title: Hemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans.
abstract: OBJECTIVE
  The objective of this study was to evaluate the exercise capacity of subjects given an autologous transfusion or a polymerized bovine hemoglobin solution to define the pharmacodynamics and pharmacokinetics of a new hemoglobin-based oxygen carrier (HBOC-201).
  
  
  METHODS
  Six normal healthy male subjects (ages 25 to 45 years) participated in this randomized, single-blind, two-way crossover study, which took place at Upjohn Research Clinics in Kalamazoo, Mich. A radial artery catheter was inserted in each subject before serial cardiac output and pulmonary 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 Ringer's lactate plus an autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine hemoglobin of HBOC-201 (or autologous transfusion). Bicycle exercise stress tests to anaerobic threshold (approximately 65% of predicted maximum aerobic capacity) were done before phlebotomy and at approximately 45 minutes after the autologous transfusion or HBOC-201 infusion.
  
  
  RESULTS
  Subjects had similar exercise and diffusion capacity but lower lactate levels (for up to 24 hours) during HBOC-201 (which paralleled plasma HBOC-201 levels) than during autologous transfusion periods. Oxygen use (uptake) and carbon dioxide production at rest were greater during the HBOC-201 infusion than during the autologous transfusion period. The half-life of HBOC-201 was about 23 hours.
  
  
  CONCLUSIONS
  Exercise capacity and diffusion capacity were similar after HBOC-201 and autologous transfusion. HBOC-201 resulted in greater oxygen (or uptake) and carbon dioxide production and lower lactate levels compared with autologous transfusion. Under the conditions of the study, the physiologic effects of 1 gm bovine hemoglobin of HBOC-201 were similar to 3 gm human hemoglobin from autologous transfusion.
authors.affiliation: Upjohn Company, Kalamazoo, MI 49001, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Hughes
authors.forename: E P
authors.initials: EP
authors.lastname: Yancey
authors.forename: R
authors.initials: R
authors.lastname: Albrecht
authors.forename: P K
authors.initials: PK
authors.lastname: Locker
authors.forename: S F
authors.initials: SF
authors.lastname: Francom
authors.forename: E P
authors.initials: EP
authors.lastname: Orringer
authors.forename: E J
authors.initials: EJ
authors.lastname: Antal
authors.forename: E E
authors.initials: EE
authors.lastname: Jacobs
mesh_terms: D000328:Adult; D001802:Blood Substitutes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004734:Energy Metabolism; D017079:Exercise Tolerance / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects*; D010865:Pilot Projects; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D016037:Single-Blind Method
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201