Search

Purpose After successful lung transplantation, patients can potentially reach same strength and endurance as healthy individuals. Although high-altitude trekking has been reported after LuTX, data on the patient's physiological adaptation during prolonged exercise in a reduced oxygen environment remains scarce. Methods In September 2019, 14 lung transplanted patients and their accompanying doctors, climbed Mount Jebel Toubkal (4167 m; 13 671 ft), the highest peak in North Africa, High Atlas, Morocco. Participants had regular cardiopulmonary exams (lung function, polysomnography, echocardiography) as well as blood sampling (capillary blood gasses, lactate, creatinine) throughout the expedition up to 3145 m (10 318 ft). Results Patients (♀: n=3 | ♂: n=11) had a median age of 42.1 years (24.8-65.2). Their underlying diagnoses were CF (n=10), Emphysema (n=2), IPF (n=1) and PH (n=1). Median time from LuTX to this expedition was 4.1 Years (1.7-17.6). Controls (♂: n=4) were 31.3 (29.3-46.7) years old. Over 7 days, participants hiked a distance of 81km (50.3 mi) with a cumulative elevation gain of 5496 m (18,031 ft.) vertical distance. Eleven Patients (78.6%) reached the summit whereas three patients had to abort because of altitude sickness (n=1 on day 1 at 2431m) or physical exhaustion (n=2 on day 3 at 3124m and day 6 at 3800m). Blood gas analysis and vital signs did not differ significantly between the patients and four healthy controls (pO2: 59.1 ±8.9 vs. 61.8 ±14.4 mmHg | pCO2: 29.8 ±1.5 vs. 29.8 ±0.5 mmHg | lactate 0.82 vs 0.83 mmol/l). Creatinine was significantly higher in transplanted patients (1.87 vs. 0.97 mg/dl; p=0.025). Conclusion Although technically challenging, medical monitoring of lung transplanted patients is feasible during high altitude hiking. In carefully selected athletic LuTX patients, gas exchange and metabolism didn't differ compared to healthy adults.

Purpose Ex vivo lung perfusion (EVLP) offers a unique potential in evaluation, optimization and transplantation of lungs that would otherwise potentially be rejected. Between 2016 and 2020 208 lung transplants (LuTx) were performed and 22 donor lungs were evaluated by EVLP of which 16 were transplanted. Aim of the study was to compare mid-term results in LuTx recipients with or without the use of EVLP. Methods In a retrospective single-center analysis data from a prospectively collected database were analysed. The EVLP group (n=16) consisted of donor lungs classified as marginal and were evaluated by EVLP and afterwards transplanted. The non EVLP group (n=16) consisted of conventional LuTx recipients matched for age and pulmonary disease. Both groups were compared for the endpoints survival, primary graft dysfunction, rejection episodes and chronic allograft dysfunction. Results Recipient age was 55 ± 6 years in EVLP group and 57 ± 5 years non EVLP group (n.s.). Female gender was present in 36% EVLP patients and 50% non EVLP (n.s.). The rate PGD grade 1 at 72 h post-LTx was 14% in both groups (each2/16). In non EVLP group 1recipient was PGD 2 (7%). PGD3 was present only in the EVLP group 14% (2/16) vs. 0% in control. At last visit, post-LuTx, forced expiratory volume in 1 s (FEV1%) as percentage of predicted best was similar in the EVLP and non-EVLP group (77% vs. 78%). Chronic lung allograft dysfunction was diagnosed in one non EVLP patient and one EVLP patient during follow up post-LuTx. In the EVLP group 2 patients had rejection episodes subjected to treatment and 6 patients in the non EVLP group (n.s.). Survival at 1 year was 81% for the EVLP group and 94% in non EVLP group (n.s.). Conclusion Recipients transplanted with extended criteria donor lungs, thoroughly evaluated by EVLP show similar mid term outcomes as conventionally transplanted lungs from standard donors. EVLP shall increase the number of acceptable donor lungs. Future clinical trials will bring further evidence; clear guidelines regarding application of machine perfusion have to be developed.

Purpose Heart Transplantation (HTX) is an established therapy for endstage Heart Failure with excellent long term results. However, shortage of donor organs leads to increased use of extended criteria organs and rising numbers of high risk recipients on the high-urgency list and on mechanical circulatory support (MCS). Donor organ machine perfusion (MP) allows continuous warm perfusion of the beating heart, thus reducing time of ischemia as well as allowing for standardized evaluation. AIM: analyze outcome of HTX using donor heart MP. Methods In a retrospective single-center study, data from a prospectively collected database were analyzed. From July 2018 to September 2020, eleven hearts were retrieved and perfused using the Organ Care System (OCS), 9 hearts were transplanted. Criteria to use the OCS were 1) estimated ischemic time > 4 hours for any reason, 2) inotropes > 0.25 µg/kg/min, 3) LV-EF Results All patients survived the procedure and the 30-day interval [time since HTX 8-799 d]. No MP related complications were noted. One patient died after 233 days due to sepsis. 4 patients were on temporary ECLS support in the early postoperative period (6-12d) due to initial right ventricular dysfunction. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsies showed no rejection or mild rejection 1R in two cases (21d and 3 months surveillance biopsy). Two donor hearts were rejected after OCS perfusion 1) because of previously unknown coronary artery disease (angiography on OCS) and 2) due to underestimated aortic valve insufficiency and severe septum hypertrophy. Conclusion Ex vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options may increase the number of acceptable donor hearts and improve results. Future clinical trials will bring further evidence, clear guidelines regarding application of MP have to be developed.

Purpose Ex Vivo Lung Perfusion (EVLP) is a promising tool for evaluation and reconditioning in marginal donor lungs. However, the optimal protocol is discussed controversially. It is our hypothesis that different EVLP protocols and different perfusion solutions result in different cytokine patterns during EVLP. Methods Following cardiac arrest and 30 min of no-touch warm ischemia, pig lungs were harvested, flushed and stored in cold preservation solutions. Different groups were processed as immediate long EVLP (I-EVLP, 12 h), delayed short EVLP (4 h) after 9 hours of cold storage (D-EVLP). Lungs were perfused with different acellular solutions: Steen solution or modified HTK solution containing either dextran(CD) or dextran and albumin (CDA). Pulmonary gas exchange, biochemical and structural parameters were recorded hourly. Cytokine / chemokine levels were analyzed in perfusates at baseline and after 1 and 4 h of EVLP. Results ∆ pO2 (pulmonary venous - pulmonary arterialpO2) was higher in D-EVLP group, especially at h 1: I-EVLP: 259 ± 132, D-EVLP: 291 ± 96 and h 2: I-EVLP: 228 ± 125, D-EVLP: 252 ± 116 (n.s.). Compared to D-EVLP, lungs that underwent EVLP with CD and CDA showed significantly higher oxygen capacity (∆ pO2 CD: 402.79 +30.33 mmHg, CDA: 414.86 + 9.77 mmHg). Within 4 h ELVP, concentrations of IFN-γ, TNF-a, IL-1α/β, IL-10, CXCL8 (IL-8) and IL-18 increased significantly (all p Conclusion In a non-heart beating porcine lung donor model with relevant ischemic tissue damage, lungs were perfused with normothermic EVLP. Even after 9 hours cold static preservation (CSP) and 4 hours EVLP lung, function is comparable to direct EVLP. The modified HTK solution with dextran and dextran/ albumin had significantly better oxygenation. Cytokines and chemokines including the cell death marker IL-18 increase during 4 h of EVLP but a delay before EVLP may not dramatically worsen the inflammatory response.

Purpose Although lung transplantation and lung volume reduction (both surgically and endoscopically: LVRS/ELVR) are well established therapies for end-stage emphysema patients, data on LVR prior to LuTX remains scarce. Thus, we aim to analyze the impact of pre-transplant LVR on post-LuTX outcomes. Methods From 1/2015 to 5/2018, 55 patients underwent bilateral LuTX for COPD and α1-AT deficiency at our center. Of those, 7 patients (12.7%) had surgical LVR prior to LuTX and 14 (25.5%) had endoscopic LVR. Those patients were compared to the other 34 patients without previous intervention. Data is presented as LVRS (n=7) vs. ELVR (n=14) vs. controls (n=34). Results Despite a significantly different distribution in sex (female: 21.4% vs. 57.1% vs. 64.7%; p=0.023), no other differences were observed in all other recipient characteristics (age: 58 vs 56 vs. 56 years | BMI: 23.2 vs. 20.9 vs. 22.15 | TLCr: 9.6 vs. 7.9 vs. 7.8L | PAP: 33 vs. 30 vs. 30mmHg | waiting time: 271 (15-2350) vs. 747 (48-2161) vs. 1098 (6-3962) days). The lung allocation score (LAS) at time of LuTX did not show any clinically relevant differences between the three groups (32.5 vs. 32.2 vs. 32.9; p=0.028). 4 patients underwent bilateral LVRS, 3 unilateral LVRS. ELVR was performed with valves in 9 cases and with coils in 6 cases, evenly distributed in all lobes. Median duration from LVR to listing for LuTX was 303 (LVRS) and 508 (ELVR) days. Median duration from LVR to LuTX was 961 (397-3194) and 823 (8-2704) days respectively. After LuTX no significant differences were observed in ICU stay (7 vs. 10 vs. 11 days), hospitalization (48 vs. 41 vs. 51 days) and lung function (3-months post-LuTX FEV1: 80% vs. 78% vs. 79% | 3-months RV: 118% vs. 120% vs. 125%). No significant differences were observed in survival (1 and 3year survival: 100% vs. 100% vs. 85.3; p=0.07). Conclusion In our recent cohort of patients, LVRS and ELVR prior to lung transplantation did not impact short- and medium-term post-LuTX outcomes. Although the benefit and the precise indications of the different LVR methods remain to be elucidated in prospective trials, LVRS and ELVR can be safely considered for patients prior to lung transplantation.

Background To improve the rate of successful heart transplantations, organ preservation should be optimized in cardiac transplantation surgery. Iron-dependent oxidative damage and iron-independent, chloride-dependent injury of the endothelium have been described after cold ischemic storage and reperfusion, leading to an enhanced rate of complications and unfavorable outcomes. This screening study tested the effects of iron chelator supplementation in different histidine–tryptophan–ketoglutarate (HTK) organ preservation solutions on endothelial function in a long-term storage model of the isolated rat aorta. Methods Isolated rat aortic rings underwent a 24-hour cold ischemic preservation in different HTK solutions supplemented with iron chelators of low (deferoxamine) and high (LK-614) membrane permeability. In vascular reactivity measurements we investigated the phenyleprine-induced contraction and both endothelium-dependent and -independent vasorelaxation by using cumulative concentrations of acetylcholine and sodium nitroprusside with and without an additional external oxidant injury during re-oxygenation. Results Traditional HTK solution, Custodiol, failed to prevent endothelial dysfunction in our experiments. Use of chloride-poor HTK solutions containing N-α-acetyl- l -histidine with and without supplementation with LK-614, but not with deferoxamine, resulted in significant improvement of impaired endothelial function; moreover, complete protection of the endothelium was feasible after 24-hour cold storage. Endothelium-independent functions of vascular smooth muscle were not affected in any of the groups. Conclusions Our results demonstrate the important pathophysiologic role of iron-dependent oxidative injury in the development of endothelial dysfunction after cold storage, which can be prevented by cell-permeable iron chelators.

Background The effect of pre- or post-operatively acquired diabetes mellitus on survival after heart transplantation remains controversial. The influence of transplant era on diabetes-associated survival is unknown. Methods A retrospective database analysis was performed on all cardiac transplant recipients followed up at our institution between 1986 and 2003. Diabetes mellitus was diagnosed based on oral glucose tolerance testing. Results Survival was analyzed in 243 patients (80% male, mean age 52.2 years, mean follow-up 5.22 years). Kaplan–Meier survival analysis demonstrated significantly worse ( p = 0.0001) survival both early (months 0 to 12) and late (>5 years) after transplantation in pre-operative diabetics ( n = 53) compared with non-diabetics ( n = 190). Pre-operative diabetes was identified as the only independent risk factor for decreased long-term (>1 year) survival ( p = 0.004). In contrast, no effect on survival ( p = 0.5) was demonstrated in patients becoming diabetic only after heart transplantation ( n = 39). At 12 months post-transplant renal function was significantly impaired in diabetics ( p = 0.025); acute rejection, cytomegalovirus (CMV) infection and transplant vasculopathy occurred with similar frequency. Causes of death were similar in diabetics and non-diabetics. Reduced long-term survival in pre-operative diabetics was seen in the early transplant era (1986 to 1994) ( p p = 0.5). Conclusions Pre-transplant but not post-transplant diabetes confers an adverse risk for survival (short and long term). Diabetes-associated long-term survival appears to have improved in the recent era, supporting continued transplantation in diabetics under close surveillance and aggressive medical management.

Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible.Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+)50/microl (reference500/microl) and T-suppressor cells (CD8+)50/microl (reference300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined.Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%).T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.

Background: The significance of International Society of Heart and Lung Transplantation (ISHLT) grade ≥3A rejection detected by routine endomyocardial biopsies beyond 2 years post-transplant remains uncertain. Methods: We performed a retrospective analysis of our single-institution database consisting of 4,041 biopsies (188 patients) from 1986 to 2001. Incidence, clinical correlates and outcome of ISHLT grade ≥3A rejection beyond 2 years post-transplant were analyzed. Results: A total of 307 ISHLT grade ≥3A rejection episodes was diagnosed up to 10 years after transplantation, 69 of which occurred later than 2 years post-transplant in 33 of 139 patients (“late rejection”) at therapeutic levels of immunosuppression. Late rejection was only marginally correlated with the incidence of moderate rejection within the first 2 post-transplant years ( p = 0.09). The incidence of moderate rejection per patient-year decreased from 1.05 in Year 1 over 0.11 in Year 5 to 0.04 in Year 10. The technical failure rate of biopsies remained low throughout the post-transplant period (range 0.7% to 2.4%). Spontaneous resolution of ISHLT grade ≥3A rejection beyond 2 years post-transplant occurred in all 17 patients in whom specific anti-rejection therapy had been electively withheld. Mortality beyond 2 years post-transplant was lower ( p = 0.033) in the “late rejecting” group ( n = 33) than in the control group ( n = 106). Conclusions: Endomyocardial biopsy continues to detect episodes of moderate rejection even very late after heart transplantation, without a close correlation with the rejection frequency in the early post-transplant period. Even without specific treatment, late rejection carries a benign clinical prognosis and may represent a separate biologic entity. Potential long-term effects—for instance, on the pathogenesis of transplant vasculopathy—need further elucidation.