In an intensive-care setting we studied the effects of ketoprofen, a dual inhibitor of cyclooxygenase and lipoxygenase, on circulatory and respiratory changes during established endotoxic shock in sheep. Two groups (n = 7 in each) were exposed to E. coli endotoxin, which caused a sharp increase in pulmonary artery pressure (200%; PAP), intrapulmonary shunt fraction (300%; QS/QT%), and oxygen extraction ratio (50%; VO2/DO2%). There was also a significant decrease in mean arterial pressure (25%; MAP), respiratory compliance (60%; CT), arterial oxygen tension (65%; PaO2), and oxygen delivery index (15%; DO2) in both groups. After 30 min of endotoxin infusion, group K received ketoprofen, 2.5 mg/kg b.w. i.v., while group E served as shock controls. After 4 h there had been a significant improvement in MAP, PaO2, DO2, QS/QT%, and CT in the ketoprofen-treated group compared with the controls (P < 0.01). In addition, the oxygen extraction ratio normalised in group K, but remained 70-100% increased in group E (P < 0.01). The wet-to-dry weight ratios of the lungs and the liver were significantly lower in the ketoprofen-treated group compared with the controls (P < 0.05). It was concluded that ketoprofen significantly ameliorated the respiratory and circulatory effects of established endotoxic shock in sheep.

Metabolites of arachidonic acid are known to play an important part in the pathogenesis of organ injury in endotoxic shock. We compared the effects of the classical cyclooxygenase inhibitor aspirin with that of the dual cyclooxygenase and lipoxygenase inhibitor ketoprofen on the behavior of platelets tagged with 111In-labeled oxine in multiple organs during endotoxin shock. Three groups of sheep (n = 7 in each) were anesthetized before being subjected to endotoxin shock. Group E had no drug treatment (shock controls), group KET received ketoprofen and group ASP received aspirin treatment. In the lungs and in the liver of group E there was a marked sequestration of platelets, which started in both organs immediately after administration of endotoxin and continued throughout the study. In the treated groups, however, the response to endotoxin was both delayed and reduced compared with the untreated shock controls. The first changes in platelet activity were noted after more than 1 h in the treated groups. Four hours after administration of endotoxin, platelet activity (sequestration) had increased in the lungs by 102 +/- 14% in group E, 53 +/- 11% in group ASP and 20 +/- 13% in group KET (P < 0.01, P < 0.01 and P < 0.05 respectively compared to baseline). Corresponding values for the liver were 52 +/- 16% in group E, 22 +/- 19% in group ASP and -2 +/- 12% in group KET (P < 0.01, P < 0.01 and P > 0.05 respectively compared with baseline).(ABSTRACT TRUNCATED AT 250 WORDS)

In an intensive care setting we studied the effects of pentoxifylline on hemodynamics, gas-exchange and platelet sequestration in multiple organs in three groups of sheep exposed to endotoxin shock (n = 7 in each). Group P-E was given pentoxifylline before and group E-P after E. coli endotoxin infusion, while group E received normal saline (controls). The endotoxin infusion caused a three-fold increase in pulmonary artery pressure (PAP) and a significant decrease in mean arterial pressure (25-30%; MAP), respiratory compliance (CT; 60%) and arterial oxygen tension (65-70%; Pao2) in all groups after 30 min. After 4 h MAP had improved significantly in the pretreated animals (group P-E) and arterial pH, Pao2 and CT improved in both pentoxifylline-treated groups compared with the controls. On the other hand, the effects of endotoxin on PAP and cardiac index were not significantly influenced by pentoxifylline treatment. In addition, there was a pronounced platelet sequestration in the lungs and in the liver in groups E and E-P during the 4 h study, but in the pretreated group (group P-E) the changes were significantly less marked (P < 0.01). The wet-to-dry weight ratios of the lungs were significantly lower in both pentoxifylline-treated groups compared with the controls (P < 0.01). It was concluded that pentoxifylline modified the effects of endotoxin on hemodynamics, gas exchange and platelet sequestration in the lungs and liver in sheep when it was given prior to endotoxin. However, when it was given after hemodynamic and respiratory signs of shock had appeared, the effects were more moderate.

No abstract

Ketoprofen completely prevented the changes in hemodynamics and respiratory function observed in control-endotoxin-treated animals.