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Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system
- Source :
- Journal of Biomedical Science, Journal of Biomedical Science, Vol 27, Iss 1, Pp 1-9 (2020)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Background A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). Methods After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). Results Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin–eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. Conclusions These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.
- Subjects :
- Endothelin Receptor Antagonists
Resuscitation
medicine.medical_specialty
Pyridines
Vasodilator Agents
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Clinical Biochemistry
Urology
lcsh:Medicine
Tetrazoles
Hemodynamics
030204 cardiovascular system & hematology
030230 surgery
EVLP
03 medical and health sciences
0302 clinical medicine
Tezosentan
medicine
Animals
Lung transplantation
Pharmacology (medical)
Endothelin axis
Lung
Molecular Biology
Sheep, Domestic
Endothelin receptor antagonist
business.industry
Research
lcsh:R
Biochemistry (medical)
Histology
Cell Biology
General Medicine
respiratory system
Tissue Donors
respiratory tract diseases
Respiratory Function Tests
Perfusion
Disease Models, Animal
Brain stem death
medicine.anatomical_structure
business
Endothelin receptor
medicine.drug
Subjects
Details
- ISSN :
- 14230127
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Biomedical Science
- Accession number :
- edsair.doi.dedup.....26725a08083858505995286344580aad