What's New in Shock, August 2011?

The article by Schuetz et al. (1) describes hypotensive patients in the emergency department with sepsis or nonsepsis conditions. It appears in the septic patients that their condition was associated with the appearance of endothelial cell biomarkers, s(soluble) E-selectin and sFLT-1 (the soluble receptor for vascular endothelial growth factor) and that these markers were fairly reliable indicators of sepsis, whereas other endothelial markers (such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, vascular endothelial growth factor, or plasminogen activator inhibitor 1) were less reliable markers. To what extent the presence of sE-selectin and sFLT-1 can be used as prognostic indicators of sepsis during treatment remains to be determined. The report by Park et al. (2) has a focus on plasma levels of the N-terminal proYbrain natriuretic peptide (NT-proBNP) in patients with acute lung injury or acute respiratory distress syndrome, the clinical presentations being septic shock and sequential organ failure associated with assessment (SOFA) scores. In nonsurvivors, NT-proBNP scores were significantly elevated on days 1 and 2 when compared with levels in survivors. There were parallel changes in 28-day mortality. It is suggested that the combination of NT-proBNP levels and SOFA scores may be of greater prognostic value as compared with SOFA scores alone. It has been known for some time that heart rate variability (HRV) occurs in humans infused with LPS and that this may correlate with the ensuing inflammatory response. In the study by Kox et al. (3), 40 healthy adult humans were infused with LPS. Of this group, 12 subjects were reinfused with LPS 2 weeks later. Somewhat unexpectedly, the HRV response did not correlate with the magnitude of the inflammatory response (plasma cytokines), despite large changes in HRV values. Interestingly, in subjects exposed to a second infusion of LPS, HRV changes were robustly expressed again, but plasma levels of cytokines were reduced. Accordingly, HRV responses do not correlate with the inflammatory responses (plasma cytokine levels) after infusion of LPS into humans. The role of gut-derived, biologically active products and the ability of these factors to trigger a systemic inflammatory response have been a topic of considerable debate for some time. The report by Willoughby et al. (4) deals with studies of 8 patients undergoing elective abdominal aortic resection, during which time there was aortic cross clamping, resulting in bowel ischemia followed by reperfusion. Numerous cytokines were measured in central venous and mesenteric blood plasma samples, before and after aortic cross-clamping and after reperfusion. Neither central nor mesenteric venous blood contained detectable bacterial DNA, although it is not clear if the same would be found in sequential samples of plasma. Neither the central nor the mesenteric plasma samples caused apoptosis or necrosis of human umbilical vein endothelial cell monolayers exposed to these samples, nor was there evidence of upregulation of intercellular adhesion molecule 1 on human umbilical vein endothelial cells, although the plasma samples caused increased expression of RAGE (receptor for advanced glycation products) on these cells. The authors concluded that abdominal aortic resection raised plasma cytokine levels in both mesenteric and central venous blood, but the same samples lacked evidence for the presence of either Btoxic endothelial factors[ or Bgut-derived microorganisms.[ Obviously, this report needs to be considered in terms relevant to other human conditions. Whether a similar pattern would be found in patients undergoing emergency abdominal aortic resection would be an important subsequent study, but under such conditions, the frequent need for massive blood replacement greatly complicates interpretation of data. On the other hand, the current study adds to increasing doubts about the role of gut bacterial translocations in the setting of shock and sepsis. Smoke inhalation is known to cause fibrin deposition in the lung. In the report by Midde et al. (5), pigs were ventilated and exposed to wood bark smoke, which induced acute lung injury. As expected, extensive fibrin deposition occurred in the alveolar compartment, in small and large airways, and in the subpleural space. When pleural mesothelial cells or alveolar type II cells were exposed to an extract of wood bark smoke, mRNA for plasminogen activator inhibitor 1 was stabilized with attendant enhancement protein expression, presumably due to dissociation from plasminogen activator inhibitor 1 mRNA of 6-phospho-D-gluconate NADP oxidoreductase. These events may relate to extensive intrapulmonary deposition of fibrin occurring after smoke inhalation. In the report of Thakkar et al. (6), acute lung injury developed in mice following hemorrhagic shock and subsequent cecal ligation and puncture (CLP). End points were levels in lung homogenates of TNF-!, monocyte chemotactic protein 1 (CCL2), IL-6, and IL-10. Interventions included none or use of siRNA for FasL, or siRNA for green fluorescent protein. Only the siRNA to FasL was protective (reduction in mediator levels as well as reduced lung levels of myeloperoxidase), provided it was administered intratracheally. Intravenous administration had no measurable effects. These studies suggest that local (intrapulmonary) production of FasL triggers caspase 3 activation, followed by apoptosis of pulmonary cells. The combination of local (flank) thermal injury and smoke inhalation in sheep is well known to induce a variety of complications, especially in lung. The Galveston group of Bartha