Search

The outflux of chloride through the isolated skin ( J) of the South American frog Leptodactylus ocellatus (L.) is carried by a mechanism that saturates at high concentration of chloride on the inside, and is stimulated by the presence of Cl in the outer solution ( trans side). The presence of Na on the outside, by itself, does not increase J. However, when J is already increased by chloride on the trans side, the addition of Na produces a significant further increase. At low concentration of Cl on the outside J proceeds through a route which involves changes in electrical parameters. The results suggest that both mechanisms are located on the cell membranes and, therefore, that the fluxes would cross through the cytoplasm of the cells. Na stimulates the second mechanism only. [ABSTRACT FROM AUTHOR]

At low concentration (1 mm) of Cl in the outer solution, the influx of chloride through the isolated skin ( J) of the South American frog Leptodactylus ocellatus (L.) seems to be carried by two mechanisms: (i) a passive one that exhibits the characteristics of an exchange diffusion process, and (ii) an active penetration. Studies of the influx and efflux of chloride ( J and J) indicate, that the presence of a high (107 mm) concentration of Cl in the outer solution activates the translocation of this ion through the cells. Studies of the unidirectional flux of Cl across the outer barrier ( J) indicate that Na out stimulates the penetration of Cl at this level. Cl out, in turn, stimulates, the J, but this effect is only detected at low concentrations of Na out. [ABSTRACT FROM AUTHOR]

During their flux through the skin of the frog Leptodactylus ocellatus, Na and Cl interact with each other. This interaction gives rise to electrical phenomena which are studied in the present paper. The skin is mounted in NaSO Ringer's with 115 mM Na on the inside, and a variety of outer solutions,. The osmolarity of all solutions is kept constant at 237.8 mosmol by adding sucrose. When the main anion used on the outside is SO the electrical potential difference (Δψ) rises steadily with the concentration of sodium (Na) up to 87 mV, which is reached at about 20 mm. Thereafter Δψ remains constant. When the main anion is Cl it is observed that Δψ rises steadily with (NaCl) with a slope similar to the curve obtained with SO (37 mV per decade), but with a lower intercept attributed to an inward Cl pumping which is characteristic of this frog species. At 2-9 mM (NaCl) a Cl-specific channel is activated. Further increases of (NaCl) produce a decrease of Δψ. The specificity of the activation of this site by monovalent cations and its use by monovalent anions is also studied. [ABSTRACT FROM AUTHOR]

It is generally acknowledged that microplastic pollutants are prevalent in ocean waters and sediments across a range of tropical, temperate, subpolar, and polar regions. The waters surrounding King George Island are significantly impacted by human activities, particularly those related to scientific stations, fishing, and tourism. Organisms, such as Laternula elliptica, can be used as environmental monitors due to the likelihood that they will bioaccumulate pollutants. The goal of this study was to quantify and identify plastic and cellulosic micro-fragments and microfibers present in the soft body of clams (n = 21), collected from Fildes Bay near sewage and wastewater discharges. Plastic and cellulose microfragments and microfibers were counted, and their compositions were determined using FT-IR. All 21 individuals sampled contained fragments and fibers, with a total of 900 items detected (42.86 ± 25.36 mean ± SD items per individual), or 1.82 items g.wet mass -1 . 58 % of items were cellulose and 22 % plastic. Considering the plastic polymer compositions, 28.57 % were polyethylene terephthalate (PET), 21.43 % acrylic, 14.29 % high-density polyethylene (HDPE), 14.29 % Polypropylene (PP), 7.14 % ultra-high drawn polyethylene filament (UHMWPE), 7.14 % polyester and 7.14 % Polyethylene. The quantities and prevalence of MP in L. elliptica were higher than those found in other Antarctic marine species, and even in bivalves from populated regions of the world. Our work assessed the pollution status of L. elliptica near an effluent of wastewater plants and found that 95 % of individuals displayed MP and 100 % microfibers that could impact their population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The adoption of minimally invasive techniques to perform mitral valve repair surgery is increasing. This is enhanced by the compelling evidence of satisfactory short-term results and lower major morbidity. We analyzed mid-term follow-up results of our experience, and further compared two techniques: isolated leaflet resection and neochord implantation for posterior leaflet prolapse., Methods: Data for all consecutive endoscopic mitral valve repairs via video-assisted right anterior mini-thoracotomy were analyzed between December 2012 and September 2021. The early and mid-term follow-up results were ascertained. The main outcome was the incidence of mortality and the recurrence of significant mitral regurgitation during follow-up which were summarized by the Kaplan-Meier estimator and compared between treatment arms using the stratified log-rank test. Secondary outcomes were the early-postoperative results including 30-days mortality and the occurrence of major complications., Results: A total of 309 patients were included. Along with ring annuloplasty, 136 (44.4%) patients received posterior leaflet resection (122 isolated) whereas 97 (31.1%) underwent posterior leaflet chords implantation (88 isolated). Forty-nine patients had annuloplasty alone. In-hospital mortality was 1.0%. Mean follow-up was 28.8 ± 22.0 months (maximum 8.3 years). Kaplan-Meier survival rate at 5 years was 97.3 ± 1.0%, mitral regurgitation ([Formula: see text]3+) or valve reoperation free-survival at 5 years was estimated as 94.5 ± 2.3%. Subgroup time-to-event analysis for the indexed outcomes showed no statistical significance between the techniques., Conclusions: Endoscopic mitral valve repair is safe and associated with excellent short- and mid-term outcomes. No differences were found between leaflet resection and gore-tex chords implantation for posterior leaflet prolapse., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Mirror neurons (MNs) were first described in a seminal paper in 1992 as a class of monkey premotor cells discharging during both action execution and observation. Despite their debated origin and function, recent studies in several species, from birds to humans, revealed that beyond MNs properly so called, a variety of cell types distributed among multiple motor, sensory, and emotional brain areas form a 'mirror mechanism' more complex and flexible than originally thought, which has an evolutionarily conserved role in social interaction. Here, we trace the current limits and envisage the future trends of this discovery, showing that it inspired translational research and the development of new neurorehabilitation approaches, and constitutes a point of no return in social and affective neuroscience., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: There are many reasons for the increase in post-operative mortality and morbidity in patients undergoing surgery. In fact, an activated inflammatory state before cardiac surgery, can potentially worsen the patient's prognosis and the effects of this preoperative inflammatory state in the medium-term remains unknown., Methods: There were 470 consecutive patients who underwent cardiac surgery, and were divided in three groups according to the median values of preoperative C-reactive protein (CRP) and fibrinogen (FBG): The first group was the low inflammatory status group (LIS) with 161 patients (CRP < 0.39 mg/dL and FBG < 366 mg/dL); the second was the medium inflammatory status group (MIS) with 150 patients (CRP < 0.39 mg/dL and FBG ≥ 366 mg/dL or CRP ≥ 0.39 mg/dL and FBG < 366 mg/dL,); and the third was the high inflammatory status group (HIS) with 159 patients (CRP ≥ 0.39 mg/dL and FBG ≥ 366 mg/dL,)., Results: The parameters to be considered for the patients before surgery were similar between the three groups except, however, for age, left ventricular ejection fraction (LVEF) and the presence of arterial hypertension. The operative mortality was not significantly different between the groups (LIS = 2.5%, MIS = 6%, HIS = 6.9%, p = 0.16) while mortality for sepsis was significantly different (LIS = 0%, MIS = 1.3%, HIS = 3.7%, p = 0.03). The infections were more frequent in the HIS group ( p = 0.0002). The HIS group resulted in an independent risk factor for infections (relative risk (RR) = 3.1, confidence interval (CI) = 1.2-7.9, p = 0.02). During the 48-months follow-up, survival was lower for the HIS patients. This HIS group (RR = 2.39, CI = 1.03-5.53, p = 0.05) and LVEF (RR = 0.96, CI = 0.92-0.99, p = 0.04) resulted in independent risk factors for mortality during the follow-up., Conclusions: The patients undergoing cardiac surgery with a preoperative highly activated inflammatory status are at a higher risk of post-operative infections. Furthermore, during the intermediate follow-up, the preoperative highly activated inflammatory status and LVEF resulted in independent risk factors for mortality., Competing Interests: The authors declare no conflicts of interest.

Introduction: Ischemic heart diseases are the major leading cause of death worldwide. Revascularization procedures dramatically reduced the overall risk for death related to acute coronary syndromes. Two kinds of myocardial revascularization can grossly be outlined: percutaneous coronary intervention (PCI) and surgical coronary artery bypass graft intervention (CABG). The net clinical benefit coming from these two kinds of procedures is still under debate., Methods: We have traced the state-of-the-art background about myocardial revascularization procedures by comparing the most important trials dealing with the evaluation of percutaneous interventions versus a surgical approach to coronary artery diseases., Results: Both PCI and CABG have become effective treatments for revascularization of patients suffering from advanced CAD. The advance in technology and procedural techniques made PCI an attractive and, to some extent, more reliable procedure in the context of CAD. However, there are still patients that cannot undergo PCI and have to be rather directed towards CABG., Conclusion: CABG still remains the best strategy for the treatment of multiple vessel CAD due to improved results in term of survival and freedom from reintervention. Anyway, a systematic, multidisciplinary approach to revascularization is the fundamental behaviour to be chased in order to effectively help the patients in overcoming its diseases. The creation of the "heart team" seems to be a good option for the correct treatment of patients suffering from stable and unstable CAD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Minimally invasive valve surgery (MIVS) is associated with improved clinical outcome but longer cardiopulmonary bypass (CPB) time. The aim of the present study is to compare inflammatory and coagulation parameters in patients undergoing minimally invasive or standard valve surgery., Methods: A prospective non-randomized study was performed enrolling 79 patients undergoing mitral (20 right mini-thoracotomy and 18 standard sternotomy) and aortic valve (20 mini-sternotomy and 21 standard sternotomy) procedures. Blood samples were collected perioperatively to measure prothrombin fragment 1.2 (PF1.2, thrombin generation), plasmin antiplasmin complex (PAP, fibrinolysis), interleukin-6 (IL-6, inflammation). Plasma free haemoglobin (f-Hb) was assessed to evaluate haemolysis., Results: Patients in the minimally invasive group were younger and had less comorbidities CPB and cross-clamp times were comparable considering both aortic and mitral procedures, but longer in the mini-thoracotomy group. IL-6 and PAP were reduced in the minimally invasive group, particularly 2 h after CPB (respectively 102 ± 114 vs 34 ± 49 pg/ml, P < 0.001 and 2137 ± 1046 vs 1207 ± 675 ng/ml, P < 0.001), PF1.2 was also reduced during and after the operation (688 ± 514 vs 571 ± 470, P = 0.02; 1600 ± 1185 vs 1042 ± 548, P < 0.001; 1487 ± 676 vs 1042 ± 541). Despite the use of vacuum-assisted active venous drainage (VAVD) f-Hb was significantly reduced in the minimally invasive group. The other routine biomarkers such as C-reactive protein, fibrinogen and cTnI were also reduced in the minimally invasive group., Conclusions: In a selected cohort of patients MIVS is associated to reduced inflammatory reaction and coagulopathy, supporting the clinical evidence of reduced postoperative bleeding and lower transfusion rate. Our data offer further suggestion supporting the adoption of minimally invasive approaches., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Acute kidney injury (AKI) is a common complication following cardiac surgery. Cardiopulmonary bypass elicits coagulation and inflammation activation and oxidative stress, all involved in AKI but never simultaneously assessed. We aimed to evaluate relations between oxidative stress, inflammatory and coagulation systems activation and postoperative renal function in patients with normal preoperative renal function., Methods: Forty-one high-risk patients (EuroSCORE >6 and preoperative haemoglobin <12 g/dl in women and <13 g/dl in men) were prospectively enrolled. Prothrombin fragment 1.2 (coagulation marker), interleukin-6 and interleukin-10 (pro/anti-inflammatory markers) and 8-oxo-2'-deoxyguanosine (oxidative stress marker) were evaluated until postoperative day 5., Results: Patients were divided into two groups according to estimated glomerular filtration rate reduction observed postoperatively (reduction <25% in 26 patients: NO-AKI group; reduction >25% in 15 patients: AKI group). No differences were found for inflammatory markers. Oxidative stress slightly increased in the AKI group. Twenty-four hours after the operation prothrombin fragment 1.2 levels were significantly higher in the AKI group (506.6 ± 548 vs. 999 ± 704.1 pmol/l; P = 0.018), and they were independently associated with estimated glomerular filtration rate reduction, with an area under the receiving operating characteristic of 0.744., Conclusion: Thrombin generation is higher in patients with renal function worsening, and it is an independent risk factor for AKI in patients with anaemia, possibly leading to microcirculation impairment and tubular cells damage.

Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752). A substudy was conducted in 2 sites to collect blood samples perioperatively to measure prothrombin fragment 1.2 (PF1+2, thrombin generation), plasmin-antiplasmin complex (PAP, fibrinolysis), platelet factor 4 (PF4 platelet activation), and fibrinogen. Eighty-one patients were enrolled in the substudy (37 placebo vs 44 in treatment group). No difference in clinical outcome was detected, including postoperative bleeding and need for blood products transfusion. All patients showed changes of all plasma biomarkers with greater values than baseline in both groups. This reaction was attenuated significantly in the treatment group for PF1.2 (P = 0.040) and PAP (P = 0.042) values at the first intraoperative measurement. No difference between groups was detected for PF4. Methylprednisolone treatment attenuates activation of coagulation system in high-risk patients undergoing CPB surgery. Reduction of thrombin generation and fibrinolysis activation may lead to reduced blood loss after surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: To conduct a comparative study of cardiac troponin I (cTnI) and MB isoenzyme of serum creatine kinase (CK-MB) after different cardiac surgeries., Methods: Consecutive cardiac operations under cardiopulmonary bypass (200 adults, 144 men, 68 ± 11 years): 67 coronary artery bypass graft (CABG), 27 aortic valve surgery, 21 mitral valve surgery, 11 thoracic aorta surgery, and 74 combined surgery. Postoperative cTnI and CK-MB were measured on admission to the ICU and at fixed time until the fifth postoperative day., Results: Peak values of cTnI (median 5.8 ng/ml; interquartile range 3.6-11.9) and CK-MB (29.0 ng/ml; 15.6-60.4) were reached mainly within 18 h after the end of surgery (85% of cTnI and 95% of CK-MB highest determinations) without differences among groups. Cardiopulmonary bypass and cross-clamp time significantly correlated with markers' peak values. At multivariate analysis, mitral valve surgery showed greater cTnI, CK-MB, and their cumulative area under the curve than other isolated procedures. Thoracic aorta surgery showed lower cumulative area under the curve for both markers than CABG and combined surgery. Mitral valve surgery had significant later reduction of both markers in comparison with other procedures. No patient in mitral valve surgery group reached cTnI values in the normal laboratory range within 5 postoperative days., Conclusion: Release pattern of cTnI and CK-MB after heart surgery depends on the type of procedure. Mitral valve surgery was characterized by highest and longest elevation of postoperative markers' concentration. Determinants of differences in myocardial injury biomarkers and their prognostic value after valve surgery should be accurately assessed.

Objective: To evaluate the effects of prophylactic perioperative corticosteroid administration, compared with placebo, on postoperative mortality and clinical outcomes (renal dysfunction, duration of mechanical ventilation, and ICU length of stay) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass., Data Sources: MEDLINE and Cochrane Library were screened through August 2013 for randomized controlled trials in which perioperative steroid treatment was adopted., Study Selection: Included were randomized controlled trials conducted on pediatric population that reported clinical outcomes about mortality and morbidity., Data Extraction: Eighty citations (PubMed, 48 citations; Cochrane, 32 citations) were identified, of which 14 articles were analyzed in depth and six articles fulfilled eligibility criteria and reported mortality data (232 patients), two studies reported ICU length of stay and mechanical ventilation duration (60 patients), and two studies reported renal dysfunction (49 patients)., Data Synthesis: A nonsignificant trend of reduced mortality was observed in steroid-treated patients (11 [4.7%] vs 4 [1.7%] patients; odds ratio, 0.41; 95% CI, 0.14-1.15; p = 0.089). Steroids had no effects on mechanical ventilation time (117.4 ± 95.9 hr vs 137.3 ± 102.4 hr; p = 0.43) and ICU length of stay (9.6 ± 4.6 d vs 9.9 ± 5.9 d; p = 0.8). Perioperative steroid administration reduced the prevalence of renal dysfunction (13 [54.2%] vs 2 [8%] patients; odds ratio, 0.07; 95% CI, 0.01-0.38; p = 0.002)., Conclusion: Despite a demonstrated attenuation of cardiopulmonary bypass-induced inflammatory response by steroid administration, a systematic review of randomized controlled trials performed so far reveals that steroid administration has potential clinical advantages (lower mortality and significant reduction of renal function deterioration). A larger prospective randomized study is needed to verify clearly the effects of steroid prophylaxis in pediatric patients.

Background: Antithrombin (AT) concentrations are reduced after cardiac surgery with cardiopulmonary bypass compared with the preoperative levels. Low postoperative AT is associated with worse short- and mid-term clinical outcomes. The aim of the study is to evaluate the effects of AT administration on activation of the coagulation and fibrinolytic systems, platelet function, and the inflammatory response in patients with low postoperative AT levels., Methods: Sixty patients with postoperative AT levels of less than 65% were randomly assigned to receive purified AT (5000 IU in three administrations) or placebo in the postoperative intensive care unit. Thirty patients with postoperative AT levels greater than 65% were observed as controls. Interleukin 6 (a marker of inflammation), prothrombin fragment 1-2 (a marker of thrombin generation), plasmin-antiplasmin complex (a marker of fibrinolysis), and platelet factor 4 (a marker of platelet activation) were measured at six different times., Results: Compared with the no AT group and control patients, patients receiving AT showed significantly higher AT values until 48 hours after the last administration. Analysis of variance for repeated measures showed a significant effect of study treatment in reducing prothrombin fragment 1-2 (p=0.009; interaction with time sample, p=0.006) and plasmin-antiplasmin complex (p<0.001; interaction with time sample, p<0.001) values but not interleukin 6 (p=0.877; interaction with time sample, p=0.521) and platelet factor 4 (p=0.913; interaction with time sample, p=0.543). No difference in chest tube drainage, reopening for bleeding, and blood transfusion was observed., Conclusions: Antithrombin administration in patients with low AT activity after surgery with cardiopulmonary bypass reduces postoperative thrombin generation and fibrinolysis with no effects on platelet activation and inflammatory response., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) after cardiac operations is a serious complication associated with postoperative mortality. Multiple factors contribute to AKI development, principally ischemia-reperfusion injury and inflammatory response. It is well proven that glucocorticoid administration, leukocyte filter application, and miniaturized extracorporeal circuits (MECC) modulate inflammatory response. We conducted a systematic review of randomized controlled trials (RCTs) in which one of these inflammatory system modulation strategies was used, with the aim to evaluate the effects on postoperative AKI. MEDLINE and Cochrane Library were screened through November 2011 for RCTs in which an inflammatory system modulation strategy was adopted. Included were trials that reported data about postoperative renal outcomes. Because AKI was defined by different criteria, including biochemical determinations, urine output, or dialysis requirement, we unified renal outcome as worsening renal function (WRF). We identified 14 trials for steroids administration (931 patients, WRF incidence [treatment vs. placebo]: 2.7% vs. 2.4%; OR: 1.13; 95% CI: 0.53-2.43; P = 0.79), 9 trials for MECC (947 patients, WRF incidence: 2.4% vs. 0.9%; OR: 0.47; 95% CI: 0.18-1.25; P = 0.13), 6 trials for leukocyte filters (374 patients, WRF incidence: 1.1% vs. 7.5%; OR: 0.18; 95% CI: 0.05-0.64; P = 0.008). Only leukocyte filters effectively reduced WRF incidence. Not all cardiopulmonary bypass-related anti-inflammatory strategies analyzed reduced renal damage after cardiac operations. In adult patients, probably other factors are predominant on inflammation in determining AKI, and only leukocyte filters were effective. Large multicenter RCTs are needed in order to better evaluate the role of inflammation in AKI development after cardiac operations., (© 2013, Copyright the Authors. Artificial Organs © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.)

Objectives: To assess the incidence of incomplete heparin reversal and heparin rebound after cardiac surgery with cardiopulmonary bypass (CPB) and the ability of the activated coagulation time (ACT) and thromboelastography (TEG) to detect these phenomena., Design: Prospective single-center study., Setting: University hospital., Participants: Forty-one patients undergoing elective cardiac surgery with CPB and with normal preoperative TEG parameters., Interventions: ACT, TEG, and plasma heparin levels were measured in all patients at 5 different times between 20 minutes and 3 hours after protamine administration. The variability of TEG reaction time (R) with and without heparinase (delta-R [DR]) was used to detect the presence of residual heparin., Measurements and Main Results: Plasma heparin expressed as anti-FXa activity was detected in 180 (88%) samples. At univariate analysis, ACT, R-kaolin (R-k), and DR significantly correlated with plasma heparin concentration (respectively, p = 0.007, p = 0.006, and p = 0.002). At multivariate analysis, R-k and DR remained associated with plasma heparin concentration (respectively, p = 0.014 and p = 0.004). Greater quartiles of heparin were associated with higher values of R-k and DR. Combined procedures had significantly lower DR than isolated procedures (p = 0.017), and CPB time and heparinization time positively correlated with R-k (respectively, p = 0.044 and p = 0.022). No association was observed between heparin concentration, ACT, and TEG parameters with postoperative bleeding and need for blood and blood components transfusions., Conclusions: Heparin rebound and incomplete heparin reversal are very common phenomena after cardiac surgery with CPB; ACT is not able to detect residual heparin activity, whereas TEG analysis with and without heparinase allows the diagnosis of heparin rebound., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The receptor activator of the nuclear factor kappa-B (NF-κB) ligand (RANKL), its membrane receptor RANK and its decoy receptor osteoprotegerin (OPG) are all members of the tumour necrosis factor family involved in bone metabolism and immune response. We evaluated the activation of the OPG/RANKL/RANK pathway in patients undergoing cardiac surgery with and without cardiopulmonary bypass (CPB)., Methods: Twenty consecutive patients undergoing elective coronary artery surgery were enrolled in the study and assigned either to the on-pump or to the off-pump group. Pre- and postoperative serum levels of OPG and RANKL were evaluated by enzyme-linked immunosorbent assay; gene expression of OPG, RANKL, RANK and NF-κB p50 subunits were determined by real-time polymerase chain reaction in peripheral blood T-cells and monocytes., Results: Serum levels of OPG significantly increased after surgery in both groups, whereas serum levels of RANKL did not differ over time. T-cells from the on-pump group showed increased gene expression of OPG, RANKL and RANK after the intervention, whereas no mRNA variation for these genes was detected in T-cells from off-pump patients. Gene expression of p50 subunit increased in T-cells and monocytes from both groups., Conclusions: Cardiac surgery induces the activation of the OPG/RANKL/RANK pathway; both on- and off-pump procedures are associated with increased postoperative OPG serum levels and up-regulation of the NF-κB p50 subunit.

Objective: Cardiopulmonary bypass (CPB) systems without a venous reservoir rarely are adopted clinically. The effects of a biocompatible CPB system with a venous reservoir were evaluated on the activation of the coagulation and inflammatory systems., Design: A prospective, randomized controlled trial., Setting: A university hospital (single center)., Participants: Eighty-three coronary artery bypass graft (CABG) surgery patients were assigned to the Physio group (closed venous reservoir, phosphorylcholine coating, and no cardiotomy suction) or the Standard group (open, noncoated, and cardiotomy suction used)., Methods: Blood samples were obtained at 6 different time points before, during, and after surgery. Nuclear factor-kB (NF-κB) was evaluated before surgery and 2 and 24 hours after surgery. Myocardial damage was evaluated measuring cardiac troponin I., Measurements and Main Results: Interleukin (IL)-6 (a marker of inflammation), prothrombin fragment 1-2 (PF-1.2, a marker of thrombin generation), plasmin-antiplasmin complex (PAP, a marker of fibrinolysis), and platelet factor 4 (PF4, a marker of platelet activation) were measured. The DNA binding activity of proinflammatory transcription factor NF-κB was quantified in the isolated lymphomonocyte cells. Surgery caused changes of all plasma biomarkers. This reaction was attenuated strongly in the Physio group; PF-1.2, PAP, and PF4 all were decreased significantly. In the Physio group, a significantly lower cardiac troponin I release was observed postoperatively. After surgery, NF-κB activity was reduced in the Physio group although this difference was not statistically significant., Conclusions: A multimodal strategy using a closed and phosphorylcholine-coated CPB circuit together with the avoidance of cardiotomy suction reduced activation of the coagulation and fibrinolytic systems intraoperatively, although these changes did not persist postoperatively. However, no difference in clinical outcome was appreciated on a larger scale., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Surgery for acute aortic dissection (AAD) is frequently complicated by excessive postoperative bleeding and blood product transfusion. Blood flow through the nonendothelialized false lumen is a potential trigger for the activation of the hemostatic system; however, the physiopathology of the aortic dissection induced coagulopathy has never been precisely studied. The aim of the present study is the evaluation of the coagulation and fibrinolytic systems and platelet activation in patients undergoing surgery for AAD., Methods: Eighteen patients undergoing emergent surgery for Stanford type A AAD were enrolled in the study. The activation of the coagulation and fibrinolytic systems and platelet activation were evaluated at 6 different time points before, during, and after the operation, measuring prothrombin fragment 1.2 (F1.2), plasmin-antiplasmin complex, and platelet factor 4, respectively., Results: All measured biomarkers were increased before, during, and after the operations indicating a systemic activation of coagulation, fibrinolysis, and platelets. These changes were pronounced even preoperatively (T0), and soon after the beginning of cardiopulmonary bypass (T1) when the influence of hypothermia and prolonged cardiopulmonary bypass time were not yet involved. Time from symptom onset to intervention inversely correlated with preoperative F1.2 (r=-0.75; p=0.002) and plasmin-antiplasmin levels (r=-0.57; p=0.034)., Conclusions: Blood flow through the false lumen is a powerful activator of the hemostatic system even before the operation. This remarkable activation may influence postoperative outcome of AAD patients., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In patients with acute aortic dissection, an early diagnosis is essential to anticipate aortic rupture, cardiac tamponade, organ ischemia and improve surgical results. A specific blood laboratory marker able to rule out the presence of aortic dissection has not been identified yet. Recently, several studies suggested using D-dimers as a negative predicting test to rule out diagnosis of acute aortic dissection in patients presenting with chest pain. In 61 patients with confirmed aortic dissection, preoperative D-dimers were assayed and correlated with time from symptom onset and extension of the false lumen dissection (according with De Bakey classification). Abnormal D-dimers values were considered those being greater than 400 microg/l. D-dimers values were above 400 microg/l in 50 patients (82%) and below 400 microg/l in 11 patients (18%). There was no correlation between preoperative D-dimers values and time from symptoms onset (r = -0.232; P = 0.1). We found that D-dimers are not always elevated in patients presenting with acute aortic dissection. Given the potential devastating effects of denying the diagnosis of acute aortic dissection with consequent delay of adequate treatment, a word of caution regarding the negative predictive value of D-dimer test in the diagnosis of aortic dissection seems warranted.

The mycotoxin ochratoxin A (OTA), an ubiquitous contaminant of food products endowed with a wide spectrum of toxicity, affects several functions of mononuclear leukocytes. Monocytes/macrophages play a major role in fibrin accumulation associated with immune-inflammatory processes through the production of tissue factor (TF) and plasminogen activator inhibitor 2 (PAI-2). We studied the effect of OTA on TF and PAI-2 production by human blood mononuclear cells (MNC). The cells were incubated for 3 or 18 h at 37 degrees C with non toxic OTA concentrations in the absence and in the presence of lipopolysaccharide (LPS) or other inflammatory agents. TF activity was measured by a one-stage clotting test. Antigen assays were performed by specific ELISAs in cell extracts or conditioned media and specific mRNAs were assessed by RT-PCR. OTA had no direct effect on TF and PAI-2 production by MNC. However, OTA caused a dose-dependent reduction in LPS-induced TF (activity, antigen and mRNA) and PAI-2 (antigen and mRNA) production with >85% inhibition at 1 mug/ml. Similar results were obtained when monocyte-enriched preparations were used instead of MNC. TF production was also impaired by OTA (1 mug/ml) when MNC were stimulated with phorbol myristate acetate (98% inhibition), IL-1beta (83%) or TNF-alpha (62%). The inhibition of TF and PAI-2 induction might represent a hitherto unrecognized mechanism whereby OTA exerts immunosuppressant activity.

The prothrombin gene mutation G20210A is a common risk factor for thrombosis and has been reported to cause APC resistance. However, the inhibition of thrombin formation by APC not only limits fibrin formation but also stimulates fibrinolysis by reducing TAFI activation. We evaluated the influence of prothrombin G20210A mutation on the anticoagulant and fibrinolytic activities of APC (1 microg/ml). Thirty-two heterozygous carriers and 32 non carriers were studied. APC anticoagulant activity was assessed by aPTT prolongation whereas APC fibrinolytic activity was determined by a microplate clot lysis assay. APC-induced aPTT prolongation was markedly less pronounced in carriers than in non carriers. On the contrary, fibrinolysis time was shortened by APC to a comparable extent in both groups. Accordingly, prothrombin levels were strongly correlated with APC-induced aPTT prolongation but not with APC-induced shortening of lysis time. The addition of purified prothrombin to normal plasma (final concentration 150%) caused APC resistance in the clotting assay over the whole range of tested APC concentrations (0.125-1.5 microg/ml). In the fibrinolytic assay, instead, prothrombin supplementation made the sample resistant to low but not to high concentrations of APC (>0.5 microg/ml). Thrombin and TAFIa determination in the presence of 1 microg/ml APC revealed that hyperprothrombinemia, although capable of enhancing thrombin generation, was unable to induce detectable TAFIa formation. It is suggested that APC resistance caused by hyperprothrombinaemia does not translate in impaired fibrinolysis, at least in the presence of high APC levels, because the increase in thrombin formation is insufficient to activate the amount of TAFI required to inhibit plasminogen conversion. These data might help to better understand the relationship between thrombin formation and fibrinolysis down-regulation.

1. The abdominal frog skin was mounted between two chambers containing Ringer with 1 mM-Na on the outside and 115 mM-Na on the inside. When the Na concentration of the outer solution ([Na](o)) is instantaneously raised from 1 to 50 mM, the short circuit current (I) increases to a new value in less than a second, and becomes essentially time-independent. Only in a few experiments was it observed to increase further, although at a much slower rate.2. At a time t after this increase, the addition of 10(-4)M amiloride to the outer solution produces an exponential decrease of I. The area under this exponential curve is generally taken to reflect the existence of a Na- transporting compartment (NaTC).3. The amount of Na represented by NaTC is a function of t: it increases from 1.7 x 10(-9) mole. cm(-2), at t = 10 sec, to 22.8 x 10(-9) mole. cm(-2) at t = 10 min.4. In view of the fact that (a) I is not a function of the size of the ;NaTC' and (b) that whereas I reaches a steady value in a fraction of a second the size of NaTC keeps increasing for minutes, it is proposed that the ;NaTC' represents an amount of Na which is not located along the main route of transepithelial transport.5. On the assumption that the NaTC is located in a cellular compartment and that, in order to accumulate in this compartment Na should be accompanied by a permeable anion, a series of experiments were performed with Ringer in which Cl(-) was replaced by gluconate. It was observed as expected, that NaTC in gluconate is 164 times smaller than in Cl(-), but I only decreases to one half its value in Cl(-) Ringer.