High-Pressure Carbon Monoxide and Oxygen Mixture is Effective for Lung Preservation

Abstract

(1) Background: Heme oxygenase-1 (HO-1) degrades heme and generates carbon monoxide (CO), producing various anti-inflammatory, anti-oxidative, and anti-apoptotic effects. This study aimed to confirm the effects of CO on the ischemia–reperfusion injury (IRI) of donor lungs using a high-pressure gas (HPG) preservation method. (2) Methods: Donor rat and canine lungs were preserved in a chamber filled with CO (1.5 atm) and oxygen (O2; 2 atm) and were ventilated with either CO and O2 mixture (CO/O2 group) or air (air group) immediately before storage. Rat lungs were subjected to heterotopic cervical transplantation and evaluated after reperfusion, whereas canine lungs were subjected to allogeneic transplantation and evaluated. (3) Results: Alveolar hemorrhage in the CO/O2 group was significantly milder than that in the air group. mRNA expression levels of HO-1 remained unchanged in both the groups; however, inflammatory mediator levels were significantly lower in the CO/O2 group than in the air group. The oxygenation of graft lungs was comparable between the two groups, but lactic acid level tended to be higher in the air group. (4) Conclusions: The HO-1/CO system in the HPG preservation method is effective in suppressing IRI and preserving donor lungs.

Transcriptional Regulation of HMOX1 Gene in Hezuo Tibetan Pigs: Roles of WT1, Sp1, and C/EBPα

“…HMOX1 exerts protective effects under stress conditions mainly through the active gas CO and antioxidant bilirubin produced by its decomposition [14,15]. In addition, as a protective gene, HMOX1 has been reported to have protective effects in acute and chronic lung injury such as hyperoxia, hypoxia, ischemia, and hypertension [16][17][18][19]. Although there have been many reports on the structure and function of HMOX1 gene, its transcriptional regulation mechanism has not been fully elucidated.…”

Editorial of Special Issue “Protective and Detrimental Role of Heme Oxygenase-1”

“…The study of Fujiwara et al demonstrated that the physiological effects of the HO-1/CO system were employed for preserving donor lungs with unique characteristics via the high-pressure gas (HPG) preservation method. This approach has significant potential to be used as a new preservation method for lungs [3]. The pharmacological activation of HO-1 activity mimics the effect of caloric restriction (CR), while the HO-1 inhibitor Tin-mesoporphyrin IX (SnMP) increased oxidative stress and cardiac hypertrophy.…”