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Increased Hemoglobin Oxygen Affinity With 5-Hydroxymethylfurfural Supports Cardiac Function During Severe Hypoxia
- Source :
- Frontiers in Physiology, Vol 10 (2019), Frontiers in physiology, vol 10, iss OCT, Frontiers in Physiology
- Publication Year :
- 2019
- Publisher :
- Frontiers Media S.A., 2019.
-
Abstract
- Acclimatization to hypoxia or high altitude involves physiological adaptation processes, to influence oxygen (O2) transport and utilization. Several natural products, including aromatic aldehydes and isothiocyanates stabilize the R-state of hemoglobin (Hb), increasing Hb-O2 affinity and Hb-O2 saturation. These products are a counter intuitive therapeutic strategy to increase O2 delivery during hypoxia. 5-Hydroxymethylfurfural (5-HMF) is well known Amadori compound formed during the Maillard reaction (the non-enzymatic browning and caramelization of carbohydrate-containing foods after thermal treatment), with well documented effects in Hb-O2 affinity. This study explores the therapeutic potential of 5-HMF on left ventricular (LV) cardiac function (LVCF) during hypoxia. Anesthetized Golden Syrian hamsters received 5-HMF i.v., at 100 mg/kg and were subjected to stepwise increased hypoxia (15, 10, and 5%) every 30 min. LVCF was assessed using a closed chest method with a miniaturized conductance catheter via continuous LV pressure-volume (PV) measurements. Heart hypoxic areas were studied using pimonidazole staining. 5-HMF improved cardiac indices, including stroke volume (SV), cardiac output (CO), ejection fraction (EF), and stroke work (SW) compared to the vehicle group. At 5% O2, SV, CO, EF, and SW were increased by 53, 42, 33, and 51% with 5-HMF relative to vehicle. Heart chronotropic activity was not statistically changed, suggesting that differences in LV-CF during hypoxia by 5-HMF were driven by volume dependent effects. Analysis of coronary blood flow and cardiac muscle metabolism suggest no direct pharmacological effects from 5-HMF, therefore these results can be attributed to 5-HMF-dependent increase in Hb-O2 affinity. These studies establish that naturally occurring aromatic aldehydes, such as 5-HMF, produce modification of hemoglobin oxygen affinity with promising therapeutic potential to increase O2 delivery during hypoxic hypoxia.<br />National Institutes of Health (NIH); Heart Lung and Blood Institute (HLBI)
- Subjects :
- Cardiac function curve
Cardiac output
Hypoxic hypoxia
left ventricle
Physiology
Medical Physiology
030204 cardiovascular system & hematology
Pharmacology
Cardiovascular
5-HMF
lcsh:Physiology
03 medical and health sciences
0302 clinical medicine
Physiology (medical)
oxygen delivery
medicine
Psychology
conductance catheter
Lung
Allosteric effectors
Cardiac function
Conductance catheter
Hemoglobin
Left ventricle
Oxygen delivery
030304 developmental biology
Original Research
0303 health sciences
Ejection fraction
lcsh:QP1-981
Chemistry
Cardiac muscle
Stroke volume
Hematology
hemoglobin
medicine.anatomical_structure
Heart Disease
Increased hemoglobin oxygen affinity
cardiac function
allosteric effectors
Subjects
Details
- Language :
- English
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Physiology
- Accession number :
- edsair.doi.dedup.....4e913bc07a3558ff14d72ba48cdf1a2c