Transient hyperthermia during ex vivo lung perfusion has no protective effect in rat model

• Published in: Transplant immunology Vol. 77; p. 101800
• Main Authors: Park, Soo Jin, Suh, Jee Won, Haam, Seokjin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2023
• Subjects: Animals; Cytokines; Ex vivo lung perfusion; Heat shock protein; Hyperthermia, Induced; Ischemic reperfusion injury; Lung - physiology; Lung Transplantation; Male; Perfusion - methods; Rats; Rats, Sprague-Dawley; Transcriptome; Transient hyperthermia; Ischemic reperfusion injury; Transient hyperthermia; Ex vivo lung perfusion; Lung transplantation; Heat shock protein; Transcriptome
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2023.101800

Although ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation, EVLP itself can lead to inflammation in the lung. Heat shock proteins (HSPs) have anti-inflammatory effects and can reduce ischemic reperfusion injury in the donor's lungs after transplantation. In this study, the effects of transient hyperthermia during EVLP on the expression of HSPs and inflammatory pathways were examined.
Fifteen male Sprague–Dawley rats were randomly divided into three groups: sham (n = 5), normothermic EVLP (37 °C, n = 5), and transient hyperthermia during EVLP (42 °C, n = 5). Lung function analyses regarding PaO2/FiO2 ratio, compliance, and pulmonary vascular resistance were conducted. The expression levels of HSPs and inflammatory cytokines were also evaluated. The degree of lung injury was histopathologically evaluated. Transcriptome analysis was performed on lung tissues from the sham (n = 2), normothermic EVLP (n = 2), and heat stress-EVLP (n = 2) groups.
There were no significant differences in functional or histological parameters between the three groups. The expression of HSPs had significantly increased, especially that of HSPs 40 and 60 in the heat stress EVLP group; this was consistent with the inflammatory response. Inflammatory cytokine levels were significantly higher during EVLP and intensified with transient hyperthermia.
Transient hyperthermia during EVLP has no protective effect on the donor lung graft or activation of the inflammatory pathway at the gene level.
•Normothermic perfusate is used during ex vivo lung perfusion (EVLP).•The effects of transient hyperthermia during EVLP are unknown.•Transient hyperthermia affects the expression of heat shock proteins and cytokines.•Transient hyperthermia does not affect the function or histology of procured lungs.•Targets to protect against ischemic reperfusion injury need to be investigated.