Effects of NO inhalation on pulmonary leukocyte sequestration and blood volume in porcine endotoxaemia

Objective: Sequestration and mil:ration of activated neutrophils plays a ma jor role in the pulmonary injury typical of septic shock and the adult resp iratory distress syndrome. Inhaled NO may counteract alveolar-capillary dam age attributed to activated neutrophils. The present study describes a meth od to directly demonstrate the effects of NO inhalation on endotoxin-induce d sequestration of (99)mTc-labelled leukocytes [A(s)(t)] in the lungs of pi gs. Design: Prospective controlled study. Setting: Laboratory for experimental surgery at a university medical centre . Subjects: Anaesthetised and ventilated pigs. Interventions: To induce inflammatory shock 26 animals received a continuou s endotoxin infusion. Thirteen animals inhaled NO from the start of the exp eriments, while 13 served as controls. In 13 animals from both groups, leuk ocytes were labelled in vitro and reinjected, while hi the 13 others erythr ocytes were labelled in vivo to provide corrections for changes in blood vo lume. Measurements and results: The pulmonary distribution of Tc-99m-la-belied le ukocytes or erythrocytes was studied dynamically for 180 min, After correct ion for changes in pulmonary and heart blood volume (PBV, HBV), leukocyte s equestration curves were generated. Endotoxin induced pulmonary vasoconstri ction, reduced PBV, impaired oxygenation, and caused a maximum increase in A(s)(t) of 30 % in the lungs. NO inhalation attenuated pulmonary vasoconstr iction and the reduction in PBV. The maximum increase in A(8)(t) was reduce d to 15 % of baseline. Conclusions: Inhaled NO exerts its main vascular effects in the pulmonary m icrovasculature, the primary site of physiological neutrophil margination a nd pathological adhesion of activated leukocytes. Early use of NO inhalatio n may offer protection against the development of more lasting pulmonary fa ilure in septic shock by reducing leukocyte sequestration in the lungs.