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

Abstract

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°C and then reperfused (group 2). Half of each group was reperfused at a physiologic P o 2 the other half at high P o 2. 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 acetyl-coenzyme 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 P o 2 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.