Recherche des anticoagulants de type lupique (cas particulier des patients traités par anti-vitamines K)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Intravenous administration of activated protein C in <it>Pseudomonas</it>-induced lung injury: impact on lung fluid balance and the inflammatory response

Abstract Background Acute lung injury (ALI) induces a coagulation/fibrinolysis imbalance and leads to fibrin deposition. The protein C pathway is an important regulator of the coagulation system and reduces the inflammatory response. The aim of the study was to examine the effects of recombinant human activated protein C (rhAPC) in the early phase of Pseudomonas aeruginosa (Pa)-induced lung injury. Methods The study was conducted in vivo on a rat model of Pa-induced ALI. Continuous intravenous (IV) rhAPC was administrated simultaneously with intratracheal (IT) Pa. We instilled into the airspaces a 5% bovine albumin solution with 1 μ(Ci of 125 I-albumin and injected IV 1 μ(Ci of 111In-albumin to measure lung liquid clearance (LLC) and endothelial injury. Cytokines levels (TNFα and IL-6) and thrombin-antithrombin (TAT) complexes were measured in blood and bronchoalveolar lavage fluid (BALF) at 4 hours. Four groups were compared: control (CTR), pneumonia (PNP) receiving IT Pa (0.5 ml/kg of 1 × 109 cfu), APC: IV rhAPC (300 μg/kg/h), A-PNP: IT Pa /IV rhAPC. Results Alveolar-capillary permeability was increased in the PNP versus the CTR group (0.28 ± 0.08 vs. 0.03 ± 0.01, p Pa-induced ALI led to further injury (0.47 ± 0.17 vs. 0.28 ± 0.08, p = 0.2). The LLC was significantly decreased in the A-PNP group compared to PNP group (9.1 ± (4.3% vs. 33.4 ± 2.6%, p Pa-induced ALI (5.80 ± 0.66, p = 0.07). These findings were associated with a loss of inflammatory response compartmentalization measured by TNFα and IL-6 systemic levels. TAT complexes in BALF were increased in the A-PNP group (23.17 ± 2.89 ng/ml) compared to the CTR group (0.92 ± 0.17 ng/ml, p Conclusion rhAPC reduces LLC following Pa-induced ALI and may influence pulmonary edema formation. The early massive fibrin formation is probably beneficial in ALI limiting both the extent of injury and permeability disorders.</p

Sodium lactate improves renal microvascular thrombosis compared to sodium bicarbonate and 0.9% NaCl in a porcine model of endotoxic shock: an experimental randomized open label controlled study

Abstract Background Sodium lactate seemed to improve fluid balance and avoid fluid overload. The objective of this study was to determine if these beneficial effects can be at least partly explained by an improvement in disseminated intravascular coagulation (DIC)-associated renal microvascular thrombosis. Methods Ancillary work of an interventional randomized open label controlled experimental study. Fifteen female “Large White” pigs (2 months old) were challenged with intravenous infusion of E. coli endotoxin. Three groups of five animals were randomly assigned to receive different fluids: a treatment group received sodium lactate 11.2% (SL group); an isotonic control group received 0.9% NaCl (NC group); a hypertonic control group, with the same amount of osmoles and sodium than SL group, received sodium bicarbonate 8.4% (SB group). Glomerular filtration rate (GFR) markers, coagulation and inflammation parameters were measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn for histological study. Statistical analysis was performed with nonparametric tests and the Dunn correction for multiple comparisons. A p < 0.05 was considered significant. Results The direct immunofluorescence study revealed that the percentage of capillary sections thrombosed in glomerulus were significantly lesser in SL group [5 (0–28) %] compared to NC [64 (43–79) %, p = 0.01] and SB [64 (43–79), p = 0.03] groups. Alterations in platelet count and fibrinogen level occurred earlier and were significantly more pronounced in both control groups compared to SL group (p < 0.05 at 210 and 300 min). The increase in thrombin–antithrombin complexes was significantly higher in NC [754 (367–945) μg/mL; p = 0.03] and SB [463 (249–592) μg/mL; p = 0.03] groups than in SL group [176 (37–265) μg/mL]. At the end of the experiment, creatinine clearance was significantly higher in SL group [55.46 (30.07–67.85) mL/min] compared to NC group [1.52 (0.17–27.67) mL/min, p = 0.03]. Conclusions In this study, we report that sodium lactate improves DIC-associated renal microvascular thrombosis and preserves GFR. These findings could at least partly explain the better fluid balance observed with sodium lactate infusion