title: Prolonged exposure to inhaled nitric oxide does not affect haemostasis in piglets.
abstract: OBJECTIVE
  To examine possible adverse effects on haemostasis from prolonged exposure to inhaled nitric oxide (iNO).
  
  
  METHODS
  Blinded, randomised, experimental animal study in a university animal laboratory.
  
  
  METHODS
  Anaesthetised and intubated piglets received central venous, arterial, and transabdominal urinary catheters. Twelve piglets were studied with triggered pressure support ventilation breathing with an air-oxygen mixture for 30 h with nitric oxide (NO), 40 parts per million (ppm) (n = 6) or without NO gas (n = 6) added. The tests of platelet function were assessed in a separate 1-h experiment in which 12 additional animals were blindly randomised to receive intravenous acetylsalicylic acid (ASA) (n = 7) or placebo (n = 5).
  
  
  RESULTS
  All 12 animals were clinically stable during the study period of 30 h. Haemostasis was assessed in terms of bleeding time and platelet function by Adeplat-S, reflecting platelet adhesion. Prothrombin fragment 1 + 2, fibrin D-dimer, tissue plasminogen activator and prothrombin complex were measured to investigate whether inhaled NO (iNO) had any effects on thrombin formation, fibrin formation, fibrinolysis or coagulation. All parameters including bleeding time and Adeplat-S were unaffected by iNO. ASA significantly increased bleeding time, but did not affect Adeplat-S. Nitrate in plasma and NOx (nitrate and nitrite) in urine increased significantly in pigs receiving iNO compared with controls.
  
  
  CONCLUSIONS
  Prolonged exposure to iNO at 40[Symbol: see text]ppm did not affect bleeding time or coagulation parameters in healthy piglets. The findings do not support the hypothesis that iNO increases the risk of bleeding in humans.
authors.affiliation: Danderyd University Hospital, Karolinska Institutet, Department of Clinical Sciences, Division of Anaesthesia and Intensive Care, SE-18288 Stockholm, Sweden. Johanna.Albert@ds.se
authors.forename: Johanna
authors.initials: J
authors.lastname: Albert
authors.forename: Piotr
authors.initials: P
authors.lastname: Harbut
authors.forename: Stanisław
authors.initials: S
authors.lastname: Zieliński
authors.forename: Stanisław
authors.initials: S
authors.lastname: Ryniak
authors.forename: Caroline
authors.initials: C
authors.lastname: Gillis-Haegerstrand
authors.forename: Robert
authors.initials: R
authors.lastname: Lindwall
authors.forename: Leszek
authors.initials: L
authors.lastname: Solski
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.forename: Jan
authors.initials: J
authors.lastname: Svensson
authors.forename: Waldemar
authors.initials: W
authors.lastname: Goździk
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D001760:Bleeding Time; D001779:Blood Coagulation Factors / Q000032:analysis / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects; D006487:Hemostasis; D007958:Leukocyte Count; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000008:administration & dosage*; D009573:Nitrites / Q000097:blood / Q000652:urine; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011498:Protein Precursors / Q000097:blood / Q000187:drug effects; D011516:Prothrombin / Q000187:drug effects; D011897:Random Allocation; D013552:Swine
chemical_list: D001779:Blood Coagulation Factors; D001993:Bronchodilator Agents; D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011498:Protein Precursors; C036309:fibrin fragment D; D009569:Nitric Oxide; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D002097:C-Reactive Protein; D001241:Aspirin