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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Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. ⋯ Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.
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The colon ascendens stent peritonitis (CASP) procedure creates an intestinal leakage of feces, resulting in diffuse peritonitis and polymicrobial sepsis. Mouse models of CASP have been used to study sepsis experimentally. The aim of the present study was to establish CASP sepsis in rats and to provide basic functional characteristics of this model. ⋯ TNF-alpha and IL-10 levels of CASP animals reached a maximum after 12 h. In conclusion, a rat model of CASP sepsis has been established and characterized with regard to alterations in cardiovascular and microcirculatory function as well as plasma cytokine levels. In experimental settings where genetically engineered animals are not required, it will facilitate detailed examination of dynamic changes in integrated organ function during the course of sepsis and the investigation of treatment strategies.
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To investigate the effect of erythropoietin for the management of postresuscitation myocardial dysfunction following asphyxia-induced cardiac arrest. Male adult Wistar rats were used for the prospective controlled animal study. Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. ⋯ Administration of erythropoietin also improved three days survival among those successfully resuscitated. The molecular effects of erythropoietin were shown by activation of its down streaming Akt and ERK 42/44 signaling pathways. EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest.
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We previously reported that beta-SQAG9 liposome, a sulfonoglycolipid extracted from sea urchin intestines, had a protective effect against hepatic ischemia reperfusion (I/R) injury. In this study, we made a detailed investigation of this protective effect and its mechanism. Rats were pretreated either with beta-SQAG9 liposome (treated group) or with phosphate-buffered saline solution (control group). ⋯ On the other hand, there was no apparent difference in the serum levels and the tissue messenger RNA levels of the proinflammatory cytokines between the two groups. Thus, beta-SQAG9 liposome might reduce the hepatic I/R injury by inhibition of the PMN infiltration into the liver parenchyma, which was independent of the regulation of cytokine production. Moreover, we demonstrated that beta-SQAG9 liposome specifically bound to L-selectin on PMN cell surface, which mediated the PMN infiltration. beta-SQAG9 liposome might competitively antagonize L-selectin on PMNs and suppress the subsequent PMN infiltration, resulting in the reduction in I/R injury.
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Transmigration of neutrophil polymorphonuclear leukocytes through the microvascular endothelium is a cardinal event of acute inflammation. In vitro, this process can be restricted by gap junctional intercellular communication, but whether it also occurs in vivo is unknown. Connexin 40 (Cx40) is a gap junctional protein abundantly present in the lung, notably in vascular endothelium. ⋯ The time points for studies with the knockout mice were chosen in such a manner that inflammation was clearly present and Cx40 still largely expressed in wild-type animals. In either model, the development of lung inflammation did not differ between wild-type and Cx40-deficient mice. In conclusion, the pulmonary expression of the Cx40 protein is progressively and markedly decreased in two different murine models of acute lung inflammation, but there is no causal relationship between this process and the pulmonary transmigration of neutrophils.