T. Sandhaus

Impact of preservation solution on the extent of blood-air barrier damage and edema formation in experimental lung transplantation

A major aim in lung transplantation is to prevent the loss of structural integrity due to ischemia and reperfusion (I/R) injury. Preservation solutions protect the lung against I/R injury to a variable extent. We compared the influence of two extracellular‐type preservation solutions (Perfadex, or PX, and Celsior, or CE) on the morphological alterations induced by I/R. Pigs were randomly assigned to sham (n = 4), PX (n = 5), or CE (n = 2) group. After flush perfusion with PX or CE, donor lungs were excised and stored for 27 hr at 4°C. The left donor lung was implanted into the recipient, reperfused for 6 hr, and, afterward, prepared for light and electron microscopy. Intra‐alveolar, septal, and peribronchovascular edema as well as the integrity of the blood‐air barrier were determined stereologically. Intra‐alveolar edema was more pronounced in CE (219.80 ± 207.55 ml) than in PX (31.46 ± 15.75 ml). Peribronchovascular (sham: 13.20 ± 4.99 ml; PX: 15.57 ± 5.53 ml; CE: 31.56 ± 5.78 ml) and septal edema (thickness of alveolar septal interstitium, sham: 98 ± 33 nm; PX: 84 ± 8 nm; CE: 249 ± 85 nm) were only found in CE. The blood‐air barrier was similarly well preserved in sham and PX but showed larger areas of swollen and fragmented epithelium or endothelium in CE. The present study shows that Perfadex effectively prevents intra‐alveolar, septal, and peribronchovascular edema formation as well as injury of the blood‐air barrier during I/R. Celsior was not effective in preserving the lung from morphological I/R injury. Anat Rec, 2007.

Epstein-Barr virus-associated pneumonia and bronchiolitis obliterans syndrome in a lung transplant recipient

We report the case of a 25-year-old lung and liver transplant recipient who developed respiratory failure. High levels of Epstein-Barr virus (EBV) genome copies were detectable in respiratory tract specimens, while the search for various other viral, bacterial or fungal pathogens remained empty. Post-transplant lymphoproliferative disease was excluded. Due to the rapid progression of respiratory insufficiency, a re-transplantation of the lung was performed. EBV-encoded small RNAs could be demonstrated by in situ hybridization within pneumocytes and lymphocytes of the explanted lung tissue. The clinical situation improved soon after re-transplantation, and the EBV load detected in the lower respiratory tract decreased significantly.

Lung retrieval from non-heart-beating donors: First experience with an innovative preservation strategy in a pig Lung transplantation model

Objective: Lung transplantation is limited by the scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. Methods: Heparinized asystolic pigs (n = 5, 30–35 kg) were ventilated for 90 min. The lungs were retrogradely preserved with Perfadex solution and stored inflated at 4°C for 3 h. Left lung transplantation in the recipient was followed by exclusion of the right lung. Results were compared to sham-operated animals. Oxygenation, hemodynamics and dynamic compliance were monitored for 4 h. Infiltration of polymorphonuclear cells (PMNs) and stereological quantification of alveolar edema was performed. Statistical analysis comprised Kruskal-Wallis and Mann-Whitney tests and ANOVA analysis with repeated measures. Results: No mortality was observed. During preservation, continuous elimination of blood clots via the pulmonary artery venting site was observed. Oxygenation and compliance were similar between groups, but sham controls showed significantly lower pulmonary vascular resistance. Stereological quantification revealed higher volume fractions of intra-alveolar edema in NHBD grafts, while PMN infiltration was comparable to sham controls. Conclusions: Use of NHBD lungs results in excellent outcome after 90 min of warm ischemia followed by retrograde preservation with Perfadex solution. This novel approach can optimize lung preservation by eliminating clots from the pulmonary circulation and might clinically be considered in brain-dead organ donors who become hemodynamically unstable prior to organ harvest. Further trials with longer warm and cold ischemic periods are necessary to further elucidate this promising approach to donor pool expansion.

The clinical impact of donor-specific antibodies in heart transplantation

Donor-specific antibodies (DSA) are integral to the development of antibody-mediated rejection (AMR). Chronic AMR is associated with high mortality and an increased risk for cardiac allograft vasculopathy (CAV). Anti-donor HLA antibodies are present in 3-11% of patients at the time of heart transplantation (HTx), with de novo DSA (predominantly anti-HLA class II) developing post-transplant in 10-30% of patients. DSA are associated with lower graft and patient survival after HTx, with one study suggesting a three-fold increase in mortality in patients who develop de novo DSA (dnDSA). DSA against anti-HLA class II, notably DQ, are at particularly high risk for graft loss. Although detection of DSA is not a criterion for pathologic diagnosis of AMR, circulating DSA are found in almost all cases of AMR. MFI thresholds of ~5000 for DSA against class I antibodies, 2000 against class II antibodies, or an overall cut-off of 5-6000 for any DSA, have been suggested as being predictive for AMR. There is no firm consensus on pre-transplant strategies to treat HLA antibodies, or for the elimination of antibodies after diagnosis of AMR. Minimizing the risk of dnDSA is rational but data on risk factors in HTx are limited. The effect of different immunosuppressive regimens is largely unexplored in HTx, but studies in kidney transplantation emphasize the importance of adherence and maintaining adequate immunosuppression. One study has suggested a reduced risk for dnDSA with rabbit antithymocyte globulin induction. Management of DSA pre- and post-HTx varies but typically most centers rely on a plasmapheresis or immunoadsorption, with or without rituximab and/or intravenous immunoglobulin. Based on the literature and a multi-center survey, an algorithm for a suggested surveillance and therapeutic strategy is provided.

Donor heart selection and outcomes: An analysis of over 2,000 cases

BACKGROUNDnDecision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere.nnnMETHODSnThis investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015.nnnRESULTSnOur center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%).nnnCONCLUSIONSnA less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

Low Fibrinogen Is Associated with Increased Bleeding-Related Re-exploration after Cardiac Surgery

Background Re‐exploration after cardiac surgery remains a relatively frequent complication associated with adverse effects on outcome. We aimed to identify risk factors for re‐exploration. Methods We retrospectively reviewed 2,403 patients having undergone cardiac surgical procedure between January 2013 and December 2014. Re‐exploration was required in 114 patients (4.7%). Patients with oral anticoagulation, infective endocarditis, or a clearly identified bleeding source were excluded. Therefore, 42 patients remained for analysis. A matched cohort was selected for age, sex, ejection fraction, creatinine, and procedure out of the non‐re‐explored patients. Results Demographic data were similar in both groups, except for a higher prevalence of diabetes (45 vs. 21%; p = 0.036) in the non‐re‐explored patients. Surgery was elective in two‐thirds and preoperative plasma fibrinogen concentration was lower in patients requiring re‐exploration (2.8 ± 0.9 vs. 3.6 ± 0.9 g/L; p = 0.002). During the initial operation, re‐explored patients received more packed red blood cells (1.5 ± 3 vs. 0 ± 1 units; p < 0.001), Postoperatively, re‐explored patients had higher lactate levels (1.7 ± 1.4 vs. 1.3 ± 0.6 mmol/L, p = 0.044), more chest tube drainage (1,245 ± 948 vs. 685 ± 413 mL; p < 0.001), higher hospital mortality (19 vs. 7%; p = 0.19), and longer intensive care unit (ICU) stays (8 ± 8 vs. 4 ± 7 days; p = 0.010). In addition, more fibrinogen was administrated during the initial surgery. Plasma fibrinogen concentration upon arrival at the ICU was lower in patients requiring re‐exploration (2 ± 0.6 vs. 2.7 ± 0.7 g; p < 0.001). Multivariable linear regression analysis identified fibrinogen upon arrival at the ICU as an independent predictor of postoperative bleeding. Conclusion Cardiac surgery patients with low perioperative plasma fibrinogen concentration appear to be more susceptible to bleeding and re‐exploration. Re‐exploration in this group of patients is associated with increased morbidity and mortality.

Chronic Perforation of the Aortic Arch by Kirschner Wires

Perforation of the heart or great vessels by orthopedic wires is a rare complication that mostly results in severe or even lethal organ injury. Therefore, such conditions mostly require immediate surgical removal of the wires. However, in some individual cases, a conservative approach may be preferable. We describe a case of a 70-year-old woman whose aortic arch has been penetrated by two Kirschner wires used for fixation of a right clavicle fracture 13 years ago. Notably, the complication was an incidental finding during computed tomography angiography for clarification of transient nonspecific neurological symptoms.

Preoperative plasmaphereses plus intraoperative heparin for management of cardiac surgery patients with heparin-induced thrombocytopenia (HIT-II)

Rationale: Heparin-induced thrombocytopenia (HIT) is a drug-induced, immune-mediated type of thrombocytopenia. Its incidence is continuously increasing. HIT poses a tremendous surgical challenge, specifically in cardiothoracic surgery where heparin is the only anticoagulant drug that can be used during cardiopulmonary bypass (CPB) with the possibility of antagonization at the end of surgery. Anticoagulants that are approved for treatment of HIT (lepirudin, argatroban, danaparoid, bivalirudin) are not approved for CPB, and may pose great bleeding risks due to their lack of antagonization. Based on the antibody-mediated nature of the disease, we reasoned that it may be possible to eliminate the HIT antibodies by plasmaphereses immediately preoperatively, allowing heparin and protamin to be used during the main surgical procedure. Objective: We here report our first experience with plasmaphereses in 5 HIT II-positive patients undergoing major cardiothoracic surgery using heparin/protamin. Methods: Three patients underwent heart transplantation, one lung-transplantation and one aortic valve replacement. HIT II was confirmed in all 5 patients and anticoagulant treatment was performed with argatroban until the time of surgery (or until the begin of plasmaphereses). The transplant patients received a single run of plasmaphereses for 3 – 5 hours immediately after the donor organ was accepted and before transplantation. The patient requiring aortic valve replacement received two episodes of plasmaphereses and a postprocedural verification that HIT antibodies had been eliminated. The surgical procedure was performed using standard heparin/protamin. Postopoerative anticoagulation was again achieved with argatroban according to standard protocol. Results: All patients survived the operation and are still alive. There were no complications or side effects during the plasma exchange. The use of heparin during the transplantation or valve replacement was free of complications. No thromboembolic or bleeding complications were observed. Conclusions: The results suggest that preoperative plasma exchange to eliminate circulating HIT-II antibodies in HIT-II positive patients and using heparin during a major cardiothoracic procedure is safe. The technique may allow a safer and technically easier treatment of a continuously growing group of patients, specifically transplant patients. However, more experience is needed to verify this suggestion.