Therapeutic effects of inhaled carbon monoxide on endotoxic shock-induced lung injury in pig

Purpose: pre-treatment with inhaled carbon monoxide (CO, 250 ppm in air) one our before LPS infusion prevented respiratory derangements and ameliorated hyperacute endotoxic shock in pigs. In this study we have tested the efficacy of CO administration at peak effect of LPS-induced lung injury in a well established model of endotoxic shock in pigs. Methods: Eight SPF Large White pigs, weighing 23.0 ± 2.54 kg (Mean ± d.s.), sedated and anaesthetised, were tracheostomised and mechanically ventilated. The animals of group 1 (n=4) were treated with LPS of E. coli (40mg/kg/h i.v. for 240 minutes), while those of group 2 (n=4) received LPS, as group 1 and, at 30’ of lipopolisaccaride infusion, inhaled CO for 60 minutes (250 ppm in air). In all animal we have monitored the respiratory flow, tidal volume and tracheal pressure, while the compliance and the resistance of the respiratory system were calculated using standard formulas. We have also monitored systemic and pulmonary arterial pressure and cardiac output. Extravascular lung water volumes (EVLW) were evaluated using a thermodilution technique. At the end of the experimental procedure, lung tissue sample were collected for wet/dry analysis. All signals were recorded every 30 minutes on a multichannel pen recorder polygraph and blood samples were collected for blood gas, hematocrit, biochemical and coagulative analysis. Results: In the CO-treated pigs, the percent carboxyhemoglobin rose to 13.08 ± 0.55 after 1 hour of CO inhalation and returned to baseline (4.28 ± 0.18%) 90’ after discontinuing CO and starting 100% O2 inhalation. CO treatment completely prevented the LPS induced decrease in respiratory compliance and the increase in EVLW, as reflection of lesser edema formation. This observation was confirmed by wet /dry lung tissue ratio that was lower in the CO group and by hematocrit levels that, from 180’ of LPS infusion, were lower in the CO treated group. Moreover, CO treatment ameliorated the degree of acidosis ensued during the LPS infusion. Our study shows that CO treatment improved heart function, preventing the progressive and continuing decreases in stroke volume (SV) induced by LPS. Finally, CO treatment improved the coagulation status, reflected by a significant reduction in D-dimer formation. Conclusion: This is one of the first studies on a large animal model showing that CO, administered after the disease-inducing stimulus, exerts beneficial effects. Acknowledgments: This work was supported by a grant from the Italian Ministero dell’Istruzione dell’Università e della Ricerca (COFIN 2003).