ArticleXenotransplantation2019
Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood.
Article in Xenotransplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Pig-to-human lung xenotransplantation into a brain-dead recipient.Nature medicine · 2025Article
- Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Future of Lung Transplantation: Xenotransplantation and Bioengineering Lungs.Clinics in chest medicine · 2023Review
- Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs.Xenotransplantation · 2022Article
- Human erythrocyte fragmentation during ex-vivo pig organ perfusion.Xenotransplantation · 2022Article
- hEPCR.hTBM.hCD47.hHO-1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood.Xenotransplantation · 2022Article
- Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.Xenotransplantation · 2021Article
- Differences in platelet aggregometers to study platelet function and coagulation dysregulation in xenotransplantation.Xenotransplantation · 2021Review
- Minimizing Ischemia Reperfusion Injury in Xenotransplantation.Frontiers in immunology · 2021Review
- Xenotransplantation of the Porcine Lung-From Immunological Barriers to Emerging Experimental Strategies.XenotransplantationReview
- Article
- Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood.XenotransplantationArticle
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundElevated pulmonary vascular resistance (PVR), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on PVR, and their contribution to other lung xenograft injury mechanisms.
methodsGalTKO.hCD46 single pig lungs were perfused ex vivo with fresh heparinized human blood: lungs were either treated with 1-Benzylimidazole (1-BIA) combined with histamine receptor blocker famotidine (n = 4) or diphenhydramine (n = 6), 1-BIA alone (n = 6) or were left untreated (n = 9).
resultsSix of the nine control experiments (GalTKO.hCD46 untreated), "survived" until elective termination at 4 hours. Without treatment, initial PVR elevation within the first 30 minutes resolved partially over the following hour, and increased progressively during the final 2 hours of perfusion. In contrast, 1-BIA, alone or in addition to either antihistamine treatment, was associated with low stable PVR. Combined treatments significantly lowered the airway pressure when compared to untreated reference. Although platelet and neutrophil sequestration and coagulation cascade activation were not consistently altered by any intervention, increased terminal wet/dry weight ratio in untreated lungs was significantly blunted by combined treatments.
conclusionCombined thromboxane and histamine pathway blockade prevents PVR elevation and significantly inhibits loss of vascular barrier function when GalTKO.hCD46 lungs are perfused with human blood. Platelet activation and platelet and neutrophil sequestration persist in all groups despite efficient complement regulation, and appear to occur independent of thromboxane and histamine antagonism. Our work identifies thromboxane and histamine as key mediators of xenolung injury and defines those pathways as therapeutic targets to achieve successful xenolung transplantation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.