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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Recent studies have documented the association of mesenteric lymphatic route with adult respiratory distress syndrome and multiple organ failure after hemorrhagic shock. However, the mediators and mechanisms of the toxic effects of mesenteric lymph remain unclear. This study aimed to identify mediators or biomarkers in the mesenteric lymph through comparative proteomic analysis. ⋯ The deregulation of these proteins was confirmed by Western blots. Most of these altered proteins are functionally implicated in tissue inflammation. The findings of this study provide a starting point for investigating the functions of these proteins in hemorrhagic shock-induced lung injury and hold great promise for the development of potential therapeutic interventions.
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Comparative Study
Effects of tramadol and buprenorphine on select immunologic factors in a cecal ligation and puncture model.
Sepsis research relies on animal models. The models that most closely resemble clinical disease, such as cecal ligation and puncture, require surgery. After surgery, analgesics may not be included in experimental protocols because of concern over effects on inflammatory responses. ⋯ Again,differences were observed between the treatments. The results suggest that judicious and limited use of some analgesics may not dramatically affect the outcome of similarly conducted cecal ligation and puncture studies when compared with those not using analgesics. However, when different analgesics are used, comparisons between studies may be complicated.
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Comparative Study
Direct cardiac effects of dobutamine, dopamine, epinephrine, and levosimendan in isolated septic rat hearts.
In septic patients, myocardial depression-the so-called septic cardiomyopathy-needing inotropic support is common. The aim of this study was to compare the dose-responsive electrophysiological and mechanical properties concerning metabolic effects of clinically available inotropic agents in an isolated septic rat heart model. After 20 h of incubation, both sham-operated and septic (cecal ligation and single puncture) hearts from male Wistar rats (n = 64) were isolated and received dobutamine, dopamine, epinephrine, or levosimendan at concentrations of 10 to 10 M. ⋯ However, cardiac efficiency was significantly improved in the epinephrine-treated septic hearts. With the drug-induced increase in cardiac performance, the myocardial oxygen supply-demand ratio decreased proportionally in the epinephrine-, dobutamine-, and dopamine-treated septic hearts. However, epinephrine showed the most favorable results with regard to cardiac efficiency, and levosimendan showed no beneficial effect in septic hearts with regard to efficiency in this study.
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NO has been implicated in the pathogenesis of septic shock. However, the role of NO synthase 3 (NOS3) during sepsis remains incompletely understood. Here, we examined the impact of NOS3 deficiency on systemic inflammation and myocardial dysfunction during peritonitis-induced polymicrobial sepsis. ⋯ The impaired Ca handling of cardiomyocytes isolated from NOS3KO mice subjected to CASP was associated with depressed mitochondrial ATP production, a determinant of the Ca cycling capacity of sarcoplasmic reticulum Ca-ATPase. The NOS3 deficiency-induced impairment of the ability of mitochondria to produce ATP after CASP was at least in part attributable to reduction in mitochondrial respiratory chain complex I activity. These observations suggest that NOS3 protects against systemic inflammation and myocardial dysfunction after peritonitis-induced polymicrobial sepsis in mice.