Critical care medicine
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Critical care medicine · Oct 2007
Comparative StudySeasonal variations in inflammatory responses to sepsis and stress in mice.
In this study, we analyzed seasonal variations of immunoreactivity using a model of septic shock and a model of immunosuppression induced by chronic stress in mice. ⋯ Our results suggest that seasonal changes of the host's hypothalamus-pituitary-adrenal axis response influence the risk of infection and the susceptibility to stress, which interferes with the outcome after infection.
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Critical care medicine · Oct 2007
Comparative StudyDifferential effects of vasopressin and norepinephrine on vascular reactivity in a long-term rodent model of sepsis.
There is escalating interest in the therapeutic use of vasopressin in septic shock. However, little attention has focused on mechanisms underlying its pressor hypersensitivity, which contrasts with the vascular hyporesponsiveness to catecholamines. We investigated whether a long-term rodent model of sepsis would produce changes in endogenous levels and pressor reactivity to exogenous norepinephrine and vasopressin comparable with those seen in septic patients. ⋯ This long-term animal model demonstrates changes in circulating vasoactive hormones similar to prolonged human sepsis, and decreased pressor sensitivity to norepinephrine. Ex vivo sensitivity to vasopressin agonists was heightened. This model is therefore appropriate for the further investigation of mechanisms underlying vasopressin hypersensitivity, which may include receptor or calcium-handling alterations within the vasculature.
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Critical care medicine · Oct 2007
Coronary artery disease progression is associated with increased resistance of hearts and myocytes to cardiac insults.
To investigate whether coronary artery disease alters vulnerability of hearts and myocytes to cardiac insults. To address this issue, we developed an experimental model of coronary artery disease. ⋯ This work suggests that chronic partial ischemia associated with progression of coronary artery disease preconditions myocytes and hearts against subsequent acute cardiac insults.
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Critical care medicine · Oct 2007
Pumpless extracorporeal lung assist for protective mechanical ventilation in experimental lung injury.
To test the hypothesis that ventilation with 3 mL/kg tidal volume combined with extracorporeal CO2 removal by arteriovenous interventional lung assist reduces ventilator-associated organ injury in experimental acute lung injury when compared with ventilation with 6 mL/kg tidal volume without interventional lung assist. ⋯ Combined ventilation with lower tidal volumes and extracorporeal CO2 removal as compared with traditional low tidal volumes without extracorporeal CO2 removal is not associated with differences in organ injury. Obviously, ventilation with tidal volumes of <6 mL/kg may cause pulmonary de-recruitment when positive end-expiratory pressure is not adequately increased.
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Critical care medicine · Oct 2007
Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure.
Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and subsequently identify new drug targets. ⋯ By applying proteomics to a clinically relevant mouse model of sepsis, we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets.