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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This study tested the hypothesis that a novel mitochondria-targeted SS-31 peptide attenuates the burn injury-induced apoptosis and endoplasmic reticulum stress and improves insulin sensitivity in the skeletal muscle. Following 30% total body surface area burn or sham burn, mice were injected daily with SS-31 peptide (5 mg/kg body weight), and the rectus abdominis muscles collected on postburn days 1, 3, and 7. The tissues were subjected to various biochemical and immunohistochemical analyses. ⋯ Burn injury-induced increases in the levels of two endoplasmic reticulum stress markers, binding immunoglobulin protein and protein disulfide isomerase, were significantly decreased by the SS-31 peptide treatments on postburn day 7 and on day 3 for binding immunoglobulin protein as well (P < 0.05). The effects of SS-31 appear to be, in part, due to its ability to reduce oxidative stress in burned mice, evidenced by reduced expression of oxidized proteins that were clearly evident on postburn day 7. Our results demonstrate a possible therapeutic potential of SS-31 peptide to ameliorate the adverse effects of burn injury in skeletal muscle.
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The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO(2))-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO(2)-driven resuscitation including fluids, norepinephrine and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress during a clinically resembling experimental model of septic shock. Eighteen anesthetized and catheterized pigs (35-45 kg) were submitted to peritonitis by fecal inoculation (0.75 g/kg). ⋯ Treatment strategies did not significantly modify oxidative stress parameters. Thus, an approach aiming SvO(2) during sepsis improves hemodynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects associated with this strategy may be related to other mechanisms.
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Procalcitonin (PCT) concentration of greater than 10 ng/mL is compatible for septic shock. Its predictive value for survival is not well established, mainly because of much overlap and variation of PCT in this condition. We hypothesized that dynamic change of PCT, rather than PCT itself, is predictive of hospital survival when greater than 10 ng/mL. ⋯ Procalcitonin of initial, subsequent measurements, and dynamics significantly correlated with their counterparts of SOFA score. In conclusion, significant decrease in PCT concentration, rather than PCT concentration itself, may be a useful indicator of survival in septic shock patients when PCT concentration is greater than 10 ng/mL. Procalcitonin concentration highly correlated with the SOFA score in septic shock patients even when the PCT concentration is greater than 10 ng/mL.
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Pulse pressure variation (PPV) is a promising predictor for volume responsiveness. However, recent studies have criticized its validity during small tidal volume (TV) ventilation. The present study evaluated the influence of pressure control level (PCL) on PPV. ⋯ The PPV as well as the slopes of the trend lines decreased from hypovolemic stages toward hypervolemic stages. Pulse pressure variation responds rapidly to change in ventilator setting and is linearly correlated with the PCL and TV. These characteristics may have important applications in critical care to improve the interpretation of PPV in accord to different ventilator settings.
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Severe sepsis and septic shock are often accompanied by acute cardiovascular depression. Lipopolysaccharide (LPS) signaling via Toll-like receptor 4 (TLR4) can induce septic organ dysfunction. The aim of this study was to elucidate the in vivo impact of pharmacological TLR4 antagonism on LPS-induced cardiovascular depression using eritoran tetrasodium (E5564). ⋯ Furthermore, cardiac and aortic inducible nitric oxide synthetase mRNA levels were significantly increased 6 h after LPS application. This effect was reduced in the presence of eritoran. In summary, the beneficial influence of eritoran on cardiovascular function in vivo seems to rely mainly on reduction of LPS-induced inducible nitric oxide synthetase expression as well as on attenuated cytokine expression in the vascular wall.