title: Prevention of the pulmonary vasoconstrictor effects of HBOC-201 in awake lambs by continuously breathing nitric oxide.
abstract: BACKGROUND
  Hemoglobin-based oxygen-carrying solutions (HBOC) provide emergency alternatives to blood transfusion to carry oxygen to tissues without the risks of disease transmission or transfusion reaction. Two primary concerns hampering the clinical acceptance of acellular HBOC are the occurrence of systemic and pulmonary vasoconstriction and the maintenance of the heme-iron in the reduced state (Fe2+). We recently demonstrated that pretreatment with inhaled nitric oxide prevents the systemic hypertension induced by HBOC-201 (polymerized bovine hemoglobin) infusion in awake mice and sheep without causing methemoglobinemia. However, the impact of HBOC-201 infusion with or without inhaled nitric oxide on pulmonary vascular tone has not yet been examined.
  
  
  METHODS
  The pulmonary and systemic hemodynamic effects of breathing nitric oxide both before and after the administration of HBOC-201 were determined in healthy, awake lambs.
  
  
  RESULTS
  Intravenous administration of HBOC-201 (12 ml/kg) induced prolonged systemic and pulmonary vasoconstriction. Pretreatment with inhaled nitric oxide (80 parts per million [ppm] for 1 h) prevented the HBOC-201--induced increase in mean arterial pressure but not the increase of pulmonary arterial pressure, systemic vascular resistance, or pulmonary vascular resistance. Pretreatment with inhaled nitric oxide (80 ppm for 1 h) followed by breathing a lower concentration of nitric oxide (5 ppm) during and after HBOC-201 infusion prevented systemic and pulmonary vasoconstriction without increasing methemoglobin levels.
  
  
  CONCLUSIONS
  These findings demonstrate that pretreatment with inhaled nitric oxide followed by breathing a lower concentration of the gas during and after administration of HBOC-201 may enable administration of an acellular hemoglobin substitute without vasoconstriction while preserving its oxygen-carrying capacity.
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia and Critical Care, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Binglan
authors.initials: B
authors.lastname: Yu
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Volpato
authors.forename: Keqin
authors.initials: K
authors.lastname: Chang
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Warren M
authors.initials: WM
authors.lastname: Zapol
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006454:Hemoglobins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000008:administration & dosage*; D012119:Respiration / Q000187:drug effects*; D034561:Sheep, Domestic; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000008:administration & dosage; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D006454:Hemoglobins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C096798:HBOC 201; D009569:Nitric Oxide