Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Lack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Losartan is a potent pharmaceutical drug for ALI/ARDS. However, the protective effects and mechanisms of losartan remain incompletely known. ⋯ Finally, losartan given after sepsis led to inhibition of lung tissue NF-kappaB activation (P < 0.01 vs. CLP group), attenuated degradation of IkappaB-alpha, and inhibited phosphorylation of p38MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, pathways critical for cytokine release. These data reveal that losartan exerts a protective effect on ALI/ARDS, and this protective effect may be dependent, at least in part, on NF-kappaB and MAPK mechanisms.
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We aimed to determine retrospectively whether urinary liver-type fatty acid-binding protein (L-FABP) levels are altered in patients with septic shock or severe sepsis without shock and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects these levels. Forty patients with septic shock, 20 patients with severe sepsis without shock, 20 acute renal failure (ARF) patients without septic shock (mean serum creatinine, 2.8 mg/dL), and 30 healthy volunteers were included in this study. Polymyxin B-immobilized fiber hemoperfusion was performed twice in 40 patients. ⋯ Polymyxin B-immobilized fiber treatment reduced plasma endotoxin levels (P < 0.01) and urinary L-FABP levels (P < 0.01). In 10 patients with septic shock without PMX-F treatment, L-FABP levels remained high 7 days after initiation of conventional treatment (P = 0.12). These results suggest that urinary L-FABP levels are significantly increased in patients with septic shock and that PMX-F treatment is effective in reducing these levels.
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Excess production of NO and activation of vascular ATP-sensitive potassium (K(ATP)) channels are implicated in the hypotension and vascular hyporeactivity associated with endotoxic shock. Using a fluid-resuscitated endotoxic rat model, we compared the cardiovascular effects of an iNOS inhibitor and two distinct inhibitors of the K(ATP) channel. Endotoxin (LPS) was administered to anesthetized, spontaneously breathing, fluid-resuscitated adult male Wistar rats, in which MAP, aortic and renal blood flow, and hepatic microvascular oxygenation were monitored continuously. ⋯ We conclude that inhibition of the K(ATP) channel via the pore-forming, but not the sulfonylurea receptor subunit, increases blood pressure in a short-term endotoxic model. However, this was not accompanied by any improvement in macrocirculatory or microcirculatory organ blood flow nor reversal of metabolic acidosis. It therefore remains uncertain whether the iNOS pathway or the K(ATP) channel represents a potential target for drug development in the treatment of endotoxic shock.