Shuttling of intermediary metabolites such as lactate and pyruvate contribute to the dynamic energy needs of tissues. Tracer kinetic studies offer a powerful method to measure the metabolism of substrates like lactate and pyruvate that are simultaneously taken up from and released into the circulation by organs. We examined the transpulmonary lactate and pyruvate kinetics in an anesthetized rat model during an unstimulated (Con), lactate clamp (LC) and epinephrine infusion (Epi) using a primed-continuous infusion of [U-13C]lactate and pyruvate. Compared to Con and Epi stimulation, LC significantly increased mixed central venous ([v]) and arterial ([a]) pyruvate and lactate concentrations (P < 0.05). Transpulmonary net lactate and pyruvate balances were positive during all three conditions indicating net metabolite uptake. Net balance was significantly greater during epinephrine stimulation compared to the unstimulated control for both lactate and pyruvate (P < 0.05). Tracer measured lactate fractional extractions were similar for unstimulated and lactate clamp conditions, but negative during Epi stimulation when a transpulmonary production of lactate from venous pyruvate occurred. Tracer measured pyruvate fractional extraction averaged 42.8 ± 5.8% for all three conditions, and was significantly higher during epinephrine stimulation (P < 0.05) than during either Con or LC conditions, which did not significantly differ from each other. Lactate total release (= tracer measured uptake − net release) increased due to a lactate load (i.e., LC) and decreased (i.e., negative) from epinephrine stimulation because of the transpulmonary pyruvate to lactate conversion. Pyruvate total release was significantly higher during epinephrine stimulation (400 ± 100 µg/min) vs. Con (30 ± 20 µg/min) (P < 0.05). For lactate, we conclude that transpulmonary concentration difference measurements across the lungs provide an incomplete—and perhaps misleading—picture of parenchymal lactate metabolism, especially during epinephrine stimulation. Regarding pyruvate, significant extraction occurs during circulatory transport across the lungs. The extent of pulmonary parenchymal pyruvate extraction predicts high expression of monocarboxylate (lactate/pyruvate) transporters (MCTs) in the tissue and western blot analysis of whole lung homogenates detected three isoforms: MCT1, MCT2, and MCT4. We conclude that a critical site of circulating pyruvate extraction resides in the lungs. Furthermore, during times of elevated circulating pyruvate or epinephrine stimulation, pyruvate extraction increases.
|Advisor:||Brooks, George A.|
|Commitee:||Lehman, Steven L., Machen, Terry E.|
|School:||University of California, Berkeley|
|School Location:||United States -- California|
|Source:||DAI-B 72/11, Dissertation Abstracts International|
|Keywords:||Lung, Metabolism, Pulmonary, Pyruvate, Transpulmonary lactate|
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