Effects of NO inhalation on pulmonary leukocyte sequestration and blood volume in porcine endotoxaemia.
OBJECTIVE
Sequestration and migration of activated neutrophils plays a major role in the pulmonary injury typical of septic shock and the adult respiratory distress syndrome. Inhaled NO may counteract alveolar-capillary damage attributed to activated neutrophils. The present study describes a method to directly demonstrate the effects of NO inhalation on endotoxin-induced sequestration of 99mTc-labelled leukocytes [As(t)] in the lungs of pigs.


METHODS
Prospective controlled study.


METHODS
Laboratory for experimental surgery at a university medical centre.


METHODS
Anaesthetised and ventilated pigs.


METHODS
To induce inflammatory shock 26 animals received a continuous endotoxin infusion. Thirteen animals inhaled NO from the start of the experiments, while 13 served as controls. In 13 animals from both groups, leukocytes were labelled in vitro and reinjected, while in the 13 others erythrocytes were labelled in vivo to provide corrections for changes in blood volume.


RESULTS
The pulmonary distribution of 99mTc-labelled leukocytes or erythrocytes was studied dynamically for 180 min. After correction for changes in pulmonary and heart blood volume (PBV, HBV), leukocyte sequestration curves were generated. Endotoxin induced pulmonary vasoconstriction, reduced PBV, impaired oxygenation, and caused a maximum increase in As(t) of 30% in the lungs. NO inhalation attenuated pulmonary vasoconstriction and the reduction in PBV. The maximum increase in As(t) was reduced to 15% of baseline.


CONCLUSIONS
Inhaled NO exerts its main vascular effects in the pulmonary microvasculature, the primary site of physiological neutrophil margination and pathological adhesion of activated leukocytes. Early use of NO inhalation may offer protection against the development of more lasting pulmonary failure in septic shock by reducing leukocyte sequestration in the lungs.
Dahm
P L
PL
Department of Anaesthesiology, Medical Faculty, University Hospital of Lund, Sweden. peter.dahm@anest.lu.se
Blomquist
S
S
De Robertis
E
E
Jonson
B
B
Myhre
E
E
Svantesson
C
C
Thörne
J
J
D000280:Administration, Inhalation; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology*; D005260:Female; D007962:Leukocytes / Q000187:drug effects*; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D011877:Radionuclide Imaging; D012128:Respiratory Distress Syndrome / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology*; D013552:Swine; D013667:Technetium
D009569:Nitric Oxide; D013667:Technetium