The Secretome Deregulations in a Rat Model of Endotoxemic Shock.

INTRODUCTION: Septic shock is a systemic inflammatory response syndrome associated with organ failures. Earlier clinical diagnosis would be of benefit to a decrease in the mortality rate. However, there is currently a lack of predictive biomarkers. The secretome is the set of proteins secreted by a cell, tissue, or organism at a given time and under certain conditions. The plasma secretome is easily accessible from biological fluids and represents a good opportunity to discover new biomarkers that can be studied with nontargeted "omic" strategies. AIMS: To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model. METHODS: Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP) and heart rate (HR) monitoring and blood sampling at different time points (T0 and T50 or T0 and T90, with EDTA and protease inhibitor). Samples were prepared for large-scale tandem mass spectrometry (MS-MS) based on a label-free quantification to allow identification of the proteins deregulated upon endotoxemic conditions. A Gene Ontology (GO) analysis defined several clusters of biological processes (BP) in which the DEP are involved. RESULTS: Ninety minutes after shock induction, the LPS group presents a reduction in MAP (-45%, p < 0.05) and increased lactate levels (+27.5%, p < 0.05) compared to the control group. Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation. CONCLUSION: This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis.

Cost of red blood cell transfusion; evaluation in a French academic hospital.

OBJECTIVES: The economic impact of Patient blood management (PBM) must be assessed beyond the acquisition cost of blood products alone. The estimate of indirect costs may vary depending on the organization and the elements taken into account. The transposition of data from the literature into a specific local context is therefore delicate. The objective of this work was to evaluate the overall cost of red blood cell concentrate (RBC) transfusion from a French healthcare establishment point of view. METHODS: We carried out an activity based costing analysis in our hospital for the year 2018. The steps of the transfusion process and additional costs were detailed and cumulated (resource consumption, labor time, frequency) to populate the ABC model. Several scenarios were developed focusing either on RBC, all blood products or the surgical activity, and a univariate sensitivity analysis was conducted. RESULTS: The average total cost of transfusion, including acquisition cost, was 339,64 euros per RBC transfused. The cost of administration was 138.41 euros/RBC. Focusing only on surgical activities increased this cost (152.43 euros) while taking all blood products into account reduced it (92.49 euros). CONCLUSION: The difference in our results with the literature confirms the local variability in the cost of transfusion, which may affect the economic impact of PBM. Our study related to the specific context of a single French institution has limitations that a multicenter study would clarify in order to carry out economic modelling of transfusion optimization and alternatives and to guide the choice of PBM strategies at the national level.

Change in end-tidal carbon dioxide outperforms other surrogates for change in cardiac output during fluid challenge.

Background: During fluid challenge, volume expansion (VE)-induced increase in cardiac output (Δ VE CO) is seldom measured. Methods: In patients with shock undergoing strictly controlled mechanical ventilation and receiving VE, we assessed minimally invasive surrogates for Δ VE CO (by transthoracic echocardiography): fluid-induced increases in end-tidal carbon dioxide (Δ VE E'CO2 ); pulse (Δ VE PP), systolic (Δ VE SBP), and mean systemic blood pressure (Δ VE MBP); and femoral artery Doppler flow (Δ VE FemFlow). In the absence of arrhythmia, fluid-induced decrease in heart rate (Δ VE HR) and in pulse pressure respiratory variation (Δ VE PPV) were also evaluated. Areas under the receiver operating characteristic curves (AUC ROC s) reflect the ability to identify a response to VE (Δ VE CO ≥15%). Results: In 86 patients, Δ VE E'CO2 had an AUC ROC =0.82 [interquartile range 0.73-0.90], significantly higher than the AUC ROC for Δ VE PP, Δ VE SBP, Δ VE MBP, and Δ VE FemFlow (AUC ROC =0.61-0.65, all P <0.05). A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) had good positive (5.0 [2.6-9.8]) and fair negative (0.29 [0.2-0.5]) likelihood ratios. The 16 patients with arrhythmia had similar relationships between Δ VE E'CO2 and Δ VE CO to patients with regular rhythm ( r 2 =0.23 in both subgroups). In 60 patients with no arrhythmia, Δ VE E'CO2 (AUC ROC =0.84 [0.72-0.92]) outperformed Δ VE HR (AUC ROC =0.52 [0.39-0.66], P <0.05) and tended to outperform Δ VE PPV (AUC ROC =0.73 [0.60-0.84], P =0.21). In the 45 patients with no arrhythmia and receiving ventilation with tidal volume <8 ml kg -1 , Δ VE E'CO2 performed better than Δ VE PPV, with AUC ROC =0.86 [0.72-0.95] vs 0.66 [0.49-0.80], P =0.02. Conclusions: Δ VE E'CO2 outperformed Δ VE PP, Δ VE SBP, Δ VE MBP, Δ VE FemFlow, and Δ VE HR and, during protective ventilation, arrhythmia, or both, it also outperformed Δ VE PPV. A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) indicated a likely response to VE.

Blood pressure monitoring during arrhythmia: agreement between automated brachial cuff and intra-arterial measurements.

BACKGROUND: Since arrhythmia induces irregular pulse waves, it is widely considered to cause flawed oscillometric brachial cuff measurements of blood pressure (BP). However, strong data are lacking. We assessed whether the agreement of oscillometric measurements with intra-arterial measurements is worse during arrhythmia than during regular rhythm. METHODS: Among patients of three intensive care units (ICUs), a prospective comparison of three pairs of intra-arterial and oscillometric BP readings was performed among patients with arrhythmia and an arterial line already present. After each inclusion in the arrhythmia group, one patient with regular rhythm was included as a control. International Organization for Standardization (ISO) standard validation required a mean bias <5 (sd 8) mm Hg. RESULTS: In 135 patients with arrhythmia, the agreement between oscillometric and intra-arterial measurements of systolic, diastolic and mean BP was similar to that observed in 136 patients with regular rhythm: for mean BP, similar mean bias [-0.1 (sd 5.2) and 1.9 (sd 5.9) mm Hg]. In both groups, the ISO standard was satisfied for mean and diastolic BP, but not for systolic BP (sd >10 mm Hg) in our ICU population. The ability of oscillometry to detect hypotension (systolic BP <90 mm Hg or mean BP <65 mm Hg), response to therapy (>10% increase in mean BP after cardiovascular intervention) and hypertension (systolic BP >140 mm Hg) was good and similar during arrhythmia and regular rhythm (respective areas under the receiver operating characteristic curves ranging from 0.89 to 0.96, arrhythmia vs regular rhythm between-group comparisons all associated with P>0.3). CONCLUSIONS: Contrary to widespread belief, arrhythmia did not cause flawed automated brachial cuff measurements.

Increased ß2-adrenergic vasorelaxation at the early phase of endotoxemic shock in rats.

BACKGROUND AND PURPOSE: The early management of the cardiovascular dysfunction of septic shock is critical as it is associated with a poor outcome. Although the use of catecholamines is a common therapy in this syndrome, no data are available on the involvement of ß-adrenoceptor (ß-AR) subtypes and only few studies report an alteration of ß-adrenergic-induced vasodilation in septic shock. The purpose of the study was to evaluate vascular ß1, ß2 and ß3-AR expression and function in an endotoxemic rat model. EXPERIMENTAL APPROACH: Endotoxemia was induced in rats by intravenous injection of lipopolysaccharide (LPS). ß1, ß2 and ß3-AR mRNA expression was evaluated by RT-PCR in aorta and vascular ß1, ß2 and ß3-AR responses were determined on conducting (aorta) and/or resistance (mesenteric and renal) arteries by constructing relaxation curves in response to different ß-AR agonists. RESULTS: The maximal effect of isoproterenol decreased by 31 to 61% in the three vascular beds of LPS-treated rats compared to controls. In aortas from LPS-treated rats, ß1 and ß3-AR mRNA expression was decreased and associated to a reduced ß1 and ß3-induced vasodilation. Conversely, albeit ß2-AR mRNA was unchanged, the maximal ß2-AR-induced vasodilation increased by 49% in aortas from LPS-treated rats compared to controls. This increase was not affected by endothelium removal but was abolished in the presence of a ß2-AR antagonist or an adenylate cyclase inhibitor. CONCLUSIONS: In endotoxemia, ß2-AR vasodilation was increased by a potential recruitment of ß2-AR located on smooth muscle cells. This study suggests that vascular ß2-AR should be a putative new therapeutic target in septic shock.

[Epidemiology of cerebral perioperative vascular accidents]. / Épidémiologie des accidents vasculaires cérébraux périopératoires.

OBJECTIVES: Stroke is a well-described postoperative complication, after carotid and cardiac surgery. On the contrary, few studies are available concerning postoperative stroke in general non-cardiac non-carotid surgery. The high morbid-mortality of stroke justifies an extended analysis of recent literature. ARTICLE TYPE: Systematic review. DATA SOURCES: Firstly, Medline and Ovid databases using combination of stroke, cardiac surgery, carotid surgery, general non-cardiac non-carotid surgery as keywords; secondly, national and European epidemiologic databases; thirdly, expert and French health agency recommendations; lastly, reference book chapters. RESULTS: In cardiac surgery, with an incidence varying from 1.2 to 10% according to procedure complexity, stroke occurs peroperatively in 50% of cases and during the first 48 postoperative hours for the others. The incidence of stroke after carotid surgery is 1 to 20% according to the technique used as well as operator skills. Postoperative stroke is a rare (0.15% as mean, extremes around 0.02 to 1%) complication in general surgery, it occurs generally after the 24-48th postoperative hours, exceptional peroperatively, and 40% of them occurring in the first postoperative week. It concerned mainly aged patient in high-risk surgeries (hip fracture, vascular surgery). Postoperative stroke was associated to an increase in perioperative mortality in comparison to non-postoperative stroke operated patients. CONCLUSION: Postoperative stroke is a quality marker of the surgical teams' skill and has specific onset time and induces an increase of postoperative mortality.

[Argatroban, a new antithrombotic treatment for heparin-induced thrombocytopenia application in cardiac surgery and in intensive care]. / L'argatroban, nouvel antithrombotique pour la thrombopénie induite par l'héparine en chirurgie cardiaque de l'adulte: utilisation en chirurgie cardiaque et en réanimation.

OBJECTIVES: Although heparin-induced thrombocytopemia (HIT) is uncommon, its thromboembolic complications are potentially life-threatening. The low-molecular weight heparins are less responsible of HIT than unfractionated heparin (UFH) but this latter is still indicated in some circumstances such as cardiac surgery. Argatroban, a selective thrombin inhibitor, recently available, has been indicated in HIT treatment. This review presents the main pharmacological characteristics, its indications and uses in the context of cardiac surgery and in intensive care medicine. METHODS: Review of the literature in Medline database over the past 15 years using the following keywords: argatroban, cardiac surgery, circulatory assistance, cardiopulmonary bypass. RESULTS: Despite its short-acting pharmacokinetic, argatroban cannot be recommended during cardiopulmonary bypass. On the contrary, argatroban is indicated in many circumstances in postoperative period of various cardiac surgeries (on-pump, off-pump, circulatory assistance). Nevertheless, after cardiac surgery, doses have to be adapted according to coagulation laboratory testing (ACT), particularly in patients presenting acute organ failure (kidney injury, heart failure, liver failure). This compound has no antagonist and is excluded during severe hepatic failure. The continuous intravenous administration is a drawback. CONCLUSION: Argatroban is a new direct competitive thrombin inhibitor well evaluated as treatment of HIT after cardiac surgery. In HIT management, argatroban is an interesting alternative to lepirudin that is not anymore available and danaparoid because of supply disturbances.

Risk factors and pathogens involved in early ventilator-acquired pneumonia in patients with severe subarachnoid hemorrhage.

Ventilator-acquired pneumonia (VAP) is a common burden in intensive care unit (ICU) patients, but, to date, specific data are not available in patients with severe aneurysmal subarachnoid hemorrhage (SAH). A single neuro-ICU retrospective analysis of 193 patients with SAH requiring mechanical ventilation (MV) ≥48 h admitted from January 2005 to May 2010 was undertaken. The diagnosis of early VAP was prospectively upheld during a multidisciplinary staff meeting, according to the American Thoracic Society (ATS) 2005 guidelines with a threshold of 7 days after the onset of MV. Patients had a median age of 53 (44-62) years and 70 (36 %) were male. The median Glasgow coma scale (GCS) score before MV was 9 (5-14). 142 (74 %) patients had a World Federation of Neurosurgeons (WFNS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 162 (84 %) patients. 81 (48.7 %) patients declared an early VAP. On multivariate analysis, male sex (odds ratio [OR] 2.26, 95 % confidence interval [CI] [1.14-4.46]), use of mannitol before day 7 (OR 3.03, 95 % CI [1.54-5.95]), and achieving enteral nutrition ≥20 kcal kg(-1) day(-1) after day 7 (OR 2.91, 95 % CI [1.27-6.67]) remained independent risk factors of VAP. The main pathogens involved were methicillin-susceptible Staphylococcus aureus (MSSA) (34.9 %), Haemophilus influenzae (28.1 %), Streptococcus pneumoniae (15.5 %), and Enterobacteriaceae (10.7 %). Early VAP was associated with a longer duration of MV and ICU stay, but not with an excess of mortality. Early VAP bears significant morbidity in patients with severe SAH. Pathogens involved in early VAP are susceptible to antibiotics. Among modifiable risk factors of VAP, early enteral nutrition could be an easy and effective target.

Propofol versus thiopental by target controlled infusion in patients undergoing craniotomy.

BACKGROUND: For decades thiopental has been considered as the hypnotic drug of choice for intracranial surgery. However, total intravenous anesthesia performed with thiopental is associated with delayed recovery, whereas early post-operative neurological evaluation is critical. For this reason, target controlled infusion (TCI) of propofol is increasingly used for maintenance of anesthesia. However, a thiopental TCI has never been assessed for this purpose. We tested the hypothesis that a thiopental TCI provides an acceptable way to achieve early recovery compared to a propofol TCI during supratentorial surgery. METHODS: Eighty patients undergoing elective craniotomy for a supratentorial tumor were randomized to receive either a propofol TCI (group P) or a thiopental TCI (group T). Both groups received a sufentanil TCI and the bispectral index was monitored. The primary end-point was time to tracheal extubation. Secondary end-points were per- and post-operative hemodynamics as well as respiratory and recovery parameters. Assessment of study end-points was performed by an intensive care specialist blinded (like the patient) to the received hypnotic. RESULTS: Time to extubation was significantly (P<0.0001) shorter in group P (median 149 minutes; interquartile range 72-250 minutes) than in group T (median 453 minutes; interquartile range 286-813 minutes). Similarly, the recovery parameters were significantly better in group P than in group T. There was no difference between groups in terms of patient characteristics and hemodynamic parameters. CONCLUSION: Even with TCI and bispectral index monitoring, thiopental is associated with an inappropriate delayed recovery from supratentorial surgery compared to propofol TCI.

Ammonia plasma concentration and prolonged infusion of remifentanil in patients with acute kidney injury.

BACKGROUND: Glycine is an excipient of remifentanil and may induce side effects. To investigate glycine and ammonia concentration with the use of remifentanil in Intensive Care Unit patients with acute kidney injury (AKI) defined by a decrease in creatinine clearance above 50%. METHODS: Prospective open-label cohort study in three surgical Intensive Care Units. Thirty-three patients with AKI and requiring sedation for at least 72 hours. Sedation with remifentanil and midazolam or propofol was adapted every six hours according to ATICE. Glycine and ammonia plasma concentrations were measured at H0 (start of infusion) and every 12 hours during a continuous intravenous 72 hours remifentanil infusion, and 24 hours after the end of the infusion. Clinical and biological glycine or ammonia toxicity were evaluated. RESULTS: Fifteen patients required continuous veno-venous hemodiafiltration (CVVHDF). Glycine and ammonia plasma concentrations exceeded the normal value respectively for 11 (33%) and 15 (45%) patients before remifentanil infusion (H0). Accumulation of glycine or ammonia was observed neither for patients with or without CVVHDF. For patients without CVVHDF, the plasma ammonia concentration at the end of remifentanil infusion was significantly correlated with the creatinine clearance at H72 (P=0.03) and with the mean rate of remifentanil infusion (P=0.002). No side effect was reported. CONCLUSION: Remifentanil was not associated with an accumulation of glycine or ammonia in patients with AKI. Plasma ammonia concentration was correlated with the mean rate of remifentanil and creatinine clearance. A 72-hours remifentanil infusion appeared safe for sedation of patients with AKI.

[Perioperative adverse events related to antidepressive agents use]. / Complications liées à l'utilisation périopératoire des médicaments antidépresseurs.

OBJECTIVE: Depression is the most common psychiatric disease, which is treated by the use of antidepressive agents possessing various mechanisms of action. Thus, the use in preoperative period of antidepressive agents is frequent (7% of patients scheduled for surgery). The objective of this review was to update the knowledge on the drug interactions between antidepressive agents and drugs used in perioperative period. METHODS: (i) Medline and Ovid databases using combination of antidepressive agent and perioperative period as keywords; (ii) national and European epidemiologic database; (iii) expert recommendation and official French health agency; (iv) reference book chapters. RESULTS: The clinical practice showed a limited risk of adverse event related to antidepressant agents interaction with perioperative used drugs. In the two past decades, few relevant observations of adverse event related with imipramine and monoamine oxidase inhibitors use was reported. The most recent antidepressive agents had no serious adverse interaction. Nevertheless, the serotonin syndrome has to be known as far as it is more and more reported. In case of hypotension, the use of vasopressive agent has to be careful because of excessive response.

Investigation of the different adrenoceptor targets of nebivolol enantiomers in rat thoracic aorta.

BACKGROUND AND PURPOSE: Nebivolol is a highly selective beta(1)-adrenoceptor antagonist with beta(3)-adrenoceptor agonist properties and is a racemate mixture of D- and L-enantiomers. However, the cellular mechanisms of the effects of each enantiomer are not yet clear and are a matter for debate. The aim of the present experiments was to determine the adrenoceptors involved in the vascular effects of D- and L-enantiomers of nebivolol in rat thoracic aorta. EXPERIMENTAL APPROACH: Responses to nebivolol enantiomers were evaluated in rings of thoracic aorta from male Sprague-Dawley rats. KEY RESULTS: D-nebivolol (0.1-10 micromol.L(-1)), but not L-nebivolol, significantly shifted to the right the concentration-response curve to phenylephrine, an alpha(1)-adrenoceptor agonist, in a concentration-dependent manner. For the following experiments, aortic rings were constricted with endothelin 1 and now both enantiomers produced an endothelium-dependent relaxation of the rings involving the nitric oxide pathway. This relaxation was not modified by 1 micromol.L(-1) CGP 20,712A (beta(1)-adrenoceptor antagonist), but significantly blunted by 7 micromol.L(-1) L-74,8337 (beta(3)-adrenoceptor antagonist). However, only the vasorelaxation induced by D-nebivolol was significantly reduced by 1 micromol.L(-1) ICI 118,551 (beta(2)-adrenoceptor antagonist). CONCLUSIONS AND IMPLICATIONS: Our results suggest that the nebivolol enantiomers act on different targets. D-nebivolol induced vasorelaxation by activating beta(2)- and beta(3)-adrenoceptors and antagonizing alpha(1)-adrenoceptors. L-nebivolol induced vasorelaxation by activating only beta(3)-adrenoceptors in our model. Our results emphasize that nebivolol is a beta(1)-adrenoceptor antagonist with several important pharmacological differences from other beta(1)-adrenoceptor antagonists.

Sepsis is associated with an upregulation of functional beta3 adrenoceptors in the myocardium.

OBJECTIVE: To analyze the implication of the beta3-adrenoceptor (beta3-AR) pathway in human septic myocardium and a murine model of sepsis, a condition associated with myocardial depression. METHODS AND RESULTS: beta3-AR and eNOS protein abundance were increased (332+/-66.4% and 218+/-39.3; P<0.05) in hearts from septic patients. The effect of BRL37344, a beta3-AR-preferential agonist, was analyzed by videomicroscopy on the contractility of neonatal mouse ventricular myocytes (NMVM) incubated with conditioned medium from LPS-stimulated cultured macrophages (Mc-LPS+ medium). Stimulation of untreated NMVM with BRL37344 dose-dependently decreased the amplitude of contractile shortening (P<0.05). This response was abolished by L-NAME (NOS inhibitor). Incubation in Mc-LPS+ medium potentiated the depressing effect of BRL37344 (P<0.05) as well as of SR58611A (P<0.05) in wild-type myocytes. Importantly, the contractile depression was abrogated in cardiomyocytes from beta3-AR KO mice. CONCLUSIONS: beta3-AR are upregulated during sepsis in the human myocardium and by cytokines in murine cardiomyocytes, where they mediate an increased negative inotropic response to beta3 agonists. Activation of the beta3-AR pathway by catecholamines may contribute to the myocardial dysfunction in sepsis.

[Intra-aortic balloon pumping and heparin-induced thrombocytopenia]. / Contre-pulsion par ballonnet intra-aortique et thrombopénie induite par l'héparine non fractionnée.

Thrombocytopenia is frequently reported in the presence of intra-aortic balloon pumping (IABP) after cardiac surgery and in cardiology, but heparin-induced thrombocytopenia (HIT) is rarely responsible of it in this circumstance. A case-report if HIT in a patient with IABP is presented. This case emphasised the difficulty in diagnosis of HIT in this situation. An acute decrease in platelet count lasting after removal of IABP could suggest the diagnosis of HIT when other origins for thrombocytopenia are excluded.

[Use of heparin and platelet GPIIbIIIa inhibitor tirofiban for cardiac surgery in patients for suspicion of heparin-induced thrombocytopenia]. / Chirurgie cardiaque effectuée avec une association héparine non fractionnée et inhibiteur des récepteurs GPIIbIIIa plaquettaire (tirofiban) pour suspicion de TIH.

In a patient with heparin-induced thrombocytopenia few antithrombotic alternate treatments are proposed for cardiac surgery with or without cardiopulmonary bypass: danaparoid, lepirudine or powerful antiplatelet agent. Recently, the platelet GPIIbIIIa antagonist tirofiban (Aggrastat) was tested in humans. We reported two cases of patients operated upon for cardiac surgery with unfractionnated heparin (UFH) and tirofiban. The first patient underwent an off-pump coronary artery bypass graft and the second one a mitral valvular replacement under cardiopulmonary bypass. Tirofiban was associated with UFH and aprotinine. Postoperative bleeding was in the normal range for the two types of surgeries and haemodynamic tolerance was good. These two case reports support the possibility of secure cardiac surgery under efficient platelet inhibition with tirofiban. The management of cardiac surgery with tirofiban without monitoring of platelet aggregation appeared to be more simple than with the other alternate antithrombotic agents.

[Value of epidural blood-patches for the treatment of spontaneous intracranial hypotension]. / Intérêt du blood-patch pour le traitement de l'hypotension intracrânienne spontanée.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) is a rare syndrome. It is due most often to a spinal meningeal leak. Symptoms due to SIH are often difficult to treat and epidural blood-patch (BP) has been proposed. The aim was to evaluate the effects and the problems associated with lumbar blood-patch to treat SIH. STUDY DESIGN: Case series. PATIENTS AND METHODS: The diagnosis of SIH was made in six consecutive patients on clinical signs and radiological findings (CT-scan and MRI). A lumbar BP (L1-L2 level) was performed as soon as possible after diagnosis. A maximum of three procedures was allowed in case of failure of the initial BP. RESULTS: BP was effective and well tolerated for five patients (3 immediately after BP, 2 others patients needed 2 and 3 BP). In one patient, an incomplete response was observed and was related to a large CFS leak diagnosed by CT-myelogram. CONCLUSION: When the diagnosis of spontaneous intracranial hypotension is confirmed, a repeated blood patch lumbar procedure can be efficient to treat these patients.

Place of beta 3-adrenoceptors among other beta-adrenoceptor subtypes in the regulation of the cardiovascular system.

Knowledge of the sympathetic system is a basic element in the understanding of numerous physiological and physiopathological phenomena. In the two last decades, new pharmacological, biochemical and molecular tools have changed our approach to the roles of beta-adrenoceptors in the cardiovascular system. In the heart, the positive inotropic effect of predominant beta 1-adrenoceptor stimulation is classically recognised. Several studies reveal a significant physiological relevance of the beta 2-adrenoceptor which could activate different signalling pathways in addition to that of cAMP. Moreover, the detection of a third beta-adrenoceptor subtype, beta 3, in human heart, responsible for a negative inotropic effect through a NO signalling pathway, has changed the classically admitted paradigm on the regulation of heart function by the beta-adrenergic system. The identification of atypical beta-adrenoceptors, based on pharmacological tools, led to the discovery of "putative" beta 4-adrenoceptors, which constituted a low affinity state of the beta 1-adrenoceptors. In vessels, all beta-adrenoceptors subtypes, beta 1, beta 2 and beta 3, mediated a vasodilation, but the signalling pathway involved in this effect was variable according to their localization (endothelial or smooth muscle cells), the species and the vascular bed. beta-adrenoceptors are involved in several cardiovascular disease and could constitute a determinant therapeutic target. The efficiency of some beta-blockers used in the treatment of heart failure could result from action on beta 3-adrenoceptors. Moreover, a mutation of the beta-adrenoceptor subtype suggested a role in hypertension and diabetes mellitus.

[Effects of plasma substitutes on hemostasis]. / Effets des solutés de remplissage vasculaire sur l'hémostase.

OBJECTIVE: Data synthesis on haemostasis effects of cristalloids and colloids and clinical implications for their use for plasma volume replacement. DATA SOURCES: Data were searched in the Medline database from 1954 to 2000 using the following key-words: cristalloids, colloids, albumin, gelatin, dextran, hydroxyethyl starch, haemostasis, von Willebrand disease, haemodilution. DATA EXTRACTION: Publications from 1954 to 1990 were selected depending on the quality of their methodology. Most of articles published after 1990 and all types including case report were accepted. DATA SYNTHESIS: Cristalloids induces a moderate hypercoagulable state with 10 to 30% haemodilution. Hypocoagulation is observed above 50% haemodilution. Albumin does not impair hemostasis except with a 50% or more haemodilution where hypocoagulation is observed. Dextran dramatically impairs haemostasis and fibrinolysis. With increasing dose, a progressive decrease of all von Willebrand multimers, mostly the largest, is observed. Till 50% haemodilution, gelatin has a moderate impact on hemostasis, but platelet aggregation is moderately modified. However this moderate impairment of haemostasis may potentiate the haemostatic effect of other colloids when used in association with gelatin. More than 30% haemodilution with hydroxyethyl starch (HES) has a serious effect in vitro on platelet function and fibrinoformation. In most studies in human, less than 20 ml.kg-1 plasma volume replacement has no clinical impact, but in some evaluations postoperative bleeding is more important with HES, particularly HES 450, in comparison to other colloids. With HES 450 and HES 200 highly substituted (0.6 of degree of substitution) intravascular cumulation of large molecules leads to type I von Willebrand syndrome when doses overtake 80 ml.kg-1. Dextran and HES are prohibited in patients with impaired haemostasis due to congenital disease (haemophilia and von Willebrand disease) or acquired defect (thrombocytopenia). Caution is required in patients with renal failure or receiving antithrombotic or non-steroidal anti-inflammatory agents. Patients without a haemorrhagic diathesis must not received more than 1.5 g.kg-1.j-1 of dextran and restrictive conditions of use must be respected with HES. CONCLUSION: Except isotonic cristalloids, all colloids induce haemostastic changes particularly for haemodilution over 30%. Effects are more pronounced with HES and dextran.

[Post-traumatic hematoma of the esophagus]. / Hématome post-traumatique de l'oesophage.

A 20-year-old man was admitted after a traffic accident for a closed chest trauma. Initial evaluation showed a sternal fracture with a minor pneumomediastinum. Twenty-four hours later be experienced an acute respiratory failure, due to total left pulmonary atelectasis from indirect compression of the left main stem bronchus. Mediastinal widening at the postero-superior level was visualized by CT scan. The aortogram was normal. Thoracotomy showed a moderate left haemothorax, associated with an intramural haematoma of the low thoracic oesophagus which was respected. The time course was uneventful, except repetitive atelectases treated by fibrescopic aspiration. Oesophageal haematoma secondary to chest trauma is a rare injury, with around 10 cases reported in the literature. Compression of tracheobronchial axis is exceptional. Because of the delayed occurrence of such a complication after chest trauma, with sternal fracture, close clinical surveillance and CT scans are essential.