased cardiac output relative to pulmonary vascular surface area of the graft.

Achievement of Donor Management Goals and Primary Graft Dysfunction after Heart Transplant

Purpose Achievement of donor management goals (DMG), predefined critical care endpoints utilized to optimize donors prior to transplant, have been associated with increased organ utilization and decreased incidence of graft dysfunction following kidney transplant . Specifically, acceptable donor urine output and serum sodium have been associated with reduced incidence of renal graft dysfunction . This may reflect more optimal underlying donor health or improved critical care management. Association of DMG and outcomes following HT, including primary graft dysfunction (PGD), have not been previously described. Methods A cohort of HT recipients at our institution between 2012 to 2017 (n=645) was linked to their respective donors that were present in the UNOS DMG Registry (n=572). PGD was defined according to ISHLT criteria. DMG Registry variables with less than 15% missing values were subject to univariate logistic regression with PGD as the response variable (143 variables). Statistically significant variables were then subject to multivariable logistic regression. Results Moderate-severe PGD occurred in 46 (8%) HT recipients. Achievement of an increasing number of DMG was not associated with a decreased risk of PGD (p = 0.28). However, meeting the urine output DMG at authorization was associated with a decreased risk of PGD (OR 0.47, p=0.023). This remained significant after controlling for other donor and recipient factors (TABLE). Conclusion Achievement of the urine output DMG was associated with a decreased risk of PGD after HT. A proposed mechanism may be improved renal perfusion reflecting optimal cardiac output. Although achieving DMG appears to represent more healthy donors, further research is needed to understand physiologic mechanisms of decreased donor urine output and PGD.

Risk Factors for Primary Graft Dysfunction in Patients with Cystic Fibrosis Receiving Lung Transplants

Purpose The primary driver of poor outcomes in the early stages of lung transplantation is primary graft dysfunction (PGD). Patients with cystic fibrosis (CF) have unique physiology and demographics compared to other lung transplant recipients. Therefore, we sought to identify risk factors for PGD in the CF patient population undergoing lung transplantation. Methods We utilized clinical data on lung transplant recipients with CF and their donors from the Lung Transplant Outcomes Group cohort, a multi-center prospective cohort study of PGD pathogenesis. The primary outcome was grade 3 PGD within the first 72 hours after transplantation. Potential covariates were identified in univariate analysis and assessed for collinearity. Independent PGD risk factors were identified using multivariate logistic regression. A sensitivity analysis was performed using grade 3 PGD 48 to 72 hours after transplantation. Results We identified 195 patients with CF who received lung transplants between August 2014 and June 2018 across ten centers. Grade 3 PGD developed in 80 subjects (41%). Risk factors for PGD in CF patients based on the multivariable model were white donor race (odds ratio [OR]: 2.6, 95% confidence interval [CI]: 1.4-5.1), any positive panel reactive antibodies (PRA) (OR: 2.2, 95% CI: 1.0-4.7), recipient female gender (OR: 2.1, 95% CI: 1.1-3.9), intraoperative cardiopulmonary bypass use (OR: 2.2, 95% CI: 1.2-4.2), increasing lung allocation score (LAS) (OR: 1.2 per 10 point increase in LAS, 95% CI: 1.0-1.4), and ECMO (extracorporeal membrane oxygenation) bridge to transplant (OR: 2.7, 95% CI: 1.1-6.7). LAS and ECMO were assessed in separate models due to their collinearity. Mean pulmonary artery pressure at the time of transplant was included as a potential confounder. Similar findings were seen in a more severe phenotype of PGD that developed 48 to 72 hours after transplant. Conclusion The CF population is often considered to be at low risk of PGD, however we observed a relatively high rate of PGD in this study. Any positive PRA, female recipient gender, intraoperative bypass, increasing LAS, and ECMO are PGD risk factors that have been identified non-CF transplant populations. We validated these risk factors in recipients with CF. White donor race is a novel risk factor that has not been previously identified in lung transplant recipients with another primary diagnosis.

Elevated pre-transplant left ventricular end-diastolic pressure increases primary graft dysfunction risk in double lung transplant recipients.

Primary graft dysfunction (PGD) represents ischemia‒reperfusion injury in the lung allograft, and elevated left ventricular end-diastolic pressure (LVEDP) may contribute to capillary leak. We tested whether pre-transplant LVEDP or pulmonary capillary wedge pressure (mPCWP) are related to PGD risk. We hypothesized that elevated LVEDP and mPCWP would increase PGD risk. We reviewed adult double lung transplant recipients at the University of Alberta Hospital from 2004 to 2016 with pre-transplant LVEDP measurements. The primary outcome was Grade 3 PGD at 48 to 72 hours post-transplant. We used regression analysis to assess the association between LVEDP and mPCWP with Grade 3 PGD risk, as well as agreement between these measurements. Three hundred thirty double lung transplant recipients were included in the study, and 63 (19%) developed Grade 3 PGD at 48 or 72 hours. Mean LVEDP was 16 ± 7 mm Hg in the Grade 3 PGD group and 12 ± 5 mm Hg in the non-PGD group (p < 0.0001). LVEDP >15 mm Hg was associated with an adjusted odds ratio (OR) of 3.83 (95% confidence interval [CI] 1.90 to 7.73, p < 0.0001), whereas mPCWP >15 mm Hg showed similar findings (adjusted OR 4.25 [1.83 to 9.86], p = 0.0008). Correlation and agreement between LVEDP and mPCWP were fair. Elevated pre-transplant LVEDP increases the risk of severe PGD after lung transplant, as does elevated mPCWP. These measurements appear to be complementary as markers of prospective PGD risk.

Evaluation of trazodone and quetiapine in patients with Alzheimer's type dementia and sleep disturbance

Primary graft dysfunction (PGD) represents ischemia‒reperfusion injury in the lung allograft, and elevated left ventricular end-diastolic pressure (LVEDP) may contribute to capillary leak. We tested whether pre-transplant LVEDP or pulmonary capillary wedge pressure (mPCWP) are related to PGD risk. We hypothesized that elevated LVEDP and mPCWP would increase PGD risk.We reviewed adult double lung transplant recipients at the University of Alberta Hospital from 2004 to 2016 with pre-transplant LVEDP measurements. The primary outcome was Grade 3 PGD at 48 to 72 hours post-transplant. We used regression analysis to assess the association between LVEDP and mPCWP with Grade 3 PGD risk, as well as agreement between these measurements.Three hundred thirty double lung transplant recipients were included in the study, and 63 (19%) developed Grade 3 PGD at 48 or 72 hours. Mean LVEDP was 16 ± 7 mm Hg in the Grade 3 PGD group and 12 ± 5 mm Hg in the non-PGD group (p < 0.0001). LVEDP >15 mm Hg was associated with an adjusted odds ratio (OR) of 3.83 (95% confidence interval [CI] 1.90 to 7.73, p < 0.0001), whereas mPCWP >15 mm Hg showed similar findings (adjusted OR 4.25 [1.83 to 9.86], p = 0.0008). Correlation and agreement between LVEDP and mPCWP were fair.Elevated pre-transplant LVEDP increases the risk of severe PGD after lung transplant, as does elevated mPCWP. These measurements appear to be complementary as markers of prospective PGD risk.

RNA Sequencing Reveals the Suitability of Cardiac Death Livers for Transplantation.

Background Organ transplantation is considered the best treatment for end-stage organ failure. However, the lack of available organs for transplantation and the increasing number of patients waiting for transplants are primary issues facing the transplant community. Thus, developing strategies to increase the number of donors, especially for liver transplantation, has become a priority. The use of organs acquired from donors who suffered cardiac related deaths has increased the pool of potential liver donors. However, donation after cardiac death (DCD) livers increases the risk of primary graft dysfunction. Methods In the current study, we conducted transcriptome sequencing using livers from a DCD rat to assess the short-term feasibility and functional efficacy of DCD livers. RNA sequencing (RNAseq) data showed that the liver transcriptome varied greatly in rat livers subjected to 15 minutes of cardiac arrest. Results The livers used in the current study had a significant loss of normal function before transplantation. Functional and network analyses consistently indicated that transcription and translation processes were inhibited after approximately 15 minutes of cardiac arrest. Moreover, the transcriptomic sequencing data provides significant insight for identifying functional genes and testing additional biological questions in DCD liver transplantation in future studies.

Donor-recipient ethnic mismatching impacts short- and long-term results of heart transplantation.

The impact of donor-recipient ethnic matching on heart transplantation (HT) has been poorly studied with inconclusive results. We aimed to investigate the impact of ethnic matching on HT outcomes in Israeli multiethnic patients. The study comprised 168 patients who underwent HT from 1990-2017. Patients and their donors were ethnically categorized to Jews and Arabs. Primary end points were all-cause in-hospital and late mortality; secondary end points included primary graft dysfunction (PGD), rejections, and vasculopathy. Donor-recipient ethnic matching was found in 111 patients, while 57 were ethnically mismatched. Baseline characteristics were similar in both groups. Ethnic mismatching was associated with >7-fold (P=0.018) increased risk for in-hospital mortality and >8-fold (P<0.001) increased risk for PGD. Kaplan-Meier survival analysis showed that overall survival at 10years was significantly higher among matched patients (73% vs 43%, log-rank P<0.001). Multivariate analysis showed that ethnic mismatching was associated with an approximately fourfold higher risk for death (P<0.01). These findings were validated by propensity score analysis. The ethnic mismatched group experienced significantly higher rejection rates compared with the matched group with lower survival free of rejections (log-rank P=0.029). No differences in vasculopathy were found. Donor-recipient ethnic mismatch is an important independent predictor of early- and long-term outcomes following HT, and is associated with increased risk for PGD, rejections, and mortality. These findings will help to design tailored treatment protocols leading to improved outcomes after HT.

Donor Club Cell Secretory Protein G38A Polymorphism Is Associated With a Decreased Risk of Primary Graft Dysfunction in the French Cohort in Lung Transplantation.

Club Cell Secretory Protein (CCSP) G38A polymorphism has recently been involved in lung epithelial susceptibility to external injuries. Lung transplantation (LT) is currently limited by ischemia-reperfusion injury leading to primary graft dysfunction (PGD). We thus hypothesized that donor CCSP G38A polymorphism might impact the risk of PGD after LT. We focused on LT included in the French multicentric Cohort in Lung Transplantation (COLT), performed between January 2009 and December 2014, and associated with preoperative blood samples from the donor and the recipient. Characteristics of the donors, recipients, procedures, early and late outcomes were prospectively recorded in COLT. The CCSP serum concentration and CCSP gene G38A polymorphism were retrospectively determined in a blind manner. Their association with grade 3 PGD was studied in univariate and multivariate analysis. The study group included 104 LT donors and recipients, 84 with grade 0 to 2 PGD and 20 with grade 3 PGD. Preoperative CCSP serum concentration was significantly higher in the donors (median, 22.54 ng/mL; interquartile range, 9.6-43.9) than in the recipients (median, 7.03 ng/mL; interquartile range, 0.89-19.2; P < 0.001) but none impacted the risk of grade 3 PGD (P = 0.93 and P = 0.69, respectively). Donor CCSP G38A polymorphism was associated with a decreased risk of grade 3 PGD in univariate (AG + AA 3/21 = 14.2% vs GG 10/26 = 38.4%, P = 0.044) and multivariate analysis (odds ratio associated with AG + AA, 0.22; 95% confidence interval, 0.041-0.88; P = 0.045), but recipient CCSP G38A polymorphism was not. Donor CCSP G38A polymorphism is associated with a decreased risk of severe PGD after LT in the COLT study. These findings should be confirmed in the frame of a prospective study.

Right Heart Failure during Support with a Left Ventricular Assist Device is Associated with Primary Graft Dysfunction after Heart Transplantation

Introduction Primary graft dysfunction (PGD) is a devastating complication of heart transplantation that is associated with high rates of morbidity and mortality. Right heart failure (RHF) while on LVAD support may identify patients at higher risk for post-transplant complications. This study investigated the relationship between RHF while on LVAD support and post-transplant outcomes. Methods Patients with durable, continuous-flow LVADs who were transplantated between 2010 and 2016 at Barnes-Jewish Hospital were included. Data collection was performed through retrospective chart review. RHF was defined as the need for right ventricular assist device, the extended use of inotropes for more than 14 consecutive days post-LVAD implant, the need to reinitiate inotropes after 14 days but before 30 days after LVAD, or heart failure requiring medical intervention >30 days after discharge from LVAD implantation. The primary outcome was the incidence of PGD after transplant compared between patients with and without RHF. Secondary outcomes included 30-day and 1-year survival, incidence of vasoplegia, severity of PGD, and outcomes stratified by type of RHF. A multivariate logistic regression model was created and included baseline characteristics differing between groups using a p-value of Results Among the 141 patients included in the study, 41 developed RHF while supported with an LVAD. The cohort had a median age of 58, was mostly male (78.7%), and mostly white (74.5%). Most patients had a non-ischemic cardiomyopathy (57%) and were implanted with a HeartMate II LVAD (84.4%). The RHF group had a higher incidence of donor-recipient weight mismatch (3.0% vs. 14.6%, p=0.018) and lower donor EF (55% vs 60%, p=0.018), with no other significant differences in baseline characteristics. In the RHF cohort, 18 patients developed PGD as compared to 14 patients in the group without RHF (43.9% vs. 14.0%, p Conclusions The results of this study show that patients supported with LVADs who develop early severe or late RHF are at increased risk of PGD and death following cardiac transplantation. Donor factors may further increase the risk of these outcomes and should be carefully assessed in this high-risk group. Given the striking increase in PGD, increased vigilance for PGD and aggressive early hemodynamic support should be anticipated for these patients.

Risk of severe primary graft dysfunction in patients bridged to heart transplantation with continuous-flow left ventricular assist devices.

Primary graft dysfunction (PGD) remains a significant cause of post-transplant morbidity and mortality. The exact mechanism and risk factors for this phenomenon remain unknown in the contemporary era. In this study we reviewed adult patients undergoing heart transplantation (HT) at our institution between 2009 and 2017. Severe PGD was defined as the need for mechanical circulatory support (MCS) within the first 24 hours after HT. Multivariate logistic regression analysis was used to identify risk factors for severe PGD, focusing on those bridged to transplant (BTT) with a continuous-flow left ventricular assist device (CF-LVAD). Fifty-six of 480 (11.7%) HT patients experienced severe PGD. Eighty percent of the severe PGD patients were BTT with a CF-LVAD (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.94 to 7.68, p < 0.001). Among the BTT patients, significant associations between >1 year of CF-LVAD support (OR 2.48, 95% CI 1.14 to 5.40, p = 0.022), pre-HT creatinine (OR 3.35, 95% CI 1.42 to 7.92, p = 0.006), elevated central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio (OR 3.32, 95% CI 1.04 to 10.60, p = 0.043), use of amiodarone before HT (OR 2.69, 95% CI 1.20 to 6.20, p = 0.022), and severe PGD were identified. RADIAL score did not accurately predict severe PGD in this contemporary cohort. Those patients who developed severe PGD had decreased 1-year post-transplant survival (78.3% vs 91.8%, p = 0.007). Use of CF-LVAD as BTT is associated with an increased risk of severe PGD. Increased time on device support, renal dysfunction, right ventricular dysfunction as assessed by CVP/PCWP ratio, and pre-transplant amiodarone may identify those patients at high risk. Further research is warranted focusing on optimal timing of device implantation and transplantation, as well as the underlying mechanisms of PGD.

Inhibition of Neutrophil Serine Proteases by Alpha 1 Antitrypsin in Perfadex Preserves Primary Graft Functions of Transplanted Murine Donor Lungs

The risk of primary graft dysfunction (PGD) of donor lungs and early postoperative mortality after lung transplantation (LTx) increases with prolonged preservation times. PGD is triggered by early infiltrating neutrophils which release large amounts of elastase-related serine proteases and inflict irreversible damage on lung graft after cold ischemic storage. Cold ischemic storage for only 6 hours is generally accepted, when lungs are cooled down and preserved in Perfadex immediately after their removal from donors. The need of short preservation times reduces donor lung usage and narrows the geographical area of organ retrieval and transportation. We aimed to increase preservation times beyond 6 hours without impairing the early post-LTx outcome by adding alpha 1 antitrypsin (AAT), a serine-proteases inhibitor of human plasma, to the ice-cold storage solution. We hypothesized that AAT added to Perfadex would protect transplanted lungs against PGD and early graft failure by neutralizing serine proteases from activated neutrophils.

Elevated Pre-transplant Left Ventricular End Diastolic Pressure is Associated With Increased Risk of Primary Graft Dysfunction in Lung Transplant Recipients

Elevated Pre-transplant Left Ventricular End Diastolic Pressure is Associated With Increased Risk of Primary Graft Dysfunction in Lung Transplant Recipients

Lobar Lung Transplantation from Brain-dead Donors in Pulmonary Hypertension

Lobar lung transplantation is known as an alternative for higher Donor/Receiver mismatch in cystic fibrosis or idiopathic pulmonary fibrosis patients. Using lobar lung transplantation for Pulmonary Hypertension remains questionable because of the higher risk of primary graft dysfunction. We thought to determine wether lobar lung transplantation from brain-dead donors is an option for Pulmonary Hypertension.

Higher FiO 2 and Elevated Cell-Free Hemoglobin Augment the Risk of Primary Graft Dysfunction Through Direct Effects on Lung Vascular Permeability

Elevated recipient circulating cell-free hemoglobin (CFH) prior to lung transplant is an independent risk factor for primary graft dysfunction (PGD) (JHLT 2013;32:S42-3). This association is augmented by higher reperfusion FiO2, but the mechanisms of this are unknown. We hypothesized that hyperoxia increases PGD risk through oxidation of CFH, resulting in lung endothelial injury and vascular permeability.