Prevention of hemodilution-induced inhibition of hypoxic pulmonary vasoconstriction by N-acetylcysteine in dogs.
We investigated the possible contributions of reactive oxygen species and of viscosity changes to hemodilution-induced inhibition of hypoxic pulmonary vasoconstriction (HPV) in dogs. Fourteen isoflurane-anesthetized dogs were randomly assigned to receive N-acetylcysteine (NAC) 200 mg/kg IV (n = 7) or placebo (n = 7). Mean pulmonary artery pressure (Ppa) was measured with cardiac output maintained constant by a manipulation of venous return in hyperoxia (fraction of inspired oxygen, 0.4) and in hypoxia (fraction of inspired oxygen, 0.1) at baseline and after stepwise reductions in hematocrit from 40% to 20%. Measured Ppa was compared with predicted Ppa by using a viscoelastic model. HPV was expressed as hypoxic Ppa minus hyperoxic Ppa. Hemodilution was associated with a decrease in HPV from 7 +/- 1 mm Hg to 3 +/- 1 mm Hg (P < 0.01), and this was completely prevented by NAC (HPV was unchanged, from 8 +/- 1 to 8 +/- 1 mm Hg; not significant). Hemodilution in the model decreased HPV from 8 +/- 1 mm Hg to 6 +/- 1 mm Hg (P < 0.05). We conclude that hemodilution-induced inhibition of HPV is in part explained by viscosity changes and can be prevented by the administration of NAC, which is possibly explained by the scavenging of reactive oxygen species.
Department of Anesthesia and Intensive Care, Timone Hospital, Marseille, France.
François
F
Kerbaul
Philippe
P
Van der Linden
Sébastien
S
Pierre
Benoît
B
Rondelet
Christian
C
Melot
Serge
S
Brimioulle
Robert
R
Naeije
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006438:Hemodilution / Q000009:adverse effects*; D000860:Hypoxia / Q000503:physiopathology; D008170:Lung Compliance / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D000111:Acetylcysteine