Therapeutic Effects of Argon Inhalation on Lung Ischemia-Reperfusion Injury in CLAWN Miniature Swine

Background: Noble gases, such as argon, have been observed to exhibit cytoprotective effects. The non-anesthetic properties, abundance, and cost-effectiveness of argon suggest its clinical potential. While its efficacy in mitigating ischemia-reperfusion injury has been demonstrated in cellular and small animal models, data on its effects in large animals remain limited. This study evaluated the effects of argon inhalation on pulmonary ischemia-reperfusion injury in miniature swine with potential applications in transplantation. Methods: The left bronchial and pulmonary artery and veins were clamped for 90 min, and then the clamps were released to induce lung ischemia-reperfusion injury in 10 CLAWN miniature swine. The argon group (n = 5) inhaled a mixture of 30% oxygen and 70% argon for 360 min, whereas the control group (n = 5) inhaled a mixture of 30% oxygen and 70% nitrogen for an equivalent duration. Lung function was evaluated using chest X-ray, lung biopsies, and blood gas analysis. Results: The PaO₂/FiO₂ ratio significantly decreased in the control group 2 h post-reperfusion (568 ± 12 to 272 ± 39 mmHg), but was better preserved in the argon group (562 ± 17 to 430 ± 48 mmHg). Blood gas from the left pulmonary vein showed a superior PvO₂/FiO₂ ratio in the argon group (331 ± 40 vs. 186 ± 17 mmHg at 2 h; 519 ± 19 vs. 292 ± 33 mmHg at 2 days). Chest X-ray revealed reduced infiltration in the left lung. The lung biopsy histological scores improved in the argon group at 2 h and 2 days. Serum superoxide dismutase analysis and tissue TUNEL assays suggested that antioxidant and anti-apoptotic mechanisms, respectively, were involved. Conclusions: Perioperative argon inhalation attenuates ischemia-reperfusion injury in swine lungs, likely via anti-apoptotic and antioxidant effects.