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OBJECTIVE:: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro.DESIGN:: Prospective clinical study followed by cell culture studies.SETTING:: General intensive care unit and research laboratory of a university hospital.SUBJECTS:: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13).INTERVENTIONS:: Cells were exposed to lipopolysaccharide, tumor necrosis factor-α, and interleukin-6.MEASUREMENTS AND MAIN RESULTS:: Patients’ serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-α (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-α and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-α increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels.CONCLUSIONS:: First, patients’ serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-α suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis. [ABSTRACT FROM AUTHOR]

OBJECTIVETo investigate the adrenocortical function in brain-dead patients, potential organ donors.DESIGNProspective study.SETTINGIntensive care units in two teaching hospitals.PATIENTSA total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 ± 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death.INTERVENTIONSIn all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 μg of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 μg/dL after the administration of adrenocorticotropic hormone were defined as responders.MEASUREMENTS AND MAIN RESULTSAfter the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 ± 6.2 vs. 17.0 ± 6.6 μg/dL, p < .001) and stimulated (16.9 ± 6.3 vs. 23.9 ± 5.7 μg/dL, p = .001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p < .001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r = .71, p = .001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = -.37, p = .15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 ± 11.4 vs. 6.8 ± 4.2 μg/dL, p = .003) and stimulated serum cortisol (28.8 ± 9.9 vs. 16.3 ± 4.3 μg/dL, p = .008).CONCLUSIONSAdrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors. [ABSTRACT FROM AUTHOR]