Heat-inactivation of the human blood product supernatant used in this and in previous studies [9,10,12,28,39] was necessary to prevent widespread thrombus formation and mortality due to non-specific actions of complement and fibrinogen [9,12,39]; however, represents a limitation of these models. As was demonstrated Imatinib Mesylate for sCD40L, heat-inactivation may reduce the concentration of some protein BRMs; however, levels of EGF, ENA-78, GRO-��, IL-8, IL-16 and MCP-1 were all unaffected by heat-inactivation. It remains possible that heat-inactivation may have affected other parameters not investigated, and may have influenced the development of TRALI. The alternative approach of transfusing homologous ovine with PRBC rather than with heat-inactivated supernatant from human PRBC was not used in this study because of the limitations of this alternative approach.

First, while the preparation of ovine PRBC is not technically difficult, this process requires standardisation and validation to ensure that the ovine PRBC provide a suitable model of human PRBC. Second, as has been demonstrated in small animal models [45,47-49], there are likely to be differences between the storage lesions of ovine and human PRBC. Detailed comparative data comparing the storage lesions of ovine PRBC and human PRBC are, therefore, essential to validate an ovine model of homologous transfusion for the study of effects related to the age of blood. While future studies are planned to address these limitations of homologous transfusion models, it was felt that, at the present time, the transfusion of heat-inactivated supernatant from human blood products, provided a more relevant clinical model of TRALI.

PRBC that have not undergone pre-storage leucoreduction comprise a significant proportion of the PRBC used in the USA (approximately 20% of the approximately 17 million PRBC transfused in 2009) [50]. Hence, the findings of this study are of particular clinical relevance to the USA and other countries in which universal pre-storage leucoreduction of blood products has not yet been implemented. Leucoreduction has been shown to reduce the concentration of leucocyte-derived factors in the storage lesion of cellular blood products [41]; however, whether it also reduces the risk of TRALI remains a matter of conjecture based upon current evidence [7,12,18,51].

Of note, analyses of 89 TRALI cases from two tertiary care medical centres in the USA [7] and AV-951 of 60 TRALI cases in The Netherlands [8] failed to demonstrate any association between the length of storage of leucoreduced PRBC and TRALI, although these analyses may have been confounded by the presence of leucocyte antibodies in a proportion of leucoreduced PRBC. Hence, the importance of the present study, and the ovine model, as a historical marker allowing for further investigation of the effects of leucoreduction upon TRALI pathogenesis.

This may promote, at least in part, neuroprotection. (iii) The volatile anesthetic sevoflurane, when administered during reperfusion after successful CPR, did not confer statistically significant additional anti-inflammatory effects in the above setting.Key messages? Global cerebral ischemia following selleck Erlotinib cardiac arrest results in up-regulation of local pro-inflammatory cytokines expression.? Mild hypothermia after cardiac arrest attenuates cerebral inflammatory response.? Sevoflurane does not confer additional anti-inflammatory effects.? Further studies on the relationship between cerebral inflammatory response and post-resuscitation cerebral dysfunction are warranted.

AbbreviationsBL: baseline; CPR: cardiopulmonary resuscitation; ELISA: enzyme-linked immunosorbent assay; HT: hypothermia; ICAM-1: intercellular adhesion molecule-1; IL: interleukin; LAD: left anterior descending (coronary artery); NT: normothermia; ROSC: return of spontaneous circulation; RT-PCR: reverse transcriptase polymerase chain reaction; SEV: sevoflurane; TIVA: total intravenous anesthesia; TNF��: tumor necrosis factor ��; VF: ventricular fibrillation.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsPM, KDZ and BB conceived and designed the experiments. PM, MG, KDZ and MA performed the experiments. MG, MA, RL, NF, JH and KZ analyzed the data. PM, KDZ, MA and BB wrote the paper. All authors read and approved the final manuscript.Supplementary MaterialAdditional file 1:Extended Method section – Quantitative real-time RT-PCR.

Detailed description of quantitative real-time RT-PCR, primer sequences and TaqMan probes.Click here for file(80K, doc)NotesSee related commentary by Zhang, http://ccforum.com/content/14/2/137AcknowledgementsThis work has been supported by the German Interdisciplinary Association of Critical Care Medicine (PM) and by the German Research Foundation (BB). The founders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are indebted to H. Fiedler, B. Zastrow, B. Kuhr, and V. Haensel-Bringmann for technical assistance. We thank C. Rodde, S. Piontek, M. Koelln, G. Jopp, Prof. I. Cascorbi and M. Ufer for laboratory analysis.

The manuscript was presented in part at the Annual Meeting of the Society of Neurosurgical Anesthesia and Critical Care, Orlando, FL, USA, 17th October 2008, and at the 3rd International Hypothermia Symposium, Lund, Sweden, 5th September GSK-3 2009.
Despite relevant improvements in the treatment of acute respiratory distress syndrome (ARDS) mortality remains high. The estimated annual number of deaths due to acute lung injury was calculated as 74,500 for the US in a population-based study in 2005 [1]. Mortality in severe ARDS with a high lung-injury score (>3.5) and a low oxygenation index is reported to be considerably higher and may reach more than 80% [2,3].

In this line, cyclic collapse/reopening has also been recognized as a determinant of VILI [43].Cardiac output, stroke volume, and ejection fraction selleck chem Enzalutamide were increased during hypervolemia. Increased pulmonary perfusion may also directly damage the lungs. In a model of VILI, Lopez-Aguilar and colleagues [44] have shown that the intensity of pulmonary perfusion contributes to the formation of pulmonary edema, adverse distribution of ventilation, and histological damage.In hypervolemia, we observed an increase in IL-6 mRNA expression in lung tissue, but PCIII mRNA expression did not change, which may be explained by the absence of hyperinflation [12]. Additionally, VCAM-1 and ICAM-1 mRNA expressions were elevated in HYPER group suggesting endothelial activation due to vascular mechanical stretch.

Despite increased lung injury and activation of the inflammatory process, hypervolemia was not associated with increased distal organ injury. Furthermore, hypovolemia and normovolemia did not contribute to distal organ injury, but rather protected the lungs from further damage. Our observation supports the claim that the lungs are particularly sensitive to fluid overload [45]. Lung-borne inflammatory mediators can spill over into the circulation and promote distal organ injury. However, when protective mechanical ventilation is used, decompartmentalization of the inflammatory process is limited [46].Interactions between recruitment maneuvers and volemiaThe low VT and airway pressure concept has been shown to decrease the mortality in ALI/ARDS patients [1].

Given the uncertain benefit of RMs on clinical outcomes, the routine use of RMs in ALI/ARDS patients cannot be recommended at this time. However, RMs have been shown to improve oxygenation without serious adverse events [11]. Furthermore, other papers suggested that RMs may be useful before PEEP setting, after inadvertent disconnection of the patient from the mechanical ventilator or airways aspiration [47]. Finally, RMs have been proposed to further improve respiratory function in ALI/ARDS patients in prone position [48]. Thus, in our opinion, their judicious use in the clinical setting may be justified.In our animals, RMs reduced alveolar collapse and increased normal aerated tissue independent of the degree of volemia. Along this line, experimental and clinical studies have shown that improvement in lung aeration is associated with better lung mechanics [49-51].

RMs improved oxygenation during hypervolemia, probably because of the higher amount of collapsed lung tissue, which may increase the effectiveness of RMs reversing atelectasis and decreasing Brefeldin_A intrapulmonary shunt. Gattinoni and colleagues [51] have shown that the beneficial effects of RMs are more pronounced in patients with higher lung weight and atelectasis.