Prophylactic treatment with an aerosolized corticosteroid liposome in a porcine model of early ARDS induced by endotoxaemia.
The effects of prophylactic treatment with an aerosolized corticosteroid liposome (CSL) in high dose were evaluated in a porcine model of early Adult Respiratory Distress Syndrome (ARDS) induced by endotoxaemia. Intermittent positive pressure ventilated (IPPV) pigs under chlormethiazole anaesthesia were infused with E. coli endotoxin (18 micrograms.kg-1.h-1) over 4 h. Eight animals served as controls and were pretreated with aerosolized placebo liposomes, either 15 min or 2 h, before start of the endotoxin infusion. Eight animals were pretreated with CSL in aerosolized form 15 min before start of endotoxin, and eight animals were pretreated 2 h before start of endotoxin. Pretreatment with CSL, both 15 min and 2 h before endotoxin, modified and partly counteracted the late endotoxin-induced impairment in expiratory resistance (EXPres), dynamic compliance (Cdyn) and mean pulmonary artery pressure (MPAP). The administration of CSL did not seem to have a restrictive influence on the endogenous cortisol production estimated by repeated measurements of serum cortisol levels. These results indicate that CSL, administered prophylactically in an aerosolized form to the lung, might be valuable as a modulator without systemic side effects in regard to some of the endotoxin-induced pulmonary impairments seen in this experimental model of early ARDS.
Department of Anaesthesiology, University Hospital, Uppsala, Sweden.
P E
PE
Forsgren
J A
JA
Modig
C M
CM
Dahlbäck
B I
BI
Axelsson
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D000336:Aerosols; D000818:Animals; D004337:Drug Carriers; D004731:Endotoxins / Q000633:toxicity; D004927:Escherichia coli Infections / Q000209:etiology; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D008081:Liposomes; D008297:Male; D011292:Premedication; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D000336:Aerosols; D004337:Drug Carriers; D004731:Endotoxins; D008081:Liposomes; D006854:Hydrocortisone