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
-
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.
-
Most multiple organ failure (MOF) scores were developed over a decade ago, but little has been done in terms of validation and to understand the differences between populations identified by each of them. Given the lack of a gold standard, validation must rely on association with objective adverse outcomes. Thus, we propose to (a) validate two widely accepted MOF scores (Denver and Marshall), examining their association with adverse outcomes in a postinjury population; and (b) compare risk factors, characteristics, and outcomes of patients identified by each score. ⋯ Values of sensitivity and specificity were more than 70% for death and ventilator-free days (with the Denver score showing a consistent trend toward greater specificity), but either sensitivity or specificity was less than 70% for mechanical ventilation time and length of stay in the intensive care unit, suggesting that these scores are appropriately biased toward clinical outcomes as opposed to resource utilization. Both scores performed well, with the Denver MOF score showing greater specificity, which, coupled with its simplicity, makes it an attractive tool for both the research and clinical environments. Basic concepts of each score can probably be combined to produce an improved MOF score.
-
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.
-
The coupled plasma filtration adsorption (CPFA) was developed as an adsorptive hemopurification method aimed at nonselective removal of circulating soluble mediators potentially involved in the pathogenesis of sepsis. We hypothesized that this nonselective hemopurification could protect from detrimental consequences of long-term, volume-resuscitated porcine septic shock. In 16 anesthetized, mechanically ventilated, and instrumented pigs, the hyperdynamic septic shock secondary to peritonitis was induced by intraperitoneally inoculating feces and maintained for 22 h with fluid resuscitation and norepinephrine infusion as needed to maintain MAP above 65 mmHg. ⋯ Similarly, CPFA did not protect from lung and liver dysfunction and even aggravated sepsis-induced disturbances in coagulation and oxidative/nitrosative stress. In this porcine model of septic shock, the early treatment with CPFA was not capable of reversing the sepsis-induced disturbances in various biological pathways and organ systems. Both the efficacy and safety of this method require further rigorous experimental validation in clinically relevant models.