lung reconditioning

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled...

Lung transplantation remains the only curative treatment for end stage pulmonary disease. Lung ischemia-reperfusion injury (IRI) is a major contributor to primary allograft dysfunction and donor organ non-utilization. The alveolar macrophage is a key inflammatory mediator in IRI. Ex vivo lung perfusion (EVLP) has been investigated to rehabilitate lungs prior to transplant but has failed to provide significant improvements after IRI. We hypothesized that liquid ventilation could be utilized for ex vivo lung reconditioning in a rat IRI model...

Lung transplantation is the most effective therapy for patients with end-stage lung disease. However, concern of donor lung damage and ischemia-reperfusion induced lung injury limits the use of "marginal" donor lungs. Recent transcriptomic studies have demonstrated that the enrichment of gene-clusters related to cell death and inflammation are the most profound signals during ischemia-reperfusion in human lung transplants. Herein, we focus on the relationship between inflammation and programmed cell death, especially necroptosis, mitochondrial permeability transition-initiated regulated necrosis, pyroptosis, ferroptosis, and autophagic cell death...

Background: Ex vivo lung perfusion (EVLP) may allow therapeutic reconditioning of damaged lung grafts before transplantation. This study aimed to develop relevant rat models of lung damage to study EVLP therapeutic reconditioning for possible translational applications. Methods: Lungs from 31 rats were exposed to cold ischemia (CI) or warm ischemia (WI), inflated at various oxygen fractions (FiO2 ), followed by 3 h EVLP. Five groups were studied as follow: (1) C21 (control): 3 h CI (FiO2 0...

Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population, older donors are increasingly considered. Donor age, at the same time has been linked to higher rates of lung ischemia reperfusion injury (IRI). This process of acute, sterile inflammation occurring upon reperfusion is a key driver of primary graft dysfunction (PGD) leading to inferior short- and long-term survival. Understanding and improving the condition of older lungs is thus critical to optimize outcomes...

PURPOSE OF REVIEW: Significant limitations in organ availability and postoperative graft dysfunction plague lung transplantation and there is continual need for innovation. Ex-vivo lung perfusion (EVLP) has emerged over the last decade as an alternative and/or complementary allograft storage and assessment tool, however logistical hurdles have limited its widespread dissemination. As such, the overall current and potential value of EVLP on modern-day lung transplantation should be considered as innovation moves forward...

An increased focus on improving efficiency and decreasing costs has resulted in alternative models of donor management and organ recovery. The specialized donor care facility model provides highly efficient and cost-effective donor care at a free-standing facility, resulting in improved organ yield, shorter ischemic times, decreased travel, and fewer nighttime operations. Ex vivo lung perfusion (EVLP) improves utilization of extended criteria donor lungs, and centralized EVLP facilities have the potential to increase transplant volumes for smaller transplant programs in specified geographic regions...

Lung transplantation is a life-saving treatment for patients with end stage lung disease. The imbalance between lung graft supply and recipients has been a serious issue and barrier to successful lung transplantation. Ex vivo lung perfusion is a strategy wherein lungs are perfused and ventilated outside of the body. This technology has emerged as a safe preservation method that also enables the reassessment and reconditioning of marginal lung grafts. Ex vivo lung perfusion has successfully expanded the donor pool and led to greater lung transplant activity worldwide...

Although short-term machine perfusion (≤24 h) allows for resuscitation and viability assessment of high-risk donor livers, the donor organ shortage might be further remedied by long-term perfusion machines. Extended preservation of injured donor livers may allow reconditioning, repairing, and regeneration. This review summarizes the necessary requirements and challenges for long-term liver machine preservation, which requires integrating multiple core physiological functions to mimic the physiological environment inside the body...

BACKGROUND: The number of patients waiting for a lung transplant worldwide greatly exceeds the number of available donors. Ex vivo lung perfusion is a useful tool that allows marginal donor lungs to be evaluated and reconditioned for a successful lung transplantation. AIM: To describe the first Chilean and Latin American experience in ex vivo lung perfusion for marginal donor lungs before transplantation. MATERIAL AND METHODS: Descriptive analysis of all ex vivo lung perfusion conducted for marginal donor lungs at a private clinic, from April 2019 to October 2020...

PURPOSE: This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients. MATERIALS AND METHODS: Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen...

BACKGROUND: Warm ischemia followed by blood reperfusion is associated with reduced myocardial contractility. Circulatory death (CD) hearts are maintained by machine perfusion (MP) with blood. However, the impact of MP with histidine-tryptophane-ketoglutarate (HTK) or novel HTK-N solution on reconditioning of CD-heart contractility is unknown. METHODS: In a porcine model, native hearts were directly harvested (control), or CD was induced before harvesting, followed by left ventricular (LV) contractile assessment...

Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated...

PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is a devastating complication in the acute postoperative lung transplant period, associated with high short-term mortality and chronic rejection. We review its definition, pathophysiology, risk factors, prevention, treatment strategies, and future research directions. RECENT FINDINGS: New analyses suggest donation after circulatory death and donation after brain death donors have similar PGD rates, whereas donors >55 years are not associated with increased PGD risk...

PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is a devastating complication in the acute postoperative lung transplant period, associated with high short-term mortality and chronic rejection. We review its definition, pathophysiology, risk factors, prevention, treatment strategies, and future research directions. RECENT FINDINGS: New analyses suggest donation after circulatory death and donation after brain death donors have similar PGD rates, whereas donors >55 years are not associated with increased PGD risk...

The increasing use of marginal lungs for transplantation encourages novel approaches to improve graft quality. Melanocortins and their receptors (MCRs) exert multiple beneficial effects in pulmonary inflammation. We tested the idea that treatment with the synthetic α-melanocyte-stimulating hormone analogue [Nle4,D-Phe7]-α-MSH (NDP-MSH) during ex-vivo-lung-perfusion (EVLP) could exert positive influences in lungs exposed to different injuries. Rats were assigned to one of the following protocols (N = 10 each): 1) ischemia/reperfusion (IR) or 2) cardiac death (CD) followed by ex-vivo-perfusion...

BACKGROUND: Normothermic ex vivo lung perfusion (EVLP) allows for functional assessment of donor lungs; thus has increased the use of marginal lungs for transplantation. To extend EVLP for advanced organ reconditioning and regenerative interventions, cellular metabolic changes need to be understood. We sought to comprehensively characterize the dynamic metabolic changes of the lungs during EVLP, and to identify strategies to improve EVLP. METHODS: Human donor lungs (n = 50) were assessed under a 4-hour Toronto EVLP protocol...

KRASG12C inhibitors, including MRTX849, are promising treatment options for KRAS-mutant non-small cell lung cancer (NSCLC). PD-1 inhibitors are approved in NSCLC; however, strategies to enhance checkpoint inhibitor therapy (CIT) are needed. KRASG12C mutations are smoking-associated transversion mutations associated with high tumor mutation burden, PD-L1 positivity, and an immunosuppressive tumor microenvironment. To evaluate the potential of MRTX849 to augment CIT, its impact on immune signaling and response to CIT was evaluated...

Lung bioengineering has emerged to resolve the current lung transplantation limitations and risks, including the shortage of donor organs and the high rejection rate of transplanted lungs. One of the most critical elements of lung bioengineering is bioreactors. Bioreactors with different applications have been developed in the last decade for lung bioengineering approaches, aiming to produce functional reproducible tissue constructs. In this paper, the current status and advances made in the development and application of bioreactors for bioengineering lungs are comprehensively reviewed...

INTRODUCTION: Ex vivo lung perfusion (EVLP) is an established technique to evaluate and eventually recondition lungs prior to transplantation. Custodiol-MP (C-MP) solution is a new solution, designed for clinical machine perfusion, that has been used for kidneys. The aim of this study was to compare the effects of EVLP with Custodiol-MP on lung functional outcomes to the gold standard of EVLP with Steen Solution™. MATERIAL AND METHODS: In a porcine EVLP model of DCDD (Donation after Circulatory Determination of Death), lungs were perfused with Steen Solution™ (SS, n  = 7) or Custodiol-MP solution supplemented with 55 g/l albumin (C-MP, n  = 8)...