title: Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: an exploratory study in a swine controlled haemorrhage model.
abstract: BACKGROUND
  Vasoconstriction is a side effect that may prevent the use of haemoglobin based oxygen carrier (HBOC) as blood substitute. Therefore, we tested the hypothesis that the NO donor, sodium nitroprusside (SNP), would mitigate systemic and pulmonary hypertension associated with HBOC-201 in a simple controlled haemorrhage swine model.
  
  
  METHODS
  After 55% estimated blood volume withdrawal through a venous catheter, invasively anesthetized and instrumented animals were resuscitated with three 10 ml/kg infusions of either HBOC-201 or Hextend (HEX) with or without 0.8 μg/kg/min SNP (infused concomitantly via different lines). Haemodynamics, direct and indirect measures of tissue oxygenation, and coagulation were measured for 2h.
  
  
  RESULTS
  Haemorrhage caused a state of shock manifested by hypotension and base deficit. HBOC-201 resuscitation resulted in higher systemic (p<0.0001) and pulmonary (p<0.002) blood pressure than with HEX. Elevation of systemic (p<0.0001) but not pulmonary (p>0.05) arterial pressure was attenuated by co-infusion of SNP, without significant group differences in haemodynamics, tissue oxygenation, platelet function, coagulation, methaemoglobin, or survival (p>0.05).
  
  
  CONCLUSIONS
  In swine with haemorrhagic shock, co-administration of the NO donor, SNP, effectively and safely reduces HBOC-201-related systemic but not pulmonary vasoactivity. Interestingly, co-administration of the vasodilator SNP with HEX had no deleterious effects in comparison with HEX alone.
authors.affiliation: Naval Medical Research Center, NeuroTrauma Department, Silver Spring, MD 20910-7500, United States. Francoise.arnaud@med.navy.mil
authors.forename: Françoise
authors.initials: F
authors.lastname: Arnaud
authors.forename: Anke H
authors.initials: AH
authors.lastname: Scultetus
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.forename: Biswajit
authors.initials: B
authors.lastname: Saha
authors.forename: Bobby
authors.initials: B
authors.lastname: Kim
authors.forename: Charles
authors.initials: C
authors.lastname: Auker
authors.forename: Paula
authors.initials: P
authors.lastname: Moon-Massat
authors.forename: Richard
authors.initials: R
authors.lastname: McCarron
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
mesh_terms: D000818:Animals; D001802:Blood Substitutes; D004195:Disease Models, Animal; D006439:Hemodynamics; D006454:Hemoglobins / Q000494:pharmacology* / Q000627:therapeutic use; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension; D006976:Hypertension, Pulmonary; D009599:Nitroprusside / Q000494:pharmacology* / Q000627:therapeutic use; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D009599:Nitroprusside; C096798:HBOC 201