Leukotriene receptor antagonism prevents lung protein leakage and hypoxaemia in a septic cat model.
Products of the arachidonic acid cascade have been found to play an important role in the pathophysiology in experimental shock and in ARDS. The effect of cysteinyl-leukotriene (cLT) blockade on the development of respiratory failure during septic shock was examined. Ventilated cats received an infusion of Escherichia coli bacteria. Pretreatment was given with diethylcarbamazine (DEC), a leukotriene synthetase inhibitor, or a new potent cLT receptor antagonist, ICI 198,615. With a gamma camera, the distributions of plasmatransferrin radiolabelled with indium-113m chloride (113mIn) and erythrocytes radiolabelled with technetium-99m (99mTc) were measured over the lungs. A normalized slope index (NSI) reflecting protein leakage, based on the transferrin extravasation, was calculated. In the nonseptic control group (n = 7) NSI was 4.4 x 10(-4) +/- 0.7 x 10(-4).min-1 (mean +/- SEM). Unpretreated septic animals (n = 7) showed a protein leakage after bacterial infusion, with a NSI of 34 +/- 3.5 x 10(-4).min-1. Pretreatment with DEC (n = 6) significantly reduced NSI to 16 +/- 1.5 x 10(-4).min-1. In the group pretreated with ICI 198,615 (n = 8), NSI was 9 +/- 1.2 x 10(-4).min-1. Arterial oxygen tension (PaO2) remained at baseline level of 20 +/- 1.0 kPa during the experimental period in both the nonseptic control group and the ICI 198,615 pretreated group. In the unpretreated septic group, PaO2 fell progressively from a preseptic value of 21 +/- 0.9 to 12 +/- 1.5 kPa after 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Schützer
K M
KM
Dept of Pulmonary Medicine, Renströmska Hospital, University of Göteborg, Sweden.
Larsson
A
A
Risberg
B
B
Falk
A
A
D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002415:Cats; D004049:Diethylcarbamazine / Q000494:pharmacology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000209:etiology / Q000517:prevention & control*; D007191:Indazoles / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood / Q000473:pathology / Q000503:physiopathology*
D007191:Indazoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; C054217:ICI 198615; D004049:Diethylcarbamazine