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5‐hydroxymethyl‐2‐furfural (5HMF) Improves Exercise Capacity During Normoxia and Preserves Cardiovascular Function During Severe Hypoxia in Exercising Swine
Author(s) -
Williams Brian T,
Ciarlone Geoffrey E,
Mahon Richard T,
Swift Joshua M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb589
Subject(s) - medicine , hypoxia (environmental) , vo2 max , treadmill , anesthesia , time trial , acclimatization , hemoglobin , room air distribution , oxygen , zoology , heart rate , chemistry , biology , blood pressure , botany , physics , organic chemistry , thermodynamics
BACKGROUND Modern military operations at high altitudes >5,000m result in reduced warfighter performance due to a lack of acclimatization. The exercise performance decrements are attributed to acute exposure to hypobaric hypoxia (HH), characterized by reduced arterial oxygen content and oxygen tissue delivery. The compound 5‐hydroxymethyl‐2‐furfural (5HMF), facilitates oxygen binding to hemoglobin (HgB) at low FiO 2 . Recent swine experiments in our lab demonstrated that 5HMF can increase oxygen‐HgB affinity, reduce cardiopulmonary decrements, and improve survival time during normobaric hypoxia (10% FiO 2 ) exposure. The experiment determined if prophylactic treatment with 5HMF would mitigate hypoxia‐dependent decrements in exercise performance. METHODS Castrated Yorkshire swine (30–35kg, n=9) completed a one week treadmill familiarization protocol, followed by a baseline maximal exercise test (BET) consisting of staged increases in speed at a fixed 19% grade. Animals were randomized to receive IV infusion of either normal saline (VEH) or 5HMF (20mg/kg; 2hrs pre‐testing) and completed two additional maximal exercise tests during exposure to normoxic air (21% FiO 2 ) (NET) and hypoxia (12% FiO 2 ) (HET) on successive days. The same three tests (BET, NET, and HET) were completed the following week with the other IV treatment not used during the first testing week, allowing each animal to serve as its own control. Physiological parameters collected included cardiovascular and exercise performance during baseline, exercise, and recovery phases. RESULTS HET led to ~40% lower total exercise time compared to both normoxic tests [BET (p=0.001) and NET (p=0.001)] regardless of treatment. During NET, 5HMF resulted in a 7% greater peak workload (METS) than BET (p=0.02) that was not seen with VEH (p=0.07). During HET, 5HMF resulted in a similar mean workload as VEH (p=0.6), but reduced peak heart rate by 12% (p=0.04, n=4). Average heart rate during recovery from HET was 6% lower in swine administered 5HMF compared to recovery following NET (p=0.02). CONCLUSIONS This study developed an exercise model in swine exposed to acute hypoxia that reliably reduced exercise performance. Using our model, we observed that 5HMF increased exercise capacity under normoxic conditions and preserved cardiovascular function during and immediately after exercising in severe hypoxic conditions. This work further demonstrates the utility of using an oxygen‐HgB affinity increasing compound (5HMF) to improve operational effectiveness and capabilities in high altitude environments without the need for prior acclimatization. Support or Funding Information Office of Naval Research, USUHS Grant, HU0001‐14‐1‐0008 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .