Delphine Corseaux

Comparison of Blood Activation in the Wound, Active Vent, and Cardiopulmonary Bypass Circuit

BACKGROUNDnDuring cardiopulmonary bypass, aspirated blood exhibits strong activation features, but the triggering event remains unclear. Contact of blood with the pericardial cavity and surgical wound has been advocated as the main trigger, but suction forces are also considered as a possible contributor. We thus designed a study to identify the possible causes involved in this activation.nnnMETHODSnIn 10 patients, we analyzed hemostasis activation markers and inflammatory mediators in blood collected in the pericardial cavity and in blood actively aspirated from the left ventricle without any contact with the pericardial cavity. In addition, the same variables were determined in blood sampled in the cardiopulmonary bypass circuit.nnnRESULTSnMarkers of tissue factor pathway activation and of thrombin generation, microparticles, free hemoglobin, interleukin 6, and tumor necrosis factor-alpha were significantly increased in pericardial samples as compared with the left ventricle and cardiopulmonary bypass circuit samples. All measured variables were similar between left ventricle and cardiopulmonary bypass samples, except free hemoglobin, interleukin 6, and microparticle levels, which were significantly higher in the left ventricle.nnnCONCLUSIONSnBlood contact with the pericardial cavity induces strong hemolysis, inflammatory mediator release, and coagulation activation, driven by tissue factor pathway activation. By contrast, suction forces applied to left ventricular blood poorly contribute to blood trauma and activation. Comparison of pericardial and left ventricular blood shows that contact with the pericardial cavity, and not suction forces, is the leading cause of blood activation. The specific trigger for blood trauma and activation present in the pericardial cavity remains to be identified.

Inflammation triggers colony forming endothelial cell mobilization after angioplasty in chronic lower limb ischemia

rapid microscale procedure for the simultaneous preparation of cytoplasmic RNA, nuclear DNAbinding proteins and enzymatically active luciferase extracts. Nucleic Acids Res 1991; 19: 5080. 10 Picketts DJ, Mueller CR, Lillicrap D. Transcriptional control of the factor IX gene: analysis of five cis-acting elements and the deleterious effects of naturally occurring hemophilia B Leyden mutations. Blood 1994; 84: 2992–3000. 11 Carew JA, Pollak ES, High KA, Bauer KA. Severe factor VII deficiency due to a mutation disrupting an Sp1 binding site in the factor VII promoter. Blood 1998; 92: 1639–45.

Activated protein C increases sensitivity to vasoconstriction in rabbit Escherichia coli endotoxin-induced shock

IntroductionThe aim of this study was to investigate the effects of activated protein C (aPC) on vascular function, endothelial injury, and haemostasis in a rabbit endotoxin-induced shock model.MethodThis study included 22 male New Zealand rabbits weighing 2.5 to 3 kg each. In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors and monocyte tissue factor (TF) expression were performed 5 days (D5) after onset of endotoxic shock (initiated by 0.5 mg/kg intravenous bolus of Escherichia coli lipopolysaccharide (LPS)) with or without treatment with aPC injected as an intravenous 2 mg/kg bolus 1 hour after LPS (LPS+aPC group and LPS group, respectively).ResultsLPS decreased the sensitivity to phenylephrine (PE) in aortic rings without endothelium (E-) when compared to E- rings from the control group (p < 0.05). This was abolished by NG-nitro-L-arginine methyl ester and not observed in E- rings from aPC-treated rabbits. Although aPC failed to decrease monocyte TF expression in endotoxinic animals at D5, aPC treatment restored the endothelium-dependent sensitivity in response to PE (2.0 ± 0.2 μM in rings with endothelium (E+) versus 1.0 ± 0.2 μM in E- rings (p < 0.05) in the LPS+aPC group versus 2.4 ± 0.3 μM in E+ rings versus 2.2 ± 0.2 μM in E- rings (p value not significant), in the LPS group). Endotoxin-induced de-endothelialisation was reduced by aPC at D5 (28.5 ± 2.3% in the LPS+aPC group versus 40.4 ± 2.4% in the LPS group, p < 0.05).ConclusionThese data indicate that aPC increased the sensitivity to a vasoconstrictor agent (PE) associated with restoration of endothelial modulation, and protected against endothelial histological injury in endotoxin-induced shock. It failed to inhibit TF expression at D5 after LPS injection.

Inhibition of tissue factor-factor VIIa proteolytic activity blunts hepatic metastasis in colorectal cancer.

BACKGROUNDnExpression of the principal initiator of coagulation, tissue factor (TF), by colorectal cancer (CRC) cells is involved in tumoral angiogenesis and metastasis progression, after binding of factor VIIa (FVIIa) to TF and generation of TF-FVIIa activity. We thus hypothesized that inhibition of the TF pathway by active site-blocked FVIIa (FFR-FVIIa) may prevent the development of hepatic metastasis in CRC.nnnMETHODSnRat tumoral cells (DHDK12 proB cells) expressing high levels of TF were injected in the portal vein in syngenic BDIX rats. Rats received intraperitoneal injection of either FFR-FVIIa, from d 3 to d 7 (adjuvant treatment) (n = 19), or solvent buffer (n = 18) (control group). Additionally, cancer cells were infused subcutaneously in 20 other rats, which were assigned to FFR-FVIIa adjuvant treatment (n = 10), or buffer treatment (n = 10). Macroscopic and histological analysis was performed at d 14.nnnRESULTSnIn the control group, infusion of cancer cells resulted in development of macroscopic hepatic tumors in 17/18 rats. In the adjuvant FFR-FVIIa group, macroscopic hepatic tumors were visible on the liver surface in 3/19 rats (P = 0.002 versus control). All rats with subcutaneous injection of proB cells exhibited macroscopic tumors, with no significant difference between the control and the treated ones.nnnCONCLUSIONnInhibition of the proteolytic activity of TF-FVIIa complex blunted hematogenous hepatic metastasis, suggesting that TF-FVIIa is a relevant target for the prevention of hepatic metastasis in CRC. TF-blocking agents should be investigated as adjuvant treatment in this setting.