Endotoxin-induced shock in the pig--limited effects of low and high concentrations of inhaled nitric oxide.
OBJECTIVE
This study was carried out to study the prophylactic effects of inhalation of nitric oxide (NO) before and during the induction of endotoxic shock.


METHODS
Eighteen anaesthetized pigs received an infusion of 10-20 microg kg(-1) endotoxin during 2 h after pre-treatment with the cortisol-synthesis inhibitor metyrapone. Three groups were tested (n = 6 each) and received 0, 0.2 or 20 ppm inhaled NO from 30 min before start of endotoxin infusion until 4 h after start of endotoxin. Both 0.2 and 20 ppm NO were able to improve blood gas values.


RESULTS
Area above curve values of arterial P2/FiO2 from 0 to 4 h were 0.83 +/- 0.09 kPa h (control), 0.78 +/- 0.22 (0.2 ppm NO, non-significant) and 0.31 +/- 0.06 (20 ppm NO, P < 0.01, Mann-Whitney U-test, compared to control). Area under curve values of PCO2 from 0 to 4 h were 3.96 +/- 0.66 kPa h (control), 1.20 +/- 0.46 (0.2 ppm NO, P < 0.05, Mann-Whitney U-test, compared to control) and 2.78 +/- 1.06 (20 ppm NO group, non-significant). The increase in pulmonary arterial pressure (PAP) was partly prevented by 20 ppm NO, but not by 0.2 ppm NO at 4 h. Inhaled NO did not affect the levels of BAL fluid total protein, tumour necrosis factor-alpha, interleukin-8 and neutrophil counts.


CONCLUSIONS
The addition of a high (20 ppm), but not a low (0.2 ppm), concentration of NO to the inhaled air during endotoxin shock improves arterial oxygen tension and reduces pulmonary artery pressure. Neither dose affects lung mechanics or inflammatory indices, in spite of being given prophylactically.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D019446:Endotoxemia / Q000503:physiopathology; D004731:Endotoxins / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D016209:Interleukin-8 / Q000032:analysis; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000032:analysis / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008797:Metyrapone / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000032:analysis; D011506:Proteins / Q000032:analysis; D051381:Rats; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000963:Antimetabolites; D004731:Endotoxins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008797:Metyrapone