Generally, in contrast with the normal controls, significantly more distinct

This difference is explained by one rat with an plasma creatinine level, substantially higher than the average level of plasma creatinine in rats sub jected to MV after acid instillation. The degree of sepsis in our model was relatively mild and of short duration prior MAPK 機能 to MV. This explains the ab sence of lung injury after sepsis and HVT. Although CLP induced polymicrobial sepsis is one of the best and most widely used animal models for sepsis and organ in jury the bacterial inoculum is unknown and severity may vary accordingly. CLP induced sepsis can also cause lung injury, mainly targeting the pulmonary endothelium. Campos et al, reported a 24 hr mortality rate of 50% after sepsis, whereas we observed a 6% mortality rate indicating a less severe sepsis with likely less endothe lial damage in our study.<br><br> The more severely injured pul monary endothelium found by Campos et al, is highlighted by the increased wet to dry lung weight ratio. The increased endothelial damage may have attracted more polymorphonuclear granulocyes, including neutrophils MK-1775 臨床試験 with subsequently more oxidative stress than in our study where the pulmonary endothelium was not damaged. The additional effect of HVT MV on lung injury in our study was limited, similar to others where they found that a VT of more than 15 ml kg was necessary to injure the lungs dur ing sepsis. In contrast to sepsis, MV following acid instillation in our study did not cause kidney apoptosis. Previous animal studies of acid instillation induced lung injury followed by injurious MV reported conflicting findings on kidney injury and apoptosis.<br><br> Imai et al. showed that after 8 hrs of MV in rabbits following intra tracheal acid instillation HVT MV in creased kidney epithelial cell apoptosis 6 fold compared ms-275 構造 to a LVT MV. After 4 hrs, this was not associated with increased plasma creatinine levels, but after 8 hrs, creatin ine was higher after HVT. In contrast, Hoag et al, did not observe kidney apoptosis after 5 hrs of MV with HVT following acid instillation or sham treatment in dogs. Furthermore, in this study, various measure ments of kidney function did not differ between the groups. Hoag et al. suggested that in the study by Imai et al. the mean arterial pressure was maintained be tween 55 60 mmHg. This low mean arterial pressure may account for some of the alterations observed in plasma creatinine as a consequence of reduced renal blood flow, which was not measured.<br><br> Species differences and se verity of lung injury may have affected the differences in outcome in these studies. This study has some limitations. Since rat chest wall and lung mechanics differ from the human situation these results cannot be translated to the human situation directly. We used a VT of 15 ml kg with no PEEP as a proof of concept. These settings are not used in humans since they are associated with increased lung injury and death in patients with ARDS. However, we observed increased renal apoptosis after HVT in the absence of functional and histological lung injury. This suggests that during sepsis without lung injury MV with settings that do not directly injure the lung there may be effects on the kidney, especially since VTs greater than 6 ml kg are still used.