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Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake.

American journal of physiology. Lung cellular and molecular physiology (2015-06-28)
Brian B Graham, Rahul Kumar, Claudia Mickael, Linda Sanders, Liya Gebreab, Kendra M Huber, Mario Perez, Peter Smith-Jones, Natalie J Serkova, Rubin M Tuder
ABSTRACT

In severe pulmonary hypertension (SPH), prior studies have shown an increase in right ventricle (RV) uptake of glucose, but it is unclear whether there is a change in the relative utilization of fatty acids. We hypothesized that in the RV in SPH, as in left ventricular (LV) failure, there is altered substrate utilization, with increased glucose uptake and decreased fatty acid uptake. SPH was induced in rats by treatment with the VEGF receptor inhibitor SU5416 and 3 wk of hypoxia (10% FiO2 ), followed by an additional 4 wk of normoxia (SU-Hx group). Control rats were treated with carboxymethylcellulose vehicle and 7 wk of normoxia (CMC-Nx group). The rodents then underwent positron emission tomography with sequential administration of two radiotracers, 2-deoxy-2-[(18)F]fluoroglucose ((18)F-FDG) and 14-(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)F-FTHA), analogs of glucose and fatty acid, respectively. Five CMC-Nx and 3 SU-Hx rats completed the entire experimental protocol. In the RV, there was a mild increase in (18)F-FDG uptake (1.35-fold, P = 0.085) and a significant decrease in (18)F-FTHA uptake (-2.1-fold, P < 0.05) in the SU-Hx rats relative to the CMC-Nx rats. In the LV, SU-Hx rats had less uptake of both radiotracers compared with CMC-Nx rats. Less RV fatty acid uptake in SPH was corroborated by decreased fatty acid transporters and enzymes in the RV tissue, and specifically a decrease in lipoprotein lipase. In the RV in rats with SPH, there is a major shift in metabolic substrate preference, largely due to decreased fatty acid uptake.

MATERIALS
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Brand
Product Description

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Tris(tert-butoxy)silanol, packaged for use in deposition systems
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Tris(tert-butoxy)silanol, 99.999%
Tantalum(V) ethoxide, packaged for use in deposition systems
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Tantalum(V) ethoxide, 99.98% trace metals basis