Increased Hemoglobin Oxygen Affinity With 5-Hydroxymethylfurfural Supports Cardiac Function During Severe Hypoxia

• Published in: Frontiers in physiology 2019-10, Vol.10, p.1350-1350
• Main Authors: Lucas, Alfredo, Ao-ieong, Eilleen S. Y., Williams, Alexander T., Jani, Vivek P., Muller, Cynthia R., Yalcin, Ozlem, Cabrales, Pedro
• Format: Article
• Language: English
• Subjects: 5-HMF; allosteric effectors; cardiac function; conductance catheter; hemoglobin; oxygen delivery; Physiology
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2019.01350

Acclimatization to hypoxia or high altitude involves physiological adaptation processes, to influence oxygen (O 2 ) transport and utilization. Several natural products, including aromatic aldehydes and isothiocyanates stabilize the R-state of hemoglobin (Hb), increasing Hb-O 2 affinity and Hb-O 2 saturation. These products are a counter intuitive therapeutic strategy to increase O 2 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-O 2 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% O 2 , 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-O 2 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 O 2 delivery during hypoxic hypoxia.