Correction to: "in-vitro examination of the positive inotropic effect of caffeine and taurine, the two most frequent active ingredients of energy drinks".

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In-vitro examination of the positive inotropic effect of caffeine and taurine, the two most frequent active ingredients of energy drinks.

BACKGROUND: Our study aimed to evaluate changes in the contractile behavior of human myocardium after exposure to caffeine and taurine, the main active ingredients of energy drinks (EDs), and to evaluate whether taurine exhibits any inotropic effect at all in the dosages commonly used in EDs. METHODS: Myocardial tissue was removed from the right atrial appendages of patients undergoing cardiac surgery and prepared to obtain specimens measuring 4 mm in length. A total of 92 specimens were exposed to electrical impulses at a frequency of 75 bpm for at least 40 min to elicit their maximum contractile force before measuring the isometric contractile force (ICF) and duration of contraction (CD). Following this, each specimen was treated with either taurine (group 1, n = 29), or caffeine (group 2, n = 31) or both (group 3, n = 32). After exposure, ICF and CD measuring were repeated. Post-treatment values were compared with pre-treatments values and indicated as percentages. RESULTS: Exposure to taurine did not alter the contraction behavior of the specimens. Exposure to caffeine, in contrast, led to a significant increase in ICF (118 ± 03%, p < 0.01) und a marginal decrease in CD (95 ± 1.6%, p < 0.01). Exposure to a combination of caffeine and taurine also induced a statistically significant increase in ICF (124 ± 4%, p < 0.01) and a subtle reduction in CD (92 ± 1.4%, p < 0.01). The increase in ICF achieved by administration of caffeine was similar to that achieved by a combination of both caffeine and taurine (p = 0.2). The relative ICF levels achieved by administration of caffeine and a combination of taurine and caffeine, respectively, were both significantly higher (p < 0.01) than the ICF resulting from exposure to taurine only. CONCLUSION: While caffeine altered the contraction behavior of the specimen significantly in our in-vitro model, taurine did not exhibit a significant effect. Adding taurine to caffeine did not significantly enhance or reduce the effect of caffeine.

Ultrastructure of pheochromocytoma: undescribed morphologic features.

We examined samples of human pheochromocytoma from 11 patients aged 30-70 years including one case of malignant pheochromocytoma with a view to identifying previously unreported ultrastructural details.We identified two types of nuclear inclusions consisting of irregularly shaped singular or multiple granulofibrillar formations with a typical concentric halo, on the one hand, and accumulations of egg-shaped structures consisting of granules and microfilaments, on the other. In some of the tumor cells, membrane-covered inclusions containing parallel laminar elements arranged in a paracrystalline, periodic fashion, or mega-mitrochondriae characterized by increased electrodensity of their matrix, and fibrillary material in the spaces between the cristae were present. A frequent finding consisted of typical ciliary formations, while rough/smooth tubular aggregates of different size occurred less frequently. Finally, we were able to demonstrate the uptake of norepinephrine by smooth muscle fibers in the periphery of arterial vessels as evidenced by linear accumulations of membrane-covered granules separating bands of contractile smooth muscle components in the peripheral layers of arterial vessels close to norepinephrine producing neoplastic cells.These findings represent ultrastructural features that contribute to further elucidating the ultrastructural characteristics of the human pheochromocytoma.

Daptomycin for the treatment of major gram-positive infections after cardiac surgery.

BACKGROUND: Infection is a main cause of morbidity and mortality after heart surgery, with multi-resistant pathogens increasingly representing a challenge. Daptomycin provides bactericidal activity against gram-positive organisms that are resistant to standard treatment including vancomycin. METHODS: A cohort of cardiac surgical patients, treated with daptomycin for major infection at two tertiary care centers, were retrospectively studied with a particular focus on the type of infection, causative pathogens and co-infections, daptomycin dosage, adverse events and outcome in order to provide evidence for the efficiency and safety of daptomycin in a distinct high-risk patient population. RESULTS: Sixty-five patients (87.7 % males, 60.4 ± 13.5 years) who had undergone aortic surgery (20.0 %), ventricular assist device (VAD) implantation (21.5 %), combined procedures (21.5 %), coronary artery bypass grafting (12.3 %), isolated valve surgery (15.4 %) and heart transplantation (7.7 %) were diagnosed with catheter-related infection (26.1 %), valve endocarditis (18.8 %), sternal wound (13.0 %), VAD-associated (11.6 %), cardiac implantable electrophysiological device (CIED)-associated (4.1 %), respiratory tract (4.3 %), bloodstream (4.3 %) and other infection (4.3 %). In 13.0 %, no focus of infection was identified though symptoms of severe infection were present. The most frequent pathogens were Staphylococcus epidermidis (30.4 %), Staphylococcus aureus (23.1 %) and Enterococcus species (10.1 %). Daptomycin doses ranging from 3 mg/kg every 48 h to 10 mg/kg every 24 h were administered for 15.4 ± 11.8 days. 87.0 % of the cases were classified as success, 7.2 % as treatment failure and 5.8 as non-evaluable. Adverse events were limited to one case of mild and one case of moderate neutropenia with recovery upon termination of treatment. CONCLUSION: Daptomycin proved safe and effective in major infection in high-risk cardiac surgical patients.

Left ventricular non-compaction cardiomyopathy and left ventricular assist device: a word of caution.

BACKGROUND: In patients with left ventricular non-compaction (LVNC), implantation of a left ventricular assist device (LVAD) may be performed as a bridge to transplantation. In this respect, the particular characteristics of the left ventricular myocardium may represent a challenge. CASE PRESENTATION: We report a patient with LVNC who required urgent heart transplantation for inflow cannula obstruction nine months after receiving a LVAD. LVAD parameters, echocardiography and examination of the explanted heart suggested changes of left ventricular configuration brought about by LVAD support as the most likely cause of inflow cannula obstruction. CONCLUSIONS: We conclude that changes experienced by non-compacted myocardium during LVAD support may give rise to inflow cannula obstruction and flow reduction. Presence of LVNC mandates tight surveillance for changes in LV configuration and LVAD flow characteristics and may justify urgent transplantation listing status.

Postoperative Heparin-Mediated Extracorporeal Low-Density Lipoprotein Fibrinogen Precipitation Aphaeresis Prevents Early Graft Occlusion after Coronary Artery Bypass Grafting.

Background Early graft occlusion due to thromboembolic events is a well-known complication after coronary artery bypass grafting (CABG). Fibrinogen, the coagulation factor I, is a glycoprotein that is transformed by thrombin into fibrin. It plays a major role in thrombus formation and is highly elevated after CABG. Our aim was to determine if postoperative lowering of fibrinogen levels by H.E.L.P. (heparin-mediated extracorporeal low-density lipoprotein [LDL] fibrinogen precipitation) aphaeresis could reduce the rate of early graft occlusion in patients with hypercholesterolemia undergoing CABG. Methods Between December 2004 and September 2009, 36 male patients with hypercholesterolemia (mean LDL cholesterol 128 ± 12 mg/dL), mean age 58 ± 9 years, underwent CABG. Mean preoperative fibrinogen level was 387 ± 17 mg/dL. H.E.L.P. aphaeresis was postoperatively performed when fibrinogen levels exceeded 350 mg/dL on day 1 and 250 mg/dL every consecutive day up to day 8. Pre- and postaphaeresis blood samples were obtained and plasma fibrinogen level reduction was calculated. Early graft occlusion was evaluated by means of coronary angiography or multislice computed tomography before discharge. Results A total of 128 distal anastomoses were performed in 36 patients (mean 3.6/patient). Postoperatively, 191 H.E.L.P. aphaeresis sessions were performed (mean 5.3/patient). Fibrinogen levels were lowered from 391 ± 10 mg/dL (preaphaeresis) to 171 ± 5 mg/dL (postaphaeresis; p < 0.001). Coronary angiography (multislice computed tomography in 7 patients) revealed graft patency in 125 of 128 grafts (98% patency) with three occluded venous grafts to target vessels of 1.5 mm. H.E.L.P. aphaeresis-related complications were limited to hypotensive episodes in two patients and bacteremia in one patient. Conclusions H.E.L.P. apheresis offers an easy, save, and efficient method to decrease fibrinogen postoperatively in patients having CABG. Showing excellent graft patency rates in comparison to the literature, this method is a promising tool to reduce early graft occlusion after CABG.

Suspected involvement of EPTFE membrane in sterile intrathoracic abscess and pericardial empyema in a multi-allergic LVAD recipient: a case report.

Device-related infections in recipients of left ventricular assist devices (LVAD) have been recognized as a major source of morbidity and mortality. They require a high level of diagnostic effort as part of the overall burden resulting from infectious complications in LVAD recipients. We present a multi-allergic patient who was treated for persistent sterile intrathoracic abscess formation and pericardial empyema following minimally invasive LVAD implantation including use of a sheet of e-polytetrafluoroethylene (ePTFE) membrane to restore pericardial integrity. Sterile abscess formation and pericardial empyema recurred after surgical removal until the ePTFE membrane was removed, suggesting that in disposed patients, ePTFE may be related to sterile abscess formation or sterile empyema.

Necrotizing pulmonary aspergillosis and ventricular assist device infection: case report and review of literature.

Necrotizing pulmonary aspergillosis and Aspergillus device infection are rare and have potentially fatal complications after left ventricular assist device (LVAD) implantation. To date, few cases of patients surviving Aspergillus device infection have been published, with survival reported only after device removal. We present a patient implanted with an LVAD in whom necrotizing pulmonary aspergillosis with device involvement was successfully treated by segmentectomy and prolonged antifungal treatment without device exchange or removal. Similar cases in the literature were searched for and are discussed in view of the severity of this complication.

Dose/time-dependent modulation of the endothelial function through induction agents: non-depleting versus depleting agents.

BACKGROUND: Polyclonal anti-thymocyte globulins (ATGs) and anti-CD25 antibodies are agents used for induction of immunosuppression in solid-organ transplantation. We aimed to investigate the effect of different regimens of these immunosuppressive induction agents on transendothelial migration of peripheral blood mononuclear cells (PBMC) and evaluated the endothelial apoptosis after treatment. METHODS: Human microvascular endothelial cells were either activated with tumor necrosis factor-α/interferon-γ or not and further treated with 25 or 125 µg/mL ATG (Thymoglobulin, Sanofi-Aventis, Germany) for 2 hours or 24 hours, or with 5 µg/mL Basiliximab (Simulect, Novartis, Germany) for 2 hours or 24 hours. PBMC were either activated with phytohaemagglutinin (PHA) or not and further treated with 25 or 125 µg/mL ATG or with 5 µg/mL Basiliximab for 2 h and then used for transendothelial migration assays. Apoptosis of endothelial cells was detected by means of Annexin-V staining after 2-hour incubation with either 25 or 125 µg/mL ATG or 5 µg/mL Basiliximab. RESULTS: Prophylactic 24-hour administration of ATG to naive endothelial cells without PBMC treatment reduced transendothelial migration. Prophylactic 24-hour administration of ATG and Basiliximab to naive endothelial cells after PBMC treatment with the same agents reduced the transendothelial migration after 24 hours. In both cases, no effect could be observed after 2-hour treatment. Basiliximab but not ATG showed a reduction of transmigration after 2-hour treatment of PBMCs without naive EC treatment. Apoptosis of endothelial cells after treatment increased in both cases, being in case of ATG dose-dependent, increasing from 1.2% after either 25 µg/mL ATG to 8.7% after 125 µg/mL ATG. CONCLUSIONS: Immunosuppressive induction agents modulate the endothelial activity in a dose- and time-dependent manner. Our results suggest that administration of induction agents over longer time periods could provide a potential benefit regarding endothelial immunomodulation. Increased doses may, however, show a deleterious effect on endothelial survival.

ATG-Fresenius inhibits blood circulating cell proliferation in a dose-dependent manner: an experimental study.

INTRODUCTION: Antithymocyte globulin (ATG)-Fresenius (Neovii-Biotech, Graefelfing, Germany), a highly purified rabbit polyclonal antihuman T-lymphocyte immunoglobulin resulting from immunization of rabbits with the Jurkat T-lymphoblast cell line, is currently used for the prevention of acute rejection in patients receiving solid organ transplants. Our aim was to investigate the in vitro activity of ATG-Fresenius regarding the proliferation of peripheral blood mononuclear cells (PBMCs), an important mechanism of rejection after solid organ transplantation. METHODS: PBMCs were isolated from 6 healthy donors. Proliferation was assayed using [(3)H] thymidine incorporation. For analysis of mitogen-stimulated proliferation, the PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius in the absence/presence of 40 µg/mL phytohemagglutinin. For analysis of the mixed lymphocyte reaction, PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius for 3 days. On day 3, PBMCs (stimulator cells) from allogeneic donors were incubated with 25 µg/mL mitomycin C. The responder cells (preincubated with ATG-Fresenius) were then cultured at 37°C with the stimulator cells for 6 days. Groups were compared using ANOVA and the Tukey-Kramer multiple comparison test. RESULTS: Preincubation of PBMCs with ATG results in concentration-dependent inhibition of phytohemagglutinin-stimulated proliferation. The effect was more pronounced after 2 and 3 days of treatment with ATG compared with 1 day. There was a concentration-dependent decrease in the mixed lymphocyte reaction-induced proliferation (up to 80%) at ATG-Fresenius concentrations as low as 0.05 to 0.5 µg/mL. No further effect on proliferation at ATG-Fresenius concentrations of 0.5 to 50 µg/mL was seen, and higher concentrations (>100 µg/mL) totally inhibited proliferation. CONCLUSIONS: Our in vitro results provide more evidence of the beneficial effect of ATGs in the early phase of solid organ transplantation, by reducing effector cell proliferation.

In vitro effects of ATG-Fresenius on immune cell adhesion.

INTRODUCTION: ATG-Fresenius, a purified rabbit polyclonal anti-human T-lymphocyte immunoglobulin is used for induction immunosuppression as well as prevention and treatment of acute rejection episodes among patients receiving solid organ transplants. The aim of this study was to investigate the in vitro activity of ATG-Fresenius upon immune cell adhesion, which may explain its activity to mitigate ischemia-reperfusion injury. MATERIALS AND METHODS: Human vascular endothelial cells (HUVEC) and peripheral blood mononuclear cells (PBMCs) isolated from umbilical vein or peripheral blood were incubated 20 to 24 hours before analysis. HUVEC were incubated with 10 and 100 µg/mL ATG-Fresenius or reference polyclonal rabbit immunoglobulin G. Analysis of immune cell adhesion to endothelial cells was studied in cocultures of PBMCs and adherent HUVEC. Endothelial cell expression of adhesion molecules CD62E and CD54 was determined by flow cytometry. The numbers of T-, B- and natural killer cells attached to HUVEC were also determined by flow cytometry. Groups were compared using one-way analysis of variance. RESULTS: We showed that ATG-Fresenius binds to endothelial cells particularly activated ones expressing increased levels of E-selectin and ICAM-1. The increased binding of ATG-Fresenius to activated endothelial cells was consistent with its known binding to Intercellular Adhesion Molecule 1 (ICAM-1) and selectins. We also showed that ATG-Fresenius inhibited adhesion of prestimulated immune cells to activated endothelium. CONCLUSION: We demonstrated dose-dependent binding of ATG-Fresenius to activated endothelial cells.

Platelet factor 4-positive thrombi adhering to the ventricles of a ventricular assist device in patients with heparin-induced thrombocytopenia type II.

BACKGROUND: Thromboembolism is a major complication in patients with ventricular assist devices (VADs). Drug anticoagulation and the use of biocompatible surfaces, such as coating with heparin, aim to reduce thromboembolism in these patients. Administration of heparin can lead to heparin-induced thrombocytopenia (HIT) type II, mainly through heparin/platelet factor 4 (PF4) antibodies. We assessed the presence of PF4 antibodies in VAD thrombi of patients with heparin-coated VADs and HIT II. METHODS: Thrombi (n = 6) were obtained from the replaced Excor ventricles of patients with HIT II after biventricular VAD implantation (Excor Adult; Berlin Heart, Germany). Excor ventricles were changed after clinical examination and suspicion of thrombi in the polyurethane valves. Expression of PF4- antibodies was assessed with the use of a polyclonal rabbit antibody (anti-PF4 antibody; Abcam, USA). Expression was assessed by 2 independent observers. RESULTS: Biopsies of all thrombi showed an extreme positive immunoreaction for PF4. No differences between the different thrombi and localization (left/right Excor ventricle) were observed. The thrombi were organized, without lamination of fibrin and cellular layers. CONCLUSIONS: Platelet surface expression of PF4 in the thrombi reflects HIT antigen presentation. The physical relationship between the PF4-positive thrombi and the heparin-coated surface suggests that onset of HIT II could be influenced by the immobilized heparin coating.

[Daptomycin for the treatment of gram-positive infections after cardiac surgery]. / Daptomycin zur Behandlung grampositiver Infektionen nach herzchirurgischen Eingriffen.

BACKGROUND AND METHOD: Surgical infection remains a main cause of death after heart surgery, despite advances in pharmacological therapy. Daptomycin is a cyclic lipopeptide antibiotic, useful in gram-positive organisms resistant to standard treatment, including vancomycin. The aim of this study was to describe the use of daptomycin regarding efficacy, efficiency and safety in patients with gram-positive infections after heart surgery using a retrospective analysis on 49 adult patients. CONCLUSION: Daptomycin shows excellent in vitro and in vivo activity against gram-positive organisms, such as Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, especially MRSA. Daptomycin is also effective against increasing vancomycin-resistant or vancomycin-intermediate S. aureus.

Pre-filling of the extracorporeal circuit with autologous blood is safe, but not effective in optimizing biocompatibility in high-risk patients.

OBJECTIVES: Haemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusions in high-risk cardiac surgery patients. We designed this study to evaluate the effects of antegrade autologous priming (AAP) on reducing perioperative blood transfusion and markers of the inflammatory response in older patients (>75 years). METHODS: Seventy-two patients undergoing first-time coronary bypass and/or aortic valve replacement were prospectively randomised to a cardiopulmonary bypass (CPB) with or without AAP. AAP was performed by adding the patient's own blood to the prime solution (mean 280 ml). Perfusion and anaesthetic techniques were as usual. The haematocrit was maintained at a minimum of 21% during CPB. Patients were well matched for all preoperative variables, including established transfusion risk factors. The primary endpoint was the requirement of red cell transfusion. The surrogate endpoints were renal function, inflammatory response and ischaemic parameters. Blood samples were drawn pre- and intraoperatively and at intervals of 6 hours till POD 6. RESULTS: Current analysis shows no differences in patients receiving homologous packed red cell transfusions. Also, markers of the inflammatory response (IL6, IL8), renal function (cystatin C, creatinine) and myocardial ischaemia (troponin T, CK-MB) were comparable in both groups (p>0.05). Clinical outcomes were similar with respect to pulmonary, renal and hepatic function, length of ICU stay and hospital stay. CONCLUSION: These data suggest that antegrade autologous priming is a safe procedure, but an ineffective way for improving biocompatibility and reducing the need for blood transfusion in older patients.

Indocyanine green clearance after cardiac surgery: the impact of cardiopulmonary bypass.

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven.

Levosimendan for primary graft failure after heart transplantation: a 3-year follow-up.

BACKGROUND: Primary graft failure (PGF) is a severe complication responsible for 42% of the in-hospital mortality after heart transplantation. It has been postulated that once 30-day survival is achieved, patients with PGF have no increased risk of death. Levosimendan increases the 30-day survival among patients with PGF. Herein we have reported a 3-year follow-up at a single center of a patient cohort including PGF cases treated with levosimendan. METHODS: From September 2005 to December 2006 53 patients underwent heart transplantation at our institution, including 12 patients (22.6%) who presented with PGF and were treated with levosimendan using a 24-hour continuous infusion (0.10 µg/kg/min). Risk factors for 1-year and three-year mortality were analyzed using 30-day as well as 1 and 3-year survivals comparing patients with versus without PGF (n = 41). RESULTS: There were no significant differences in donor age, weight, height, and serum sodium between the groups. However, the ischemia time (259 ± 53 vs 227 ± 50 min; P = .06) and recipient age (51.6 ± 15 vs 41.5 ± 21 years; P = .07) were greater among the PGF patients. The 30-day survival rate was 92% in both groups. After 1 and 3 years, the survival rate was significantly lower among the PGF cohort (50% vs 80.6% and 41.7% vs 80.6%; P < .05) with 86.5% of PGF patients succunding due to non cardiac reasons, predominantly infections. CONCLUSIONS: Although treatment of PGF with levosimendan increased the 30-day survival, the 1 year and 3-year rates were reduced among this cohort of patients. PGF was associated with poor long-term outcomes, which may be a consequence of systemic malperfusion during the stage of cardiac low-output after transplantation.

Stress doses of hydrocortisone reduce systemic inflammatory response in patients undergoing cardiac surgery without cardiopulmonary bypass.

BACKGROUND: Systemic inflammatory response occurs after cardiac surgery (CS) and leads to a worse outcome in many cases. Stress doses of hydrocortisone have been successfully used to reduce SIRS and to improve outcome of patients after CS with cardiopulmonary bypass grafting (on-pump CABG), but the effect of hydrocortisone on patients undergoing CS without cardiopulmonary bypass grafting (off-pump CABG) is unclear. Therefore, we evaluated the effect of stress doses of hydrocortisone in this group of patients. METHODS: A total of 305 patients undergoing off-pump CABG were enrolled in a prospective randomized trial according to the study protocol. The patients either received stress doses of hydrocortisone or placebo. We measured various laboratory and clinical variables characterizing the patients' outcomes. RESULTS: The two study groups did not differ with regard to demographic data. Patients receiving hydrocortisone had an increased Higgins score and a decreased ejection fraction. Furthermore, patients from the hydrocortisone group had significantly lower levels of IL-6 (275 [162/677] pg/mL vs. 450 [320/660] pg/mL, P=0.001) and a shorter stay in the ICU (1 [1/3] day vs. 2 [2/3] days, P=0.04). Both groups did not differ in regard to catecholamine support, duration of mechanical ventilation, incidence of postoperative atrial fibrillation, blood loss, and mortality rate. CONCLUSION: We conclude that intravenous stress doses of hydrocortisone lead to a reduction of systemic inflammation and to a potential improvement in the early outcome of patients undergoing off-pump CABG.

Genetic polymorphisms of TP53 and FAS promoter modulate the progression of coronary artery disease after coronary artery bypass grafting: a gender-specific view.

INTRODUCTION: Progression of coronary artery disease (CAD) after primary coronary artery bypass grafting (CABG) is frequent and may lead to recurrent symptoms. Various data indicate that apoptosis is the main event occurring during development and progression of atherosclerotic plaque. Plaque vascular smooth muscle cells (VSMCs) are more sensitive than regular VSMCs to TP53-mediated apoptosis. METHODS: We investigated EDTA blood of 192 patients (18% female, age 60.9 ± 7.4 years) who had primary CABG more than 5 years ago. CAD progression was defined as clinical endpoints: re-operation (n = 88; 46%), catheter re-intervention (n = 58; 30%), or angina at follow-up (n = 89; 46%). Apoptotic gene polymorphisms (Toll-like receptor 2 A753G, FAS ligand C-844T, FAS promoter G-670A, TP53 Arg72Pro, and CD14 C-260T) were investigated by PCR-RFLP and compared to healthy controls (n = 200, 24% female, age 63.4 ± 5.4). Gender-specific analysis was carried out. RESULTS: Heterozygous, homozygous and wild-type expression of all five genetic polymorphisms showed almost identical distribution between patients with CAD and healthy controls. Looking at clinical endpoints, with GG expression of Toll-like receptor 2 polymorphism and GG expression of FAS promoter polymorphism, results showed a relative increased risk (p = 0.09) for recurrent symptoms and re-intervention. Patients with FAS promoter polymorphism with AA expression had an increased risk of suffering from recurrent symptoms (n = 28, p = 0.04). We found that patients with homozygous expression of TP53 polymorphisms (n = 3, all male) were prone to needing re-intervention after prior CABG (p = 0.03), but not re-operation. Over a period up to 15 years, the re-intervention rate was significantly different in homozygous genotypes of FAS LG, FAS promoter and TP53. CONCLUSIONS: Patients presenting with polymorphisms of FAS LG, FAS promoter and TP53 have an increased risk of CAD progression, as they have a higher rate of re-interventions.

Influence of polyclonal antithymocyte globulins on the expression of adhesion molecules of isolated human umbilical vein endothelial cells.

OBJECTIVES: Polyclonal antithymocyte globulins (ATGs) are immunosuppressive agents applied for the treatment and prevention of organ rejection after transplantation. ATGs induce complement-mediated cell death in T lymphocytes and decrease leukocyte adhesion. However, little is known about the effects of ATGs on endothelial cells (EC). Our aim was to study the influence of ATGs upon the expression of adhesion molecules on human umbilical vein endothelial cells (HUVECs) after stimulation with tumor necrosis factor (TNF)-alpha. MATERIAL AND METHODS: HUVECs obtained from umbilical cords were incubated with ATGs before and after 6-hour stimulation with TNF-alpha. The group incubated without ATG served as the controls. Another group was not stimulated with TNF-alpha. By flow cytometry, we analyzed the expression of several adhesion molecules: intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM), platelet EC adhesion molecule (PECAM), and CD62E. Statistical analysis used analysis of variance. RESULTS: After TNF-alpha stimulation, the EC surface expression of ICAM-1 and CD62E was reduced, although not significantly, in treated as compared with untreated cells. The expression of ICAM-1 and CD62E was similar in the unstimulated groups. The expression of VCAM, PECAM, CD55, and CD58 was not modified by ATG treatment. CONCLUSION: Our results demonstrated that ATGs insignificantly reduced the expression of adhesion molecules in HUVECs. The effect of ATGs on stimulated HUVECs remains unclear, probably due to the lack of effector cells.

Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery.

BACKGROUND: The endocannabinoid system (ECS) is an endogenous signalling system which includes the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and specific G-protein-coupled endocannabinoid receptors (CB1 and CB2). Recent studies have described important roles of the peripheral ECS in human atherosclerosis, cardiometabolic disorders, heart failure, and systemic inflammation. We sought to study changes in plasma endocannabinoid concentrations during cardiac surgery (CS) under general anaesthesia with isoflurane/sufentanil, and during cardiopulmonary bypass (CPB). METHODS: We studied 30 patients undergoing CS with CPB. All patients received midazolam and sufentanil for induction and isoflurane and sufentanil for maintenance of general anaesthesia. Blood samples were drawn before and after induction of general anaesthesia, after the beginning of surgery, during and after weaning from CPB, and after admission to intensive care unit (ICU) after surgery. Endocannabinoid measurements were performed by HPLC-tandem mass spectrometry. RESULTS: Induction of general anaesthesia led to a significant decline in plasma AEA concentrations [from mean (sd) 0.39 (0.03) to 0.27 (0.03) ng ml(-1), P<0.01]. CPB induced a pronounced increase in 2-AG concentrations [from 112.5 (163.5) to 321.0 (120.4) ng ml(-1), P<0.01], whereas AEA concentrations remained persistently low until admission to the ICU. 2-AG concentrations returned to preoperative values after surgery. CONCLUSIONS: General anaesthesia with isoflurane significantly reduces plasma AEA concentrations. This could be a consequence of stress reduction after loss of consciousness. The significant increase in 2-AG after initiation of CPB may be part of an inflammatory response. These findings suggest that anaesthesia and surgery have differential effects on the ECS which could have substantial clinical consequences.