Cardiovascular Parameters in a Swine Model of Normobaric Hypoxia Treated With 5-Hydroxymethyl-2-Furfural (5-HMF)

INTRODUCTION: The consequences of low partial pressure of O(2) include low arterial O(2) saturations (SaO(2)), low blood O(2) content (CaO(2)), elevated mean pulmonary artery pressure (PAP), and decreased O(2) consumption VO(2). 5-hydroxymethyl-2-furfural (5-HMF) binds to the N-terminal valine of hemoglobin (HgB) and increases its affinity to O(2). We used an instrumented, sedated swine model to study the effect of 5-HMF on cardiovascular parameters during exposure to acute normobaric hypoxia (NH). METHODS: Twenty-three sedated and instrumented swine were randomly assigned to one of three treatment groups and received equal volume of normal saline (VEH), 20 mg/kg 5-HMF (5-HMF-20) or 40 mg/kg 5-HMF (5-HMF-40). Animals then breathed 10% FiO(2) for 120 min. Parameters recorded were Cardiac Output (CO), Mean Arterial Blood Pressure (MAP), Heart Rate (HR), Mean Pulmonary Artery Pressure (PAP), SaO(2) and saturation of mixed venous blood (SvO(2)). The P(50) was measured at fixed time intervals prior to and during NH. RESULTS: 5-HMF decreased P(50). In the first 30 min of NH, treatment with 5-HMF-20 and 5-HMF-40 resulted in a (1) significantly smaller decrement in SaO(2) and SvO(2), (2) significantly lower HR and CO, and (3) smaller increase in PAP compared to VEH. In the 120 min of NH there was a trend toward improved mortality with 5-HMF treatment. CONCLUSION: 5-HMF treatment decreased P(50), improved SaO(2), and mitigated increases in PAP in this swine model of NH.