The pulmonary donor pool would increase substantially if lungs could be donated after cardiac death (DCD). There have been ethical and legal obstacles since administration of heparin and cooling has to be done immediately after cardiac death. This study examines whether ventilation of DCD lungs without administering heparin or cooling the lungs after cardiac death could improve graft function.Twelve donor pigs with a mean bodyweight of 70 kg were randomized into two groups. Six animals were ventilated in situ with 50% oxygen, 4 L/min, and 5 cm H2O in positive end-expiratory pressure or PEEP for 2 h after cardiac death. Six animals served as non-ventilated controls and were exposed to warm ischemia for 2 h. After 2 h, all lungs were harvested and flush perfused with Perfadex(®) solution and stored at 8°C for another 2 h. An ex vivo lung perfusion or EVLP circuit was used for evaluation.Non-ventilated lungs developed pulmonary edema, and had highly impaired blood gas levels and a significantly increased weight. The ventilated lungs demonstrated excellent blood gas levels and unchanged weight.The increase in tolerable warm ischemic time in combination with avoiding heparinization and cooling might facilitate the use of DCD lungs for transplantation.
Background: The method of ex vivo lung perfusion (EVLP) has been suggested as a reliable means of differentiating between “good” and “poor” pulmonary grafts in marginal donors as, when grafts identified as good by this method are transplanted, the results do not differ from those using lungs fulfilling standard criteria. The EVLP method is also thought to improve pulmonary grafts by reducing lung edema and eliminating lung atelectasis. In the present study, we investigated whether the pulmonary graft could be further improved by extending the duration of EVLP. Methods and Materials: Six Landrace pigs were used. The lungs were reconditioned and evaluated, using the EVLP method, as double lungs. After the initial evaluation, EVLP was continued for a further 90 minutes. Results: The arterial oxygen level (pO 2 ) was 60.8 ± 4.8 kPa after the standard 60 minutes of EVLP and 67.1 ± 2.2 kPa after 150 minutes (p = 0.48). The pulmonary vascular resistance was 453 ± 78 dyne*s/cm 5 after 60, 90, 120 and 150 minutes of EVLP (p = 1.0). The pulmonary artery pressure was 17.8 ± 1.0 mmHg after 60, 90, 120, and 150 minutes of EVLP (p = 1.0) and the pulmonary artery flow was 3.5 ± 0.4 l/min after 60, 90, 120, and 150 minutes of EVLP (p = 1.0). The mean weight of the pulmonary grafts after harvesting was 574 ± 20 g at the beginning of EVLP 541 ± 24 g and, after 150 min of EVLP, 668 ± 33 (p = 0.011). Conclusions: The blood gases and hemodynamic parameters in the pulmonary grafts did not improve as a result of the extra 90 minutes of EVLP. However, the weight of the pulmonary graft increased significantly with increasing duration of EVLP, indicating lung perfusion injury.
In recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. In addition, using such therapies in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post-transplantation. However, the mechanism by which this therapy improves the donor lung on a molecular basis is not yet fully understood.We hypothesized that there were characteristic inflammatory and immunomodulatory differences between the lungs treated with and without cytokine adsorption, reflecting proteomic changes in the gene ontology pathways and across inflammation-related proteins. In this study, we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts lung function when used during EVLP and post-transplantation as hemoperfusion in a porcine model. Lung tissues during EVLP and post-lung transplantation were analyzed for their proteomic profiles using mass spectrometry.We found through gene set enrichment analysis that the inflammatory and immune processes and coagulation pathways were significantly affected by the cytokine treatment after EVLP and transplantation.In conclusion, we showed that the molecular mechanisms are using a proteomic approach behind the previously reported effects of cytokine adsorption when compared to the non-treated transplant recipients undergoing EVLP.
The risk of adults with a congenital heart defect (ACHD) developing heart failure, stroke, arrhythmias, and the need for valve replacement is increased compared to healthy peers. Evidence for the use of novel oral anticoagulants (NOAC) in this patient group is still lacking and vitamin K antagonists (VKA) are the primary choice for patients with a mechanical valve. The present aim was to determine the rate of thromboembolic and major bleeding events in ACHD patients on VKA therapy. This was a retrospective study on ACHD patients on VKA treatment registered in the National Quality Registry for Congenital Heart Disease, SWEDCON, and Atrial fibrillation and Anticoagulation, AuriculA, from Southern Sweden. 213 patients were included with a mean age of 50 years (±18) years and a mean follow-up of 6.6 years (±3.3 years), 16% had complex defects and 41% had valvular VKA therapy indication. In total, 34 complications were registered, of which 14 were thromboembolic events and 20 were major bleeding events. The rate of thromboembolism and major bleeding events was 1.0 (95% CI: 0.6–1.6) and 1.4 (95% CI: 0.9–2.2) per 100 patient-years, respectively. Forty-three patients died during the study period. The mortality rate was 3.1 per 100 patient-years (95% CI: 2.2–4.1). We found a low rate of thromboembolic events and major bleeding events for low-moderate risk ACHD patients with good quality of VKA anticoagulation. The target of TTR>65% for ACHD patients is recommended.
Background. There are increasing reports of serious complications and deaths associated with negative pressure wound therapy (NPWT). Bleeding may occur when NPWT is applied to a wound with exposed blood vessels. Inserting a rigid disc in the wound may protect these structures. The authors examined the effects of rigid discs on wound bed tissue pressure and blood flow through a large blood vessel in the wound bed during NPWT. Methods. Wounds were created over the femoral artery in the groin of 8 pigs. Rigid discs were inserted. Wound bed pressures and arterial blood flow were measured during NPWT. Results. Pressure transduction to the wound bed was similar for control wounds and wounds with discs. Blood flow through the femoral artery decreased in control wounds. When a disc was inserted, the blood flow was restored. Conclusions. NPWT causes hypoperfusion in the wound bed tissue, presumably as a result of mechanical deformation. The insertion of a rigid barrier alleviates this effect and restores blood flow.
Background: A subgroup of COPD patients (pts) displays eosinophilia, a trait targeted in several clinical drug programs. Little is known about the mechanisms underlying eosinophil (eos) infiltration into COPD lungs, or how eos infiltration relates to microbial presence and immune cell composition. Aims: Reveal the spatial relationship between tissue eos, microbes, and immune cell patterns in lungs and lymph nodes from COPD pts. Methods: Surgical lung tissue was collected from 35 COPD pts (GOLD I-IV) and 17 non-COPD controls. Microbes and complete immune cell profiles were identified histologically by combined in situ hybridization and multiplex immunohistochemistry, followed by computerized spatial analysis. Results: Mean total tissue eos increased in severe COPD. The infiltration pattern was patchy with no spatial correlation to bacteria, viruses, or fungi. Multiplex imaging of major leukocyte and structural cell populations revealed spatially distinct immune cell niches in which eos-rich microenvironments occurred alongside neutrophil- and macrophage-dominated regions. Eos and type 2 foci were spatially linked to basophils, CD20+ B lymphocytes, CD20-CD19+ plasmablasts, and CD138+ plasma cells. Eos infiltration in bronchi, small airways, or alveolar regions was associated with eosinophilia in the subcapsular and medullary lymphatic sinuses in lung-draining lymph nodes. Conclusions: Patchy eosinophilia was linked to adaptive immune niches that with spatially separated non-eos inflammation yields complex mixed inflammatory signatures that likely impact treatment response. The finding of no spatial association between microbial presence and eosinophilia suggests that other non-infectious factors are involved.
Abstract There are increasing reports of deaths and serious complications associated with the use of negative pressure wound therapy ( NPWT ). Bleeding may occur in patients when NPWT is applied to a wound with exposed blood vessels or vascular grafts, possibly due to mechanical deformation and hypoperfusion of the vessel walls. Recent evidence suggests that using a rigid barrier disc to protect underlying tissue can prevent this mechanical deformation. The aim of this study was to examine the effect of rigid discs on the tissue exposed to negative pressure with regard to tissue pressure and microvascular blood flow. Peripheral wounds were created on the backs of eight pigs. The pressure and microvascular blood flow in the wound bed were measured when NPWT was applied. The wound was filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. The discs were created with or without channels (to accommodate exposed sensitive structures such as blood vessels and nerves), perforations, or a porous dressing that covered the underside of the discs (to facilitate pressure transduction and fluid evacuation). When comparing the results for pressure transduction to the wound bed, no significant differences were found using different discs covered with dressing, whereas pressure transduction was lower with bare discs. Microvascular blood flow in the wound bed decreased by 49 ± 7% when NPWT was applied to control wounds. The reduction in blood flow was less in the presence of a protective disc (e.g., −6 ± 5% for a dressing‐covered, perforated disc, p = 0.006). In conclusion, NPWT causes hypoperfusion of superficial tissue in the wound bed. The insertion of a rigid barrier counteracts this effect. The placement of a rigid disc over exposed blood vessels or nerves may protect these structures from rupture and damage.
