Treatment Response of Ethyl Pyruvate in a Mouse Model of Chronic Obstructive Pulmonary Disease Studied by Hyperpolarized 129Xe MRI

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Abstract

Purpose:

The purpose of this work was to investigate disease progression and treatment response in a murine model of chronic obstructive pulmonary disease (COPD) using a preclinical hyperpolarized 129Xe (HPXe) magnetic resonance imaging (MRI) strategy.

Methods:

COPD phenotypes were induced in 32 mice by 10 weeks of exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). Efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, was investigated by administering EP to 16 of the 32 mice after 6 weeks of CS and LPS exposure. HPXe MRI was performed to monitor changes in pulmonary function during disease progression and pharmacological therapy.

Results:

HPXe metrics of fractional ventilation and gas-exchange function were significantly reduced after 6 weeks of CS and LPS exposure compared to sham-instilled mice administered with saline (P < 0.05). After this observation, EP administration was started in 16 of the 32 mice and continued for 4 weeks. EP was found to improve HPXe MRI metrics to a similar level as in sham-instilled mice (P < 0.01). Histological analysis showed significant alveolar tissue destruction in the COPD group, but relatively normal alveolar structure in the EP and sham-instilled groups.

Conclusion:

This study demonstrates the potential efficacy of EP for COPD therapy, as assessed by a noninvasive, translatable 129Xe MRI procedure.

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