Hemoglobin-Based Oxygen Carrier and Altitude Performance in the Rat Model

Abstract

Hemoglobin-based oxygen carriers (HBOC) may enhance oxygen carrying capacity of blood and potentially improve human performance at altitude. Oxygen delivery to exercising muscle may be enhanced with HBOC. PURPOSE: To determine, in the exercising rat model, if HBOC at altitude would increase exercise performance; and to investigate underlying hemodynamic determinants of oxygen delivery. METHODS: Study One: conscious male Sprague-Dawley rats rats were habituated to run on a treadmill for 4 days. On the study day, rats were randomly assigned to receive either a lactated Ringer's solution or an HBOC (Oxyglobin™, Biopure) via tail vein infusion. Rats were placed in a hypobaric chamber and the barometric pressure reduced to the equivalent of 13,500 ft (4,115 m) for a minimum of 20 min before running to exhaustion on the treadmill. Study Two: rats were acutely instrumented under anesthetic for BP, pulmonary artery pressure, and cardiac output (dye dilution). Animals were randomly assigned to a lactated Ringer's or HBOC group and infused via venous catheter. Following baseline measurements, conscious animals were exposed to either normoxia (FIO2 = 21 %) or hypoxia (FIO2 = 10%) for 4 hrs, with measurements at 2 and 4 hrs. RESULTS: Study One: rats running at altitude infused with lactated Ringer's averaged [mean (SEM)] 604 (142) sec vs. 307 (51) sec for HBOC treated (p=0.03, one-sided t-test). Study Two: HBOC animals both during normoxia and hypoxia had elevated arterial and pulmonary artery pressures, reduced cardiac output and decreased oxygen delivery (cardiac output times arterial oxygen content) [all p<0.05]. Cardiac output (ml/kg) was reduced from 224 (26) to 124 (14) at 4 hrs in normoxia, and from 242 (26) to 130 (12) in hypoxia. This corresponded to decreased oxygen delivery (ml O2/min/kg) from 40 (5) to 22 (2.5) in normoxia and from 23 (2.5) to 15.7 (1.6) in hypoxia, at 4 hrs. CONCLUSIONS: These studies suggest that HBOC reduces exercise performance at altitude because of its negative impact on cardiovascular function and oxygen delivery, despite increasing oxygen content. HBOC may alter cardiovascular function as a result of NO scavenging by the plasma borne hemoglobin (HBOC). Supported by the Defense Advanced Research Projects Agency (DARPA) and the Army Research Office (ARO) contract number W911NF-06-1-0318.