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Cited by 113Erythropoietin and Anemia TreatmentCardiovascular and exercise physiologyHigh Altitude and Hypoxia

Optimal hematocrit for maximal exercise performance in acute and chronic erythropoietin-treated mice

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Schuler, Beat, Arras, Margarete, Keller, Stephan, Rettich, Andreas, Lundby, Carsten, Vogel, Johannes, Gassmann, Max·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0912924107PMC PMC2806754
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Abstract

Erythropoietin (Epo) treatment increases hematocrit (Htc) and, consequently, arterial O 2 content. This in turn improves exercise performance. However, because elevated blood viscosity associated with increasing Htc levels may limit cardiac performance, it was suggested that the highest attainable Htc may not necessarily be associated with the highest attainable exercise capacity. To test the proposed hypothesis that an optimal Htc in acute and chronic Epo-treated mice exists—i.e., the Htc that facilitates the greatest O 2 flux during maximal exercise—Htc levels of wild-type mice were acutely elevated by administering novel erythropoiesis-stimulating protein (NESP; wtNESP). Furthermore, in the transgenic mouse line tg6 that reaches Htc levels of up to 0.9 because of constitutive overexpression of human Epo, the Htc was gradually reduced by application of the hemolysis-inducing compound phenylhydrazine (PHZ; tg6PHZ). Maximal cardiovascular performance was measured by using telemetry in all exercising mice. Highest maximal O 2 uptake and maximal time to exhaustion at submaximal exercise intensities were reached at Htc values of 0.58 and 0.57 for wtNESP, and 0.68 and 0.66 for tg6PHZ, respectively. Rate pressure product, and thus also maximal working capacity of the heart, increased with elevated Htc values. Blood viscosity correlated with Apart from the confirmation of the Htc hypothesis, we conclude that tg6PHZ adapted better to varying Htc values than wtNESP because of the higher optimal Htc of tg6PHZ compared to wtNESP. Of note, blood viscosity plays a critical role in limiting exercise capacity.

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Authors
Schuler, B., Arras, M., Keller, S., Rettich, A., Lundby, C., Vogel, J., & Gassmann, M.
Affiliations
University of Zurich (CH)
Corresponding author
Gassmann, Max
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-12-29
Volume
107
Issue
1
Pages
419-423
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0912924107
PMC
PMC2806754
OpenAlex
W2083822375
Cited by
113
References
35
Citations by year
2026: 1 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 10 · 2018: 12 · 2017: 3 · 2016: 15 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 8
FWCI
4.65
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Topics
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
Keywords
hematocrit, erythropoietin, exercise performance, blood viscosity, oxygen consumption, time to exhaustion, phenylhydrazine, erythropoiesis-stimulating proteins, transgenic mice, cardiovascular performance, rate-pressure product, hemolysis
MeSH terms
Animals, Blood Pressure, Blood Viscosity, Blood Volume, Erythropoietin, Exercise Test, Heart Rate, Hematocrit, Humans, Male, Mice, Transgenic, Myocardium, Oxygen Consumption, Physical Endurance, Exercise, Exercise Tolerance, Mice

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