Effects of a XXXX synthase inhibitor in @entity1 with @entity326 .

@entity1 @entity295 @entity326 @entity1009 @entity7293 @entity842 @entity432 @entity551
OBJECTIVE: Studies in animals have indicated that increased production of @entity842 from an inducible isoform of @entity842 synthase contributes to the pathophysiology of endotoxic and cytokine induced shock. The aim of this study was to determine the role of @entity842 in @entity326 in @entity1 . METHODS: The study was a randomised, double blind, placebo controlled investigation of the effects of the @entity842 synthase inhibitor @entity7293 ( @entity7293 ) in 12 @entity1 with severe @entity295 associated with @entity551 . Measurements of haemodynamic, haematological, and biochemical variables were made. RESULTS: @entity7293 (0.3 and 1 mg.kg-1) produced a dose dependent increase in mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and @entity432 , and a decrease in cardiac output and heart rate. In response to the highest dose of @entity7293 systemic vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac output decreased from 11.2(2.1) to 8.9(1.9) litres. @entity1009 . Continuous infusion of @entity7293 (1 mg.kg-1 x h-1) produced sustained haemodynamic changes. Platelet numbers decreased during the course of the study in both the @entity7293 and the placebo group and did not differ significantly between the groups. CONCLUSIONS: Low doses of @entity7293 cause a widespread increase in vascular tone and raise blood pressure in @entity1 with @entity326 . Overproduction of @entity842 appears to be an important mechanism in @entity326 in @entity1 , and inhibition of @entity842 synthesis might provide a novel therapeutic approach to this condition. However, @entity7293 produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of @entity7293 on mortality and morbidity are now required.
