Surgical Myocardial Revascularization with a Composite T-graft from the Left Internal Mammary Artery-Comparison of the Great Saphenous Vein with the Radial Artery.

BACKGROUND: Composite T-grafts between left internal mammary artery (LIMA) and radial artery (RA) are a common concept in complete arterial myocardial revascularization. The aim of the present study was to investigate whether the use of the great saphenous vein (SV) instead of RA leads to comparably good results in terms of outcome in this context. METHODS: Patients who underwent myocardial revascularization with a T-graft using RA or a segment of SV to the right coronary artery or circumflex artery between the beginning of 2014 and the end of 2019 at the Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel were included. To minimize surgical variation, only patients were observed by a single senior surgeon in the department. Exclusion criteria were previous cardiac surgery, preoperative extracorporeal circulatory support, off-pump surgery, additional aortocoronary bypasses, and cardiac combination procedures. RESULTS: A total of 115 patients were studied. In 55 patients, the T-graft was placed between the LIMA and SV, and in 60 patients, the T-graft was placed between the LIMA and RA. Patients in the SV group were older (70.6 ± 7.8 vs. 58.5 ± 10.0 years; p < 0.001), suffered more frequently from non-ST elevation myocardial infarction (12.7 vs. 1.7%; p = 0.027), arterial hypertension (83.6 vs. 61.7%; p = 0.009), and atrial fibrillation (18.2 vs. 1.7%; p = 0.003). They were less likely to be active smokers (16.4 vs. 38.3%; p = 0.009) and less likely to have a history of variceal surgery (0 vs. 15.0%; p = 0.003). Calcification of the ascending aorta was also found more frequently in the saphenous group (18.2 vs. 3.3%, p = 0.009). Operative times and number of distal anastomoses did not differ significantly between the two groups. Postoperative deliriums (16.7 vs. 5.0%; p = 0.043) were observed more frequently in venous patients. Wound healing disorders of the leg (11.1 vs. 0%; p = 0.011) did only occur in SV group and wound infections of the arm only in the RA group. Complete follow-up was achieved in 74.8% of cases. Median follow-up was 60.3 (39.6; 73.2) months. Serious adverse cardiac-cerebral events (19.0 vs. 22.7%; p = 0.675) and mortality (14.5 vs. 6.7%; p = 0.167) did not differ significantly between the groups at follow-up. Myocardial infarction (0 vs. 2.5%; p = 1.000) and stroke (0 vs. 7.5%; p = 0.245) were observed exclusively in RA group. Percutaneous coronary intervention was required in single patients of RA group (0 vs. 15.0%; p = 0.028). No patient from either group underwent repeat coronary artery bypass grafting (CABG). The patients of SV group had angiographically competent grafts and open anastomoses. Graft failure was noted in a single patient in RA group, in which case both grafts and native coronary vessels were stented. Kaplan-Meier analysis revealed no significant survival disadvantage for SV group compared with RA group. CONCLUSION: CABG with a composite T-graft between LIMA and a segment of SV may be comparable to bypass surgery with a composite T-graft between LIMA and RA. This might be true in terms of morbidity and mortality over an intermediate-term observation period. The results of our studies give rise to the hypothesis that the decision not to perform aortic bypass anastomosis may be more important than the choice of graft material.

Dangerous surgical scavenger hunt: the complicated course of a patient with left ventricular assist device and end-stage renal disease undergoing reconstructive flap surgery.

Patients with left ventricular assist devices (LVADs) who develop stage IV sacral pressure sores (SPS) have an increased procedural risk. We present the complications, including severe intra- and postoperative bleeding, diarrhea with metabolic acidosis, volume loss and acute on chronic renal failure, flap dehiscence and late LVAD outflow cannula thrombosis, in a 54-year-old male who underwent diverting ileostomy (DI) and subsequent fasciocutaneous flap (FCF) surgery for stage IV SPS while supported with an LVAD. Our experience suggests that, despite continuous heparinization, life-threatening thrombotic complications, such as device clotting, can occur. Therefore, the benefit of intervention has to outweigh the risk of bleeding, which should be managed with meticulous surgical technique and substitution of red blood cells rather than the reversal of heparinization or the substitution of clotting factors. Continuation of double anti-platelet therapy should also be considered.

Thromboelastometric detection of clotting Factor XIII deficiency in cardiac surgery patients.

AIM(S): In this article, we aimed to investigate plasma Factor XIII levels after extracorporeal circulation in cardiac surgery by thromboelastometric detection, as extracorporeal circulation causes various coagulation disorders due to the exposure of blood to artificial surfaces, inflammatory induction and mechanical destruction of platelets and coagulation factors, which may particularly affect factors with long half-lives, such as Factor XIII. BACKGROUND: Since transfusion algorithms are often empirical and laboratory analysis of Factor XIII plasma levels may not be available 24 h a day, bed-side testing using rotational thromboelastometry (ROTEM) could offer a splendid option to define the cause of excessive peri-operative bleeding disorders in general and Factor XIII levels in particular in a timely manner and thus facilitating exact substitution therapy. METHODS: In this trial, we investigated 25 cardiac surgery patients with extracorporeal bypass times over 100 min. Standard laboratory and ROTEM analyses were performed post-operatively at the time of intensive care unit admission and 6 h later. We implemented EXTEM with additional Factor XIII (teenTEM) as additional test by adding 0·625 IU Factor XIII to standard EXTEM reagents. RESULTS: In this observational study, we could not demonstrate a correlation between Factor XIII and MCFEXTEM , CFTEXTEM or MLEXTEM . Neither Factor XIII plasma levels nor MCFEXTEM could predict blood loss. In accordance with previous findings, we were able to demonstrate increased maximum clot firmness (MCF), decreased clot formation time and decreased maximum lysis by adding Factor XIII in vitro (teenTEM vs EXTEM) indicating an improvement in the coagulation process. As shown before, we also found a strong correlation between MCF and platelet and fibrinogen plasma levels. CONCLUSION: In summary, 'teenTEM' test does not seem to detect Factor XIII deficient patients in cardiac surgery. Furthermore, post-operative blood loss could not be predicted neither by ROTEM nor by laboratory analysis of Factor XIII. In vitro administration of Factor XIII appears to improve laboratory measures of haemostasis.

Unprotected left main coronary artery disease. Surgical therapy.

Coronary artery bypass grafting (CABG) has been established as a safe concept in the treatment of unprotected left main coronary artery (ULMCA) disease and is considered the first-line treatment in current interdisciplinary guidelines. Regardless of the complexity of the lesion and the concomitant diseases, CABG is associated with excellent long-term results. Randomized controlled trials investigating the role of percutaneous coronary intervention in the setting of ULMCA lesions are frequently underpowered and suggest that, when restricted to less complex lesions, percutaneous coronary intervention is associated with results comparable to surgery. Thus, there is an urgent need for further randomized controlled trials RCTs with all-comers design to supply precise data under real-life conditions representative of the left main stem anatomy. Until then, an interdisciplinary approach to patients with ULMCA lesions is mandatory in view of the existing guidelines.

The Relationship Between FoxP3 and SOCs3 Gene Expressions and Disease Activity in Rheumatoid Arthritis.

BACKGROUND: Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity. METHODS: We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR). RESULTS: Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients. CONCLUSION: FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity.

First experience with the new portable extracorporeal membrane oxygenation system Cardiohelp for severe respiratory failure in adults.

BACKGROUND: Over the last decade, technical improvements in extracorporeal membrane oxygenation (ECMO) equipment have reduced procedure-related complications and have made ECMO an effective option for patients with acute respiratory distress syndrome (ARDS) if conventional therapy fails. METHODS: In this report, we present our early experience with the Cardiohelp, a new portable miniaturized ECMO system, in 22 consecutive patients with ARDS. All patients were placed on venovenous ECMO. Cannulas were inserted percutaneously, employing the Seldinger technique. Data were collected prospectively. RESULTS: The median patient age was 47 years (36 to 61). Fifteen patients from regional hospitals were too unstable for conventional transport and were placed on Cardiohelp at the referring hospital and then transported to our institution. The patients were transported by ambulance (n=2) or helicopter (n=13) over a distance of 50-250 km. Cardiohelp support resulted in immediate improvement of gas exchange and highly protective ventilation. The median duration of support was 13 days (8 to 19). An exchange of the device was necessary in 9 patients. Sixteen patients (72.7%) were successfully weaned from ECMO and fifteen patients (68.2%) survived. Device-related complications were not observed. CONCLUSIONS: The compact portable ECMO device Cardiohelp is a highly effective method to secure vital gas exchange and to reduce further ventilator-induced lung injury in patients with acute respiratory failure. Crucial technical innovations and ease of device transport and implantation allow location-independent stabilization with consecutive inter-hospital transfer.

Successful use of a percutaneous miniaturized extracorporeal life support system as a bridge and assistance to left ventricular assist device implantation in a patient with severe refractory cardiogenic shock.

We present a 51-year-old man with cardiogenic shock in whom a percutaneous extracorporeal life support system (ECLS) was inserted to restore cardiopulmonary stability. After successful stabilization, a left ventricular assist device was implanted, using the ECLS without switching to a conventional cardiopulmonary bypass system to reduce its side effects.

Frequency of Genotypes and Allelic Polymorphisms of Vitamin D Receptor in Egyptian Psoriatic Patients and Their Association With Disease Severity, Immune Modulation of IL-22 Levels and The Response to Topical Calcipotriol Treatment: A Case Control Study.

Objective: This study was performed to determine the genotype and allelic frequencies (polymorphisms) of the four genes of vitamin D receptor (VDR) among Egyptian psoriatic patients and healthy controls to explore their association with disease severity (PASI) score and immune modulation of IL-22 cytokine and to predict the response to topical calcipotriol treatment. Patients and Methods: The frequencies of the four VDR gene polymorphisms (FokI, ApaI, TaqI, and BsmI) in blood samples of 51 adult Egyptian patients with psoriasis vulgaris and 50 healthy controls were evaluated using restriction fragment length polymorphism (RFLP)-PCR. Serum levels of IL-22 were measured by ELISA. Results: The most frequent genotype (wild) in the studied patients was Apa1; AA (88.2%) followed by Fok1; FF (47.1%) and Taq1; TT (47%), while Bsm1; BB genotype was (27.7%). The most frequent allele polymorphisms either in one allele (Bb) or both alleles (bb) in psoriatic patients were 72.5%, followed by Ff, ff (52.9%) and Tt, tt (52.9%). The less frequent allelic polymorphism was Aa, aa (27.7%). Insignificant differences in the frequency of genotype (wild) and allelic polymorphisms were detected between patients and controls (P > 0.05). A significantly higher serum concentration of IL-22 (ng/mL) was detected in patients than controls (P = 0.001). Further, 66.6% of patients displayed a clinical response, while 33.4% were non-responders. A significantly higher expression of TaqI polymorphism was detected in (100%) of non-responders (P < 0.001), which was also correlated with disease severity (r = 0.515, P < 0.01). Conclusion: These results suggest that the VDR TaqI polymorphism is the only gene correlated to psoriasis susceptibility in the Egyptian population, and affects the response to topical calcipotriol treatment but does not affect IL-22 immune modulation.

Residual Bone Marrow T & NK-Cells at Diagnosis in Pediatric Pre-B-ALL: A Case-Control Study.

Background: Mature bone marrow T lymphocytes and NK may have a special relevance in the control of the malignant growth. Objective: We aimed to assess the percentage of the residual BM T-cells, (T-helper -T-cytotoxic- NKT) and the NK cells of childhood precursor B-lymphoblastic leukemia (B-ALL) as an indicator of innate and adaptive immunity in these patients. Subjects and Methods: This study was conducted on 40 B-ALL patients, and 40 apparently healthy matched children served as a control group. The flow cytometry was used to assess the percentage of the residual BM T-cells (T-helper, T-cytotoxic and NKT), and the NK cells. Results: Compared with the control group, the percentage of the residual BM T-cells, its subtypes (T-helper, T-cytotoxic), and NKT cells in addition to the NK cells was significantly decreased in Group IA, and Group IB, but there was no significant difference between Group IA and Group IB in all studied parameters. In terms of the CD4/CD8 ratio, there was a significant increase in Group IA as compared to the control group (P < 0.026), but there were no significant statistical differences in CD4/CD8 ratio between Groups IB, and the control. Likewise, in CD4/CD8 ratio between groups IA, and Groups IB (P > 0.05). The percentage of NK, and NKT cells shows a significant increase in Hepatomegaly and Splenomegaly, as compared to non-Hepatomegaly and non-Splenomegaly patients of Groups IB (P < 0.05). However, there was a significant increase in statistical differences in the percentage of NKT cell between non-Splenomegaly, as compared to Splenomegaly patients of Group IA (P < 0.05). Additionally, there is a negative correlation between B.M Blast% to CD4/CD8 ratio and NK%, but there is no significant correlation between B.M Blast% to NK T% in the group 1 A.

Urinary IgG, serum CX3CL1 and miRNA-152-3p: as predictors of nephropathy in Egyptian type 2 diabetic patients.

The purpose of this study was to assess the role of urinary IgG, serum CX3CL1 and miRNA 152-3p levels as predictors of nephropathy in type 2 Egyptian diabetic patients. Sixty type 2 diabetic patients and twenty healthy controls were enrolled in a cross-sectional study. Then they were grouped into: three groups based upon urine albumin excretion (UAE). The expression of miRNA 152-3p in serum was measured using quantitative polymerase chain reaction (RTq-PCR). Serum CX3CL1 and urinary IgG concentrations were measured by ELISA. RTq-PCR revealed that serum miRNA-152-3p levels in patients were significantly higher than in controls. There was significant differences between group with normoalbuminuria and groups with diabetic nephropathy DN as regard to age, duration of nephropathy, Albumin/Creatinine ratio (A/C ratio), creatinine, urine IgG, CX3CL1 and HbA1c. In diabetic patients, there was a significant positive correlation between miRNA-152-3p levels and disease duration only as well as significant positive correlations between urinary IgG levels and age, disease duration, serum creatinine, A/C ratio, and urea. Positive correlation between serum fractalkine CX3CL1 level and age, duration of disease, urea, creatinine, A/C ratio, HbA1C and IgG in patient with DN. Serum CX3CL1 level, urinary IgG were significantly increased with the progress of nephropathy so these integrated biomarkers could be used as good predictors for early identification of nephropathy. But miRNA- 152-3p has inadequate prognostic indicator for ESRD progression.

Impact of the Eurotransplant high-urgency heart allocation system on the outcome of transplant candidates in Germany.

BACKGROUND: In 2000, the Eurotransplant Foundation changed the allocation criteria following the enactment of the German Transplantation Law (GTL). Our study investigated the impact of the new allocation system on outcomes after heart transplantation (HTx) in Germany. METHODS: We compared 2 cohorts of patients who underwent HTx at our institution in two different 3-year periods before (Group 1: 01/1995-12/1997) and after (Group 2: 01/2003-12/2005) implementation of the new system. RESULTS: An increase in the ratio of HTx performed on an urgency basis was found in Group 2 (8.3 % vs. 87.2 %; P < 0.001). The median waiting time and the ischemia time were significantly lower in Group 1 ( P < 0.05). Postoperatively, the length of ICU stay was significantly higher in Group 2 ( P = 0.04). CONCLUSION: The new allocation system decreased the proportion of local and regional organ harvesting. It generates a higher ischemia time without increasing the number of transplantations and without improving the clinical outcome after HTx. The severity of heart failure, rate of secondary organ impairment, and comorbidity is markedly elevated in patients waiting for HTx on HU.

Biologically formed silver nanoparticles and in vitro study of their antimicrobial activities on resistant pathogens.

BACKGROUND AND OBJECTIVES: Silver nanoparticles (AgNPs) have been found to have multiple uses as antibacterial, antifungal and anti-biofilm agents because of their biological activities and safety. The present study was aimed to analyze the antimicrobial and anti-biofilm activities as well as the cytotoxic effect of AgNPs against different human pathogens. MATERIALS AND METHODS: AgNPs were synthesized using cell free supernatants of Escherichia coli (ATCC 25922), Enterococcus faecalis (ATCC 19433), Pseudomonas aeruginosa (ATCC 27856), Enterobacter cloacae (ATCC 13047) and Penicillium oxalicum strain, then were analyzed using UV/Vis Spectral Analysis, Transmission electron microscopy (TEM). Scanning Electron Microscope (SEM) and Energy Dispersive-X-ray Spectroscopy (EDX) analysis. Antimicrobial activities of biosynthesized AgNPs were assessed with selected antimicrobial agents against multidrug resistant bacteria and candida. Anti-biofilm and cytotoxicity assays of these biosynthesized AgNPs were also done. RESULTS: The synthesis of AgNPs were confirmed through observed color change and monitoring UV-Vis spectrum which showed homogeneous (little agglomeration) distribution of silver nanoparticles. TEM and SEM have shown that the particle size ranged from 13 to 34 (nm) with spherical shape and a high signal with EDX analysis. Antibacterial and antifungal efficacy of antibiotics and fluconazole were increased in combination with biosynthesized AgNPs against resistant bacteria and candida. Significant reduction in biofilm formation was found better with Penicillium oxalicum AgNPs against biofilm forming bacteria. CONCLUSION: Penicillium oxalicum has the best effect towards synthesizing AgNPs, for antimicrobial activities against resistant bacteria and candida, in addition to anti-biofilm activities against biofilm forming Staphylococcus aureus and E. coli and the safest cytotoxicity effect on (MRC-5) cell line.

Mild-to-moderate COPD as a risk factor for increased 30-day mortality in cardiac surgery.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is still a serious comorbidity in surgical procedures. We assessed the impact of mild to moderate COPD in a modern cardiac surgery unit. METHODS: An age-, gender- and operation-matched cohort analysis of 242 patients treated between 01/2006 and 12/2008 was performed. COPD was defined as a FEV1 < 80 % and a FEV1/FVC ratio < 0.7 in preoperative spirometry. Primary end point was 30-day mortality. RESULTS: Preoperative beta-agonist treatment of COPD patients was noted for 43 % of patients and not in the control group. After comparable surgery, postoperative respiratory failure was more frequent in COPD patients (10.4 % vs. 2.5 %, P = 0.02), whereas median ventilation time (12 h) and rate of reintubation (2.5 % vs. 3.5 %) did not significantly differ between both groups. Intensive care and hospital stay were significantly longer in the COPD group ( P = 0.02 and P = 0.04), and 30-day mortality was significantly higher in COPD patients (0.8 % vs. 6.1 %, P = 0.03). CONCLUSIONS: COPD increases 30-day mortality, postoperative pulmonary complications, ICU stay and hospital stay. Proper identification and therapy may help to improve outcome in this high-risk population.

Minimized extracorporeal circulation in coronary artery bypass surgery is equivalent to standard extracorporeal circulation in patients with reduced left ventricular function.

BACKGROUND: Minimized extracorporeal circulation (MECC) is a promising alternative to standard extracorporeal circulation (ECC) and its use is increasing in routine coronary bypass surgery. We analyzed the clinical outcome of patients with reduced left ventricular function who underwent coronary artery bypass surgery with MECC or with standard ECC. METHODS: From January 2003 to September 2008, 238 patients with a left ventricular function < 30 % underwent bypass surgery with ECC or MECC. The primary end point of our retrospective observational study was 30-day mortality. Secondary endpoints were the transfusion requirements, as well as intensive care and the in-hospital course. RESULTS: Demographic data, comorbidities and left ventricular function were similar in the study groups. MECC patients had a tendency towards a lower 30-day mortality rate, a better postoperative renal function and reduced ventilation times. Extracorporeal circulation time and postoperative high-dose inotropic support were significantly lower in the MECC group, while the stays in the intensive care unit and in hospital were comparable between the two groups. In our study, age in the ECC group, and previous infarction and New York Heart Association grade IV in the MECC group were preoperative risk factors associated with a higher mortality. CONCLUSION: Coronary bypass surgery using MECC is feasible and safe for patients with severely impaired left ventricular function. It is a promising alternative to ECC with a low mortality rate and a more favorable postoperative course.

[ECMO treatment in acute lung failure : Who profits?] / ECMO-Therapie beim akuten Lungenversagen : Wer profitiert?

In intensive care medicine, rapid technical developments that are often beneficial to patients are taking place. On the other hand, there are also voices that generally criticize an increasing "interventionalism". This area of tension includes other important questions regarding usefulness, quality, ethical compliance, scientific evidence, structural capacities and economy. The treatment of acute respiratory distress syndrome (ARDS) using extracorporeal membrane oxygenation (ECMO) is an example of these considerations. Although ECMO has rarely been prospectively evaluated according to scientific criteria, it is still used with an increasing tendency, not least since the documented register survival rates in ECMO patients with severe ARDS are 60%. However, the implementation of this therapy means an immense effort. The necessary centralization and certification for ECMO treatment is currently under intensive discussion. Closely related to this are considerations about which criteria represent good quality in patient care. In order to be able to guarantee high quality, a precise indication is the first step. And here indications and contraindications still need to be defined. It has not yet been sufficiently clarified which prognosis factors need to be taken into account. This article summarizes what is known about ECMO prognosis and indication criteria. In conclusion, parameters are identified that should be developed scientifically in the future.

Circulating Cell-Free DNA as Inflammatory Marker in Egyptian Psoriasis Patients.

BACKGROUND: Cell lesion and apoptosis with release of cell-free DNA (CFD) in circulation are associated with chronic inflammation of psoriasis. OBJECTIVE: The objective of this study was ï»¿to determine the CFD concentrations in sera of patients with psoriasis, to assess its relationship with disease severity as defined by Psoriasis Area Severity Index (PASI) and other inflammatory biomarkers (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) levels, and to monitor the efficacy of treatment. PATIENTS AND METHODS: Thirty adult patients with different types of psoriasis (25 vulgaris; 10 mild, 15 moderate and 5 erythroderma; severe) were evaluated during the exacerbation phase of the disease, before starting (T0) and after 12 weeks (T12) of treatment with topical therapy for mild cases, narrowband-ultraviolet light B (NB-UVB) for moderate cases and methotrexate for severe cases. Twenty healthy controls were also involved in the study. The concentrations of CFD in sera were measured before and after treatment by quantitative real time PCR (qPCR) using primers of the human ß-globin gene. RESULTS: At T0, all patients presented significant higher levels of ESR (P=0.05) and CFD (P=0.001) compared with controls. Highly significant elevations of all parameters were observed in severe disease (erythroderma) compared to mild/moderate disease (vulgaris). Methotrexate treatment induced highly significant reductions in all inflammatory markers including CFD (P= 0.042) while topical and UV irradiation therapies had no effects. CFD concentrations showed positive correlations with both PASI (r=0.422, P=0.020) and ESR (r=0.321, P=0.023) only before the start of treatment. CONCLUSION: The level of circulating CFD could be used to monitor psoriasis severity. However, its level cannot be stated for the treatment, except in severe erythrodermic patients upon successful treatment with methotrexate. We recommend validation of a convenient and accurate DNA assay applied directly to biological samples which does not require prior DNA extraction and amplification.

Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation.

Long-term survival of lung allografts is limited by chronic rejection (CR). Oxidative stress (OxS) plays a central role in the development of CR. We investigated the influence of pirfenidone (alone or in combination with everolimus) on OxS and CR. A rat model of left lung allo-transplantation (F344-to-WKY) was used to evaluate the effects of pirfenidone alone [0,85% in chow from postoperative day (POD) -3 to 20/60] and in combination with everolimus [2,5 mg/kg bw daily from POD 7 to 20/60]. Allografts of non-treated animals, everolimus treated animals and right, non-transplanted lungs were used as references. Immunohistology of myeloperoxidase (MPO), haemoxygenase-1 (HO-1), iron and platelet-derived-growth-factor-receptor-alpha (PDGFR-a) were performed. On POD 20, all groups showed severe acute rejection (ISHLT A3-4/B1R-B2R). Groups treated with pirfenidone showed a lower interstitial inflammatory infiltration and a lower participation of highly fibrotic degenerated vessels (ISHLT-D2R). In the long term follow up (POD 60), pirfenidone alone significantly reduced chronic airway rejection (ISHLT-C; p≤0.05), interstitial fibrosis (IF; p≤0.05), content of collagen (p≤0.05), expression of PDGFR-a (p≤0.05) and the deposition of iron (p≤0.05). All groups treated with pirfenidone showed a high expression of the cytoprotective enzyme HO-1 (p≤0.05). The additional application of everolimus resulted in a significant decrease of chronic airway rejection (ISHLT-C; p≤0.05), vasculopathy (ISHLT; p≤0.05) and IF (p≤0.05). In conclusion, early application of pirfenidone inhibited the progression of CR by its anti-fibrotic and anti-oxidative properties. The additional application of an m-TOR-inhibitor increased the anti-fibrotic effects of pirfenidone which resulted in a reduction of CR after experimental LTx.