Effects of storage and reperfusion oxygen content on substrate metabolism in the isolated rat lung

BACKGROUND: Lung transplantation requires a period of storage and ischemia; we examined the largely unknown effects of that period on intermediary metabolism. METHODS: Two groups of isolated rat lung blocks (n = 16 each) were flushed with Euro-Collins solution and harvested. The lung blocks were immediately ventilated and either perfused for 30 minutes with an erythrocyte-based solution containing carbon 13 labeled substrates (group 1) or stored for 6 hours at 1 degree C and then reperfused (group 2). Half of each group was reperfused at a physiologic Po2 the other half at high Po2. Analysis of carbon 13 isotopomers was performed to determine substrate utilization through aerobic pathways in lung tissue. RESULTS: Lungs from both groups oxidized all major substrates. The contribution of fatty acids to acetylcoenzyme acid oxidized in the citric acid cycle was significantly higher in group 2 than in group 1 (31.3% +/- 2.2% versus 22.0% +/- 2.1%, p < 0.05). Perfusate Po2 did not affect substrate preference. Gas exchange was worse in stored lungs. CONCLUSIONS: After a period of hypothermic ischemia and storage, substrate preference in lung tissue exhibits a switch towards fatty acids. As fatty acid oxidation occurring after ischemia is deleterious in other organs, strategies to inhibit this process in stored lungs may warrant further investigation.