Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system

Area of Science:

• Cardiovascular and Respiratory Physiology
• Transplantation Immunology
• Organ Preservation and Perfusion

Background:

• Brain death (BD) leads to endothelin axis upregulation, causing inflammation and lung graft damage.
• Tezosentan, an endothelin receptor blocker, can improve hemodynamics but may cause systemic side effects.
• Ex vivo lung perfusion (EVLP) offers a platform for organ-specific resuscitation to enhance donor lung quality.

Purpose of the Study:

• To investigate the efficacy of combining EVLP with tezosentan administration in improving donor lung quality.
• To assess the impact of this combined therapy on pulmonary gas exchange and lung injury in a 6-hour ovine model of brain stem death (BSD).

Main Methods:

• Twelve sheep underwent 6 hours of BSD, with lungs allocated to control or tezosentan-treated EVLP groups.
• Lungs were perfused for 6 hours, with perfusate and tissue samples analyzed for blood gases, proteins, and inflammatory biomarkers (IL-6, IL-8).
• Histology and wet-dry weight ratio were used to assess lung injury and edema.

Main Results:

• Tezosentan-treated lungs demonstrated significantly improved gas exchange, with higher partial pressure of oxygen and lower partial pressure of carbon dioxide.
• Histological analysis revealed minimal lung injury, with no significant differences between the control and tezosentan groups.
• Pro-inflammatory cytokine levels (IL-6, IL-8) and wet/dry weight ratio showed no significant differences between the groups.

Conclusions:

• Administration of tezosentan during EVLP can enhance pulmonary gas exchange in donor lungs.
• The combination of EVLP and tezosentan shows promise for improving donor lung quality without inducing significant additional lung injury or inflammation.