Pyruvate-modified perfadex improves lung function after long-term hypothermic storage

Background: Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function. Methods: Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10°C containing either 5 mmol/liter uniformly carbon-13 (U-¹³C) labeled glucose (Perfadex), 32 mmol/liter 3-¹³C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of ¹³C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused. Results: Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p < 0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p < 0.05). Conclusions: Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.