Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality.

Objectives: The purpose of this study was to test whether mitochondrial dysfunction is causative of sepsis sequelae, a mouse model of peritonitis sepsis induced by cecal ligation and perforation. Inhibition of mitochondrial permeability transition was achieved by means of pharmacological drugs and overexpression of the antiapoptotic protein B-cell leukemia (Bcl)-2.

Background: Sepsis is the leading cause of death in critically ill patients and the predominant cause of multiple organ failure.

Evaluation of auto-regulated inspiratory support during rebreathing and acute lung injury in pigs.

Background: Auto-regulated inspiratory support mode (ARIS) is an original closed-loop pressure-support system that regulates the slope ("A") and the initial level ("B") of the applied inspiratory pressure, in order to achieve an optimal minute ventilation under constrained respiratory frequency, tidal volume, and maximum inspiratory airway pressure. The servo-controlled design results in a more or less decreasing applied pressure.

Objective: The aim of this study was to evaluate the ARIS behavior, compared with pressure-support ventilation at a constant applied pressure.

Ventricular myocyte caspases are directly responsible for endotoxin-induced cardiac dysfunction.

Background: Although most of the deleterious effects of sepsis-induced apoptosis have been attributed to increased lymphocyte cell death, caspase activation may directly alter cell function of different organ systems. We postulated that left ventricular (LV) cardiomyocyte caspase activation is directly involved in sepsis-induced heart contractile dysfunction.

Methods And Results: LV cardiomyocytes isolated 4 hours after rat treatment with endotoxin injection (10 mg/kg) displayed major reductions in contractile reserve and myofilament response to Ca2+.

Peroxynitrite decomposition catalysts prevent myocardial dysfunction and inflammation in endotoxemic rats.

Objectives: The aim of this study was to test whether peroxynitrite neutralizers would reduce peroxynitrite accumulation and improve myocardial contractile dysfunction and inflammation in endotoxin-treated rats.

Background: Release of endogenous proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha in response to endotoxin is responsible for the production of large amounts of nitric oxide (NO), which may exert detrimental effects on the myocardium in animal models, isolated hearts, and isolated cardiac myocytes. Recent studies have indicated that many of the deleterious effects of NO are mediated by peroxynitrite, a powerful oxidant generated from a fast diffusion-limited reaction of NO and superoxide anion.

Calpain inhibitors improve myocardial dysfunction and inflammation induced by endotoxin in rats.

Excessive activation of calpains has been implicated in the pathophysiology of inflammation, trauma, and ischemia reperfusion injury. Here, we investigated the effects of calpain inhibition on myocardial dysfunction and inflammation induced by endotoxin in rats. Rats were treated i.

Endotoxin-induced myocardial dysfunction: evidence for a role of sphingosine production.

Objective: To determine whether sphingomyelinase pathway activation would participate in myocardial depression induced by endotoxin.

Design: Randomized, controlled trial.

Setting: Experimental laboratory.

Protective effects of cyclosporin A from endotoxin-induced myocardial dysfunction and apoptosis in rats.

Myocardial depression can be demonstrated following administration of endotoxin. Proposed mechanisms of endotoxin-induced myocardial dysfunction include the release of proinflammatory mediators, focal myocardial ischemia, and the presence of activated leukocytes within the myocardium. Recently, myocardial caspase activation and mitochondria-related apoptotic events (i.