HEMOGLOBIN-BASED OXYGEN CARRIER PRESERVES SUBMAXIMAL EXERCISE CAPACITY IN HUMANS

Objective: The objective of this study was to evaluate the exercise ca pacity of subjects given an autologous transfusion or a polymerized bo vine hemoglobin solution to define the pharmacodynamics and pharmacoki netics of a new hemoglobin-based oxygen carrier (HBOC-201). Methods: S ix normal healthy male subjects (ages 25 to 45 years) participated in this randomized, single-blind, two-way crossover study, which took pla ce at Upjohn Research Clinics in Kalamazoo, Mich. A radial artery cath eter was inserted in each subject before serial cardiac output and pul monary function tests and phlebotomy of 15% blood volume (750 ml plus another 250 ml for study laboratories yields 1000 ml, or about 150 gm human hemoglobin), This was followed by isovolemic hemodilution with R inger's lactate plus an autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine hemoglobin of HBOC-201 (or autologous trans fusion). Bicycle exercise stress tests to anaerobic threshold (approxi mate to 65% of predicted maximum aerobic capacity) were done before ph lebotomy and at approximate to 45 minutes after the autologous transfu sion or HBOC-201 infusion. Results: Subjects had similar exercise and diffusion capacity but lower lactate levels (for up to 24 hours) durin g HBOC-201 (which paralleled plasma HBOC-201 levels) than during autol ogous transfusion periods. Oxygen use (uptake) and carbon dioxide prod uction at rest were greater during the HBOC-201 infusion than during t he autologous transfusion period. The half-life of HBOC-201 was about 23 hours. Conclusions: Exercise capacity and diffusion capacity were s imilar after HBOC-201 and autologous transfusion. HBOC-201 resulted in greater oxygen (or uptake) and carbon dioxide production and lower la ctate levels compared with autologous transfusion. Under the condition s of the study the physiologic effects of 1 gm bovine hemoglobin of HB OC-201 were similar to 3 gm human hemoglobin from autologous transfusi on.