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Normobaric hypoxia elevates free fatty acids and impairs cardiac energetics and diastolic function in normal human volunteers

Introduction

In the first few days of hypoxic exposure, left ventricular dysfunction is consistently observed in human heart, yet the cellular mechanisms underlying the dysfunction are poorly understood.

Purpose

Our hypothesis was that normobaric hypoxia impairs cardiac energetics, leading to cardiac dysfunction.

Methods

Healthy males from the University of Oxford (n = 12, age 24 ± 2) underwent twenty hours of normobaric hypoxia in purpose-built hypoxia chambers. The partial pressure of oxygen during end tidal expiration (PETO2) was kept between 50 and 60 mmHg, whilst keeping peripheral oxygen saturation (SaO2) above 80%. Cardiac function was measured using magnetic resonance imaging (MRI) and echocardiography. High-energy phosphate metabolism was measured as the ratio of phosphocreatine to ATP (PCr/ATP) by 31Phosphorus magnetic resonance spectroscopy (MRS) before and after twenty hours of hypoxia. Additionally, four subjects had blood taken for biochemical analysis every four hours.

Results

During hypoxia, PETO2 and SaO2 averaged 55 ± 1 mmHg and 83.6 ± 0.4%, respectively. There was a 15% reduction in cardiac PCr/ATP, from 2.0 ± 0.1 to 1.7 ± 0.1 after hypoxia (p < 0.01, Figure 1), reduced diastolic function, measured as E/E', from 6.1 ± 0.4 to 7.5 ± 0.7, (p < 0.01) and a three-fold elevation in plasma Free Fatty Acids (FFAs, p < 0.05).

Figure 1
figure1

Figure 1

Conclusion

Short term normobaric hypoxia led to rapid changes in FFAs, cardiac metabolism and alterations in diastolic function in normal human hearts. Elevated FFAs may lead to impaired high energy phosphate metabolism and cardiac dysfunction after hypoxic exposure.

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Correspondence to Cameron J Holloway.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Holloway, C.J., Cochlin, L.E., Codreanu, I. et al. Normobaric hypoxia elevates free fatty acids and impairs cardiac energetics and diastolic function in normal human volunteers. J Cardiovasc Magn Reson 12, O18 (2010). https://doi.org/10.1186/1532-429X-12-S1-O18

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Keywords

  • Free Fatty Acid
  • Diastolic Function
  • Cardiac Dysfunction
  • Hypoxic Exposure
  • Plasma Free Fatty Acid