5). In the HYPER group, RMs led to increased TUNEL positive cells (Table (Table55 and Figure Figure5),5), but not of kidney, liver, and small intestine villous cells.Table 5Cell apoptosisFigure 5Representative photomicrographs of lung stained with H&E (left panels) and TUNEL (right panels). Animals were randomly assigned to hypovolemia (HYPO), normovolemia (NORMO) or hypervolemia selleckchem (HYPER) with recruitment maneuver (RM-CPAP) or not (NR). …In NR groups, IL-6, VCAM-1, and ICAM-1 mRNA expressions were higher in HYPER compared with the HYPO and NORMO groups. VCAM-1 and ICAM-1 expressions were also higher in HYPO compared with NORMO, reduced after RMs in HYPO, but augmented in NORMO group. In HYPER group, VCAM-1 expression rose after RMs but ICAM-1 remained unaltered.
IL-6, IL-1��, PCIII, and caspase-3 mRNA expressions increased after RMs in HYPER group, but not in NORMO and HYPO groups (Figure (Figure66).Figure 6RT-PCR analysis of caspase-3, IL-6, IL1-��, type III procollagen (PCIII), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) mRNA expressions in lung tissue. Animals were randomly assigned to hypovolemia …DiscussionIn the present study, we examined the effects of RMs in an experimental sepsis-induced ALI model at different levels of MAP and volemia. We found that: 1) hypervolemia increased lung W/D ratio and alveolar collapse leading to an impairment in oxygenation and Est,L. Furthermore, hypervolemia was associated with alveolar and endothelium damage as well as increased IL-6, VCAM-1 and ICAM-1 mRNA expressions in lung tissue; 2) RMs reduced alveolar collapse regardless of volemic status.
In hypervolemic animals, RMs improved oxygenation above the levels observed with the use of PEEP, but were associated with increased lung injury and higher inflammatory and fibrogenic responses; and 3) volemic status associated or not with RMs had no effects on distal organ injury.Methodological aspectsTo our knowledge, this is the first study investigating the combined effects of RMs and volemic status in sepsis-induced ALI. We used a CLP model of sepsis because it is reproducible and leads to organ injury that is comparable with that observed in human surgical sepsis [28,29].Volemic status was assessed by echocardiography. It has been shown that echocardiography provides valuable information on preload and cardiac output [30,31].
An inspired oxygen fraction of 0.3 was used throughout the study to minimize possible iatrogenic effects of high inspiratory oxygen concentration on the lung parenchyma [32]. To avoid possible confounding effects of ventilation/perfusion Cilengitide mismatch on the interpretation of the gas-exchange data, inspiratory oxygen fraction was increased to 1.0 just before arterial blood sampling [33]. All animals underwent protective mechanical ventilation to minimize possible interactions between conventional mechanical ventilation, volemic status, and RMs.