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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Neonatal asphyxia may lead to cardiac and renal complications perhaps mediated by oxygen free radicals. Using a model of neonatal hypoxia-reoxygenation, we tested the hypothesis that N-acetylcysteine (NAC) would improve cardiac function and renal blood flow. Eighteen piglets (aged 1-4 days old, weighing 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of pulmonary and renal artery flow (cardiac index [CI] and renal artery flow index [RAFI], respectively) and mean blood pressure. ⋯ There were no significant differences in heart rate, pulmonary artery pressure, systemic oxygen uptake, and tissue lipid hydroperoxide levels between groups. No histologic injury was found in the heart or kidney. In this porcine model of neonatal hypoxia and 100% reoxygenation, NAC improved cardiac function and renal perfusion, with improved tissue glutathione content.
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Shock states are associated with an impaired tissue oxygen supply-demand relationship and perturbations within the microcirculation, leading to global tissue hypoxia, finally resulting in multiple-organ failure or even death. Two of the most frequent causes of shock are acute hemorrhage and sepsis. Although the origin and the pathophysiology of hemorrhagic and septic shock are basically different, the involvement of adenosine triphosphate-sensitive potassium (KATP) channels, as an important regulator of vascular smooth muscles tone, plays a pivotal role under both conditions. ⋯ The differences in the species, the comorbidity, and the difficulty in determining the exact onset of shock in clinical practice and, thus, any duration-related alterations in vascular responses and KATP channel activation may explain the discrepancy between the results obtained from experimental and clinical studies. Currently, two of the most relevant problems related to effective KATP blockade in shock states are represented by (1) the dose itself (benefit-risk ratio) and (2) the route of administration (oral vs. i.v.). This review article critically elucidates the published in vivo studies on the role of KATP channel inhibition in both described shock forms and discusses the advantages and the potential pitfalls related to the treatment of human shock states.
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SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia.
Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. ⋯ In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.
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Thermal injury results in reduced plasma levels of arginine (Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. ⋯ Histopathological examinations also indicated a remarkably reduced histopathological scores associated with B + S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but was significantly reduced in the group with Arg. Therefore, L-Arg supplementation improved gas exchange and pulmonary function in ovine after B + S injury via its, at least in part, effect on reduction of oxidative stress through the peroxynitrite pathway.
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Mechanical ventilators are commonly used to support critically ill patients; however, inappropriate ventilator settings might initiate or augment lung injury. To determine whether a large tidal volume (Vt) augments inflammatory responses and neutrophil sequestration in the lungs of rats receiving intratracheal lipopolysaccharides (LPS). Rats received intratracheal instillation of LPS (0.5 mg/kg) followed by 4 h of mechanical ventilation (MV) at 60 strokes per min with a Vt of 10 mL/kg as control MV, or 30 strokes per min with a Vt of 20 mL/kg of body weight as high-volume MV (HMV). ⋯ The ICAM-1 expression in lung tissues was responsible for the synergistic effects of neutrophil sequestration. Synergistic upregulation of IL-1beta production and neutrophil sequestration was attenuated by blocking ICAM-1 by neutralizing antibody pretreatment. High Vt MV in LPS-injured lung causes synergistic production of IL-1beta and sequestration of neutrophil via ICAM-1-dependent effects.