29. SUBSTRATE METABOLISM IN THE PRESERVED RAT LUNG: A 13C NMR STUDY
Paul E. Meyer, Michael E. Jessen, Jayendra B. Patel, Robert Y. Chao, Craig R. Malloy, Dan M. Meyer
UT Southwestern Medical Center at Dallas
Dallas, Texas, USA
BACKGROUND
Lung transplantation requires a period of ischemia, but effects on intermediary metabolism are unknown and may be important to preservation strategies.
MATERIAL AND METHODS
Two groups (n=16 each) of isolated rat lung blocks were flushed with EuroCollins via the pulmonary artery and then harvested. Lung blocks were ventilated (40% FIO2) and perfused at 20 mL/min for 30 min with an erythrocyte-based Krebs solution containing physiologic levels of lactate, pyruvate, acetoacetate, mixed fatty acids, and glucose labeled with 13C to yield specific forms of acetyl-CoA. Group 1 was perfused immediately after harvest while Group 2 was stored for 6 hours (1 degree Celsius), then perfused for 30 minutes. Half of each group was perfused at a physiologic pO2 (43
± 8 mmHg) while the other half was perfused at high pO2 (614 ± 6mmHg). After perfusion, lungs were freeze-clamped and extracted. 13C spectra were obtained in a 9.4T Bruker spectrometer. Substrate oxidation patterns were determined by isotopomer analysis.RESULTS
Aerobic metabolism requires entry of acetyl-CoA into the citric acid cycle. The percentage of acetyl-CoA arising from each substrate is shown in the Table.
|
Group |
Acetoacetate |
Lactate/Pyruvate |
Fatty Acids |
Glucose/Endogenous |
|
1 |
11.5 ± 1.4 |
11.1 ± 0.9 |
22.0 ± 2.1 |
55.4 ± 3.9 |
|
2 |
14.6 ± 1.4 |
11.8 ± 1.2 |
31.3 ± 2.2= |
42.2 ± 3.7= |
Data are Mean
± SE; n=16 each group; = =P<0.05 between groups by one-way ANOVACONCLUSION
Lungs metabolize all major substrates, even after ischemia. Subset analysis found no effect of perfusate pO2 on metabolism. After storage, fatty acid (FA) oxidation was increased at the expense of either glucose or endogenous energy stores. As high FA oxidation after ischemia is deleterious in other organs, strategies to suppress FA oxidation may warrant investigation for lung preservation.
