Placental cartography of NADPH oxidase (NOX) family proteins: Involvement in the pathophysiology of preeclampsia.

The placenta is an essential organ for fetal development. During the first trimester, it undergoes dramatic changes as it develops in an environment poor in oxygen (around 2-3%). From about 10 gestational weeks, oxygen levels increase to 8% in the intervillous chamber. These changes are accompanied by modulation of the activity of NADPH oxidase, a major source of production of reactive oxygen species in the first trimester of pregnancy. The NOX complex is composed of seven different proteins (NOX1-5 and DUOX1-2) whose placental involvements during physiological and pathological pregnancies are largely unknown. The aim of the study was to produce a cartography of NOX family proteins, in terms of RNA, protein expression, and localization during physiological pregnancy and in the case of preeclampsia (PE), in a cohort of early-onset PE (n = 11) and late-onset PE (n = 7) cases. NOX family proteins were mainly expressed in trophoblastic cells (NOX4-5, DUOX1) and modulated during physiological pregnancy. NOX4 underwent an unexpected and hitherto unreported nuclear translocation at term. In the case of PE, two groups stood out: NOX1-3, superoxide producers, were down-regulated (p < 0.05) while NOX4-DUOX1, hydrogen peroxide producers, were up-regulated (p < 0.05), compared to the control group. Mapping of placental NOX will constitute a reference and guide for future investigations concerning its involvement in the pathophysiology of PE.

Comparison of blood gas results obtained on Abbott i-Stat® and on Radiometer ABL 800 Flex® analyzers Impact for the clinical decision

Background: Point of care testing (POCT) tests are needed to assess severity and to help for triage in hospital and in prehospital settings. Before their use, the analytical performances of POCTs have to be compared with central laboratory reference methods. In this study, we describe the comparability of results obtained by either the Abbott i-STAT® System POCT handheld device or the blood gases analyzer of the central laboratory of our hospital. Methods: Sample blood from 37 septic patients admitted to the intensive care unit (ICU) were assayed by Abbott i-STAT® System POCT and Radiometer ABL800 Flex® lab analyzer. Studied parameters were as follows: pH, pO2, pCO2, base excess (BE), HCO3- and lactate. Comparability was evaluated using Bland-Altman method. The clinical value for possible mismatch issued of values differences was also assessed. Results: Quite acceptable correlations in results of POCT and laboratory analyzer were observed with R² most of time above 0.85. Bland-Altman analysis showed a bias of 1.26% for Abbott i-STAT® System POCT vs laboratory. Conclusion: Abbott i-STAT® System POCT handheld device is comparable to Radiometer ABL800 Flex® lab analyzer and concordant with laboratory analysis. Abbott i-STAT® System POCT handled device could be used in the prehospital settings in order to evaluate the severity of sepsis.

Contexte: Les dispositifs médicaux de biologie délocalisée peuvent être utiles pour évaluer la gravité et aider au triage des patients à la fois en milieu hospitalier mais aussi en milieu préhospitalier. Avant leur utilisation, les performances analytiques de ces dispositifs médicaux doivent être comparées aux méthodes de référence des laboratoires hospitaliers. Dans cette étude, nous décrivons la comparabilité des résultats obtenus soit par le dispositif portable Abbott i-STAT® avec ceux fournis par l'analyseur de gaz du sang du laboratoire central de notre hôpital. Méthodes: Des échantillons de sang provenant de 37 patients septiques admis en réanimation ont été analysés par le système Abbott i-STAT® et l'analyseur de laboratoire Radiometer ABL800 Flex®. Les paramètres étudiés étaient les suivants : pH, pO2, pCO2, excès de base (BE), HCO3- et lactate. La comparabilité a été évaluée par la méthode de Bland-Altman. La valeur clinique de l'éventuelle inadéquation issue des différences de valeurs a également été évaluée. Résultats: Des corrélations tout à fait acceptables entre les résultats du système Abbott i-STAT® et de l'analyseur de laboratoire ont été observées, avec un R² le plus souvent supérieur à 0,85. L'analyse Bland-Altman a montré un biais de 1,26 % pour le système Abbott i-STAT® par rapport aux résultats fournis par l'analyseur du laboratoire. Conclusion: Le dispositif de biologie délocalisée Abbott i-STAT® est comparable et concordant avec l'analyseur de laboratoire Radiometer ABL800 Flex®. Le dispositif Abbott i-STAT® System POCT pourrait être utilisé en milieu préhospitalier afin d'évaluer la gravité de patients atteints de sepsis.

Human catalase gene promoter haplotype and cardiometabolic improvement after bariatric surgery.

Although its powerful impact on most co-morbidities has been widely demonstrated, the metabolic outcomes of bariatric surgery (BS) show a great heterogeneity among patients. Haplotypes of one of the major antioxidant enzyme, catalase (CAT), are associated with hypertension, dyslipidemia, and diabetes. The haplotype referred to as CAT1 includes homozygous carriers of CATH1 [-844G,-89A,-20T], whereas CAT2 haplotype includes heterozygous carriers (CATH1/CATH2) and CATH2 homozygous [-844A,-89T,-20C]. The aim of our study was to evaluate the impact of CAT1 and CAT2 haplotypes on traditional cardiovascular and metabolic markers one year after BS in a women population. The 294 women with a body mass index (BMI) >35 kg/m2 were followed-up for one year after BS, monitoring their anthropometric, metabolic and inflammatory parameters. CAT1 patients had significantly improved diastolic blood pressure (DBP) and Creactive protein (CRP) levels compared to CAT2 one year after BS. In untreated women at baseline, the change of CRP one year after BS was higher in CAT1 patients. In the population of women receiving at least one anti-lipidic, anti-hypertensive or anti-diabetic treatment at baseline, DBP and fat mass were lower one year after BS in CAT1 patients and the greater change of fat mass was associated with a higher change of adiponectin. The results highlight the beneficial impact of the CAT1 haplotype on traditional cardiovascular and metabolic parameters after BS. Our findings suggest that the CAT1 haplotype could be implicated in the level of metabolic and cardiovascular improvement after BS.

Interleukin-10 Production in Response to Amyloid-ß Differs between Slow and Fast Decliners in Patients with Alzheimer's Disease.

We investigated IL-10 and IL-6 production in amyloid-ß (Aß) stimulated peripheral blood mononuclear cells (PBMCs) in twenty Alzheimer's disease (AD) patients with slow progression, eleven with fast progression, and twenty age-matched controls. Promoter polymorphisms in IL-10 (position -592, -819, -1082), IL-6 (-174), transforming growth factor-ß1 (TGF-ß1) (-10, -25), interferon-γ (IFN-γ) (-874), and tumor necrosis factor-α (TNF-α) (-308) genes were analyzed. IL-10 production after Aß stimulation was high in PBMCs from slow decliners and almost completely abrogated in fast decliners. Association between AA IFN-γ low-producing genotype and fast progression was demonstrated. Investigations in a larger sample will clarify these findings.

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age.

High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet.

Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus murinus), using ultra-high-performance liquid chromatography-quadrupole time of flight.

The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg-1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism.

Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans.

Several recently published clinical trials have extended our knowledge on the use of resveratrol (RVT) to treat several human pathological and metabolic disorders. Herein, we present insights into the metabolism, biological effects, and toxicity of RVT in humans. Recent data show that RVT exhibits antioxidant and anti-inflammatory activities. It can also improve glucose and lipid metabolism, it acts on cardiovascular parameters, and can modify some pathways involved in carcinogenesis. However, these effects are mostly tiny and the results are sometimes controversial as they depend on the protocols (i.e. dose, form of administration, patients' characteristics, adjuvant therapy, etc.). Toxicological data confirm that RVT is well tolerated. Any adverse effects (mainly concerning the abdomen), at doses of ≥0.5 g/day for long periods, remain moderate and reversible. Nevertheless, the efficacy and safety of RVT need to be further investigated.

Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice.

Aging leads to increased insulin resistance and arterial dysfunction, with oxidative stress playing an important role. This study explored the metabolic and arterial effects of a chronic treatment with resveratrol, an antioxidant polyphenol compound that has been shown to restore insulin sensitivity and decrease oxidative stress, in old mice with or without a high-protein diet renutrition care. High-protein diet tended to increase insulin resistance and atheromatous risk. Resveratrol improved insulin sensitivity in old mice fed standard diet by decreasing homeostasis model of assessment-insulin resistance and resistin levels. However, resveratrol did not improve insulin resistance status in old mice receiving the high-protein diet. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and diminishing aortic distensibility. In conclusion, we demonstrate that resveratrol has beneficial or deleterious effects on insulin sensitivity and arterial function, depending on nutritional status in our models.

Relationship between catalase haplotype and arterial aging.

BACKGROUND: Although many conventional factors have been associated with the development of arterial aging, cardiovascular diseases remain the first cause of death in old age. Therefore, identification of new risk factors may prove promising for monitoring this serious health problem. Oxidative stress and particularly catalase (CAT), an antioxidant enzyme, play an important role in endothelial cell pathophysiology, in shear stress response and ultimately in arterial aging. OBJECTIVE: Examine the relationships between CAT haplotypes and phenotypes of arterial aging (mean internal diameter, mean intima-media thickness of the common carotid arteries (CCA), presence of atheromatous plaques) in two French cohorts. METHODS AND RESULTS: 564 middle-aged French individuals (mean age 53 ± 12 years) from two cohorts (ERA and STANISLAS cohorts) were included in the study. Blood pressure, CCA intima-media thickness, CCA internal diameter and number of atheromatous plaques were measured. Catalase rs769214 SNP genotyping was performed. We identified a CAT haplotype that influences arterial aging. Individuals carrying the CAT2 haplotype had a higher mean internal diameter of CCA with aging and/or with an SBP ≥140 mmHg and were associated with a greater number of atheromatous plaques than CAT1 haplotypes carriers. This CAT2 haplotype appeared as an independent risk factor of arterial aging, similarly to previously identified factors such as age, systolic blood pressure, male, sex, tobacco use, hs-CRP, BMI and diabetes. CONCLUSION: The present study highlights the roles of CAT haplotypes in arterial aging and underlines the beneficial impact of the CAT1 haplotype on mean internal diameter of the CCA and atheromatous plaque number as well as on potential associated diseases.

[NGAL: a biomarker of acute and chronic renal dysfunction]. / La lipocaline NGAL : biomarqueur d'altération aiguë et chronique de la fonction rénale.

Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein of 25 kDa belonging to the superfamily of lipocalins, which counts low molecular mass proteins having the capacity to fix the iron. The NGAL presents bacteriostatic properties and is a factor of growth and differentiation, especially in response to renal tissue damage and during the nephrogenesis. Since the past 10 years, numerous clinical studies suggest that urinary and/or blood levels of NGAL could be a relevant biomarker of acute or chronic renal failure, in particular in the context of the diabetic nephropathy. NGAL could be a more sensitive and more specific marker than the albuminuria and might detect the early appearance of the renal lesions, and thus could be useful to prevent or reduce severity of renal function alterations.

Piceatannol is more effective than resveratrol in restoring endothelial cell dimethylarginine dimethylaminohydrolase expression and activity after high-glucose oxidative stress.

Glucose-induced oxidative stress is involved in endothelial dysfunction. Dimethylarginine dimethylaminohydrolase (DDAH) and arginase are regulators of the endothelial NO synthase (eNOS). This study aimed to compare the effect of two polyphenolic antioxidants, resveratrol and piceatannol, on DDAH and arginase pathways in bovine aortic endothelial cells under 25 mM glucose for 24 h. DDAH activity and expression were decreased in these cells as compared to control cells, whereas arginase activity was unchanged. DDAH inhibition led to intracellular accumulation of asymmetric dimethylarginine (ADMA), a natural inhibitor of eNOS. Under these conditions, cell pre-treatment with resveratrol (0.1-10 µM) restored basal DDAH activity and ADMA level with a dose-dependent effect. Piceatannol acted as resveratrol on DDAH pathway but at 10-fold lower concentrations. Resveratrol and piceatannol restored DDAH activity even in the presence of splitomicin, a specific inhibitor of Sirtuin 1. These results suggest potential therapeutic intervention targeting resveratrol or piceatannol administration to improve endothelial dysfunction.

Resveratrol: a relevant pharmacological approach for the treatment of metabolic syndrome?

PURPOSE OF REVIEW: The metabolic syndrome is associated with increased risk for development of both cardiovascular disease and type 2 diabetes in humans. Because experimental data and clinical experience have shown that metabolic syndrome and caloric restriction have, at least partly, opposite pathophysiological pathways, the activation of sirtuins may constitute a pharmacological approach to treat metabolic syndrome. Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction. RECENT FINDINGS: Through its regulatory action of both AMP kinase and the sirtuin sirtuin-1, resveratrol is a natural sirtuin activator that certainly will be the head of a new pharmacological family of drugs targeted on sirtuin-1 activity exacerbation in order to treat/protect from obesity and diabetes, and thus metabolic syndrome. SUMMARY: This review discusses the therapeutic use of resveratrol and sirtuin activators in the context of insulin resistance and obesity, the two main features of metabolic syndrome.

Interest and limits of glomerular filtration rate (GFR) estimation with formulae using creatinine or cystatin C in the malnourished elderly population.

Renal function is often altered in elderly patients. A lot of formulae are proposed to estimate GFR to adjust drug posology. French guidelines recommend the Cockcroft-Gault formula corrected with the body surface area (cCG), but the initially described unadjusted Cockcroft-Gault equation (CG) is mainly used in geriatric clinical practice. International recommendations have proposed the modification of diet in renal disease (MDRD) formula, since several authors recommended the Rule formula using cystatin C (cystC) in particular population. To appreciate the most accurate GFR estimation for posology adaptation in an elderly polypathological population, a cross-sectional study with prospective inclusion was carried out in Charles Foix Hospital. Plasma glucose levels (PGL), creatinine (CREA) levels and serum cystC, albumin (ALB), transthyretin (TTR), C-reactive protein (CRP), orosomucoid (ORO) total cholesterol (tCHOL) levels were determined among 193 elderly patients aged 70 and older. The results showed that in a malnourished, inflamed old population, CG, MDRD and Rule formulae resulted in different estimations of GFR, depending on nutritional and inflammatory parameters. Only cCG estimation was shown to be independent from these parameters. To conclude, cCG seems to be the most accurate and appropriate formula in a polypathological elderly population to evaluate renal function in order to adapt drug posology.

Resveratrol bioavailability and toxicity in humans.

Numerous data are now available on the beneficial properties of the polyphenolic compound resveratrol including its anti-inflammatory and antitumor effects. However, few studies have been performed with resveratrol in humans, and the results of these studies appear fragmentary and sometimes contradictory due to variations in conditions of administration, protocols and methods of assessment. This review article presents the results of recent studies investigating the pharmacokinetics, bioavailability, and toxicity of resveratrol in humans. Resveratrol is well absorbed, rapidly metabolized, mainly into sulfo and glucuronides conjugates which are eliminated in urine. Resveratrol seems to be well tolerated and no marked toxicity was reported. These data are important in the context of human efficacy studies, and they provide further support for the use of resveratrol as a pharmacological drug in human medicine.

[Biology of arterial ageing and arteriosclerosis]. / Biologie du vieillissement artériel et artériosclérose.

Arterial ageing - arteriosclerosis - is characterised by both thickening and stiffening of the walls of large and medium arteries. The molecular and cellular mechanisms (i.e. endothelial dysfunction, matrix remodelling, ...) involved in this process are complex, and at least in part common to atherosclerotic injury. Arterial stiffness is strongly associated with cardiovascular disease and an increased risk of morbidity and mortality. The aim of this review is to provide an update on the pathophysiology and the biological process of arterial ageing and to underline the main difference with atherosclerosis damage process in particularly during the calcification step.

Metformin suppresses high glucose-induced poly(adenosine diphosphate-ribose) polymerase overactivation in aortic endothelial cells.

Overactivation of poly(adenosine diphosphate-ribose) polymerase (PARP), an enzyme involved in cellular response to DNA injury resulting from oxidative and nitrosative stress, is considered to play a key role in the pathogenesis of diabetes complications by promoting numerous vascular dysfunctions. In this study, we examined the ability of metformin, which was reported to possess intrinsic vasculoprotective properties independently of its antihyperglycemic effects, to inhibit PARP activation induced by high glucose concentrations in bovine aortic endothelial cells; and we investigated the potential mechanisms involved in this inhibition. The PARP activity was measured by cellular enzyme-linked immuno-specific assay (CELISA) method; cell poly(ribosyl)ated protein polymer accumulation was evaluated by immunofluorescence. Peroxynitrite anion productions were determined using dihydrorhodamine 123 fluoroprobe; and expression of p47phox subunit of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase was analyzed by Western blot in the absence and presence of protein kinase C and NAD(P)H oxidase inhibitors (calphostin and diphenyleneiodonium chloride, respectively). Our data showed that a therapeutically relevant concentration of metformin (5.10(-5) mol/L) was able to abolish PARP activation, to reduce poly(ribosyl)ated protein polymer accumulation, to decrease intracellular peroxynitrite anion level, and to reverse the overexpression of p47phox in bovine aortic endothelial cells stimulated by 25 mmol/L glucose in a similar manner to that of calphostin or diphenyleneiodonium chloride. Taken together, these results suggest that metformin could inhibit glucose-induced PARP activation through blockade of a protein kinase C-dependent NAD(P)H oxidase activation pathway. We propose that some of the beneficial effects of metformin on vascular endothelial cell functions in diabetes may be related to its inhibitory effect on PARP overactivation and its deleterious consequences.

Benefits and side effects of different vegetable oil vectors on apoptosis, oxidative stress, and P2X7 cell death receptor activation.

PURPOSE: Ocular side effects in patients using eye drops may be due to intolerance to the vector used in eye drops. Castor oil is the commonly used lipophilic vector but has been shown to be cytotoxic. Effects on cells of four oils (olive, camelina, Aleurites moluccana, maize) were compared with those of castor oil in human conjunctival cells. METHODS: Human conjunctival cells were incubated with the oils for 15 minutes. After a 24-hour recovery period, cells were tested for viability, proliferation, apoptosis (P2X7 cell death receptor and caspase 3 activation), intracellular redox potential, and reactive oxygen species production. Fatty acid incorporation in cell membranes was also analyzed. In vivo ocular irritation was assessed using the Draize test. RESULTS: Compared to the four other oils, castor oil was shown to induce significant necrosis and P2X7 cell death receptor and caspase 3 activation and to enhance intracellular reactive oxygen species production. Aleurites moluccana and camelina oils were not cytotoxic and increased cell membrane omega-3 fatty acid content. None of the five tested oils showed any in vivo ocular irritation. CONCLUSIONS: The results demonstrated that castor oil exerts cytotoxic effects on conjunctival cells. This cytotoxicity could explain the side effects observed in some patients using eye drops containing castor oil as a vehicle. The lack of cytotoxic effects observed with the four other oils, Aleurites, camelina, maize, and olive, suggest that they could be chosen to replace castor oil in ophthalmic formulations.

Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-alpha- and IL-1beta-stimulated human synoviocytes from patients with rheumatoid arthritis.

Thioredoxin (Trx) plays several important roles, through changes to sulfhydryl reactions and protein interactions, in controlling cellular signalling processes in RA (rheumatoid arthritis). Trx80, the 10 kDa C-terminal truncated form of Trx, is a potent mitogenic cytokine and is involved in the Th1 response. In the present study, we have investigated the ability of synoviocytes from five RA patients to induce Trx80 after ex vivo stimulation by the pro-inflammatory cytokines IL-1beta (interleukin-1beta) and TNF-alpha (tumour necrosis factor-alpha) or by H(2)O(2). Synoviocytes from five OA (osteoarthritis) patients were used as controls. Immunoprecipitation assays using two different antibodies showed that RA, but not OA, cells expressed intact Trx80 protein in culture even when not stimulated. Treatment with pro-inflammatory cytokines alone or in combination enhanced this basal production and induced the extracellular release of Trx80 by all of the RA cells tested. Under our experimental conditions, the rate of Trx80 release from RA cells was approx. 30% of the total Trx produced. In contrast, Trx80 was not detected in response to H(2)O(2) in RA or OA synoviocyte lysates and their respective culture supernatants, indicating that the oxidative process induced by H(2)O(2) in synoviocytes was unable to modify Trx80 release. Moreover, Trx80 induced synoviocyte proliferation as evaluated by [(3)H]thymidine incorporation. These results highlight the effect of the inflammatory process on the release of both Trx and Trx80 from RA synoviocytes, and suggest that the cytokine-induced increase in Trx80 cell release may constitute a link between inflammation and the immune system in RA.

Secretory phospholipase A(2) activity and release kinetics of vascular tissue remodelling biomarkers after coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) has long been recognised as a main cause of a postoperative complex systemic inflammatory response after coronary artery bypass grafting (CABG). METHODS: We determined the kinetics of peripheral blood release of the novel inflammatory biomarkers secretory phospholipase A(2) (sPLA(2)), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) during the first 6 days following surgery in 16 patients undergoing CABG with (on-pump, n=9) or without (off-pump, n=7) CPB. Kinetic curves for these markers were compared to those of the well-known inflammatory parameters C-reactive protein (CRP) and fibrinogen. RESULTS: sPLA(2) activity exhibited a maximum value on day 2, then decreased until day 6 for both groups and in a similar manner as CRP levels. On the other hand, elevation of plasma levels of both MMP-9 and TIMP-1 occurred as early as on day 1 and remained at this level until day 6. No significant difference in kinetic characteristics (peak value, area under the curve, initial slope) between CABG with and without CPB was observed. CONCLUSIONS: These data show that the off- and on-pump groups did not show significantly different kinetics for the releases of all biomarkers studied, including sPLA(2) and biomarkers of the MMP-TIMP network. The off-pump procedure may therefore lead to global surgical trauma as important as CPB in terms of the systemic inflammatory process and matrix proteolysis pathway activation.

Release of brain natriuretic-related peptides (BNP, NT-proBNP) and cardiac troponins (cTnT, cTnI) in on-pump and off-pump coronary artery bypass surgery.

BACKGROUND: We studied the kinetic release of cardiac troponins (cTnI and cTnT) and B-type natriuretic peptides (BNP and NT-proBNP) in patients undergoing off-pump or on-pump coronary artery bypass surgery. METHODS: Twenty-five consecutive patients were prospectively enrolled. The patients were divided into three groups: beating heart (I), and cardiopulmonary bypass (CPB) with warm (II) or cold cardioplegia (III). Plasma samples were obtained before anesthesia induction until the sixth day after surgery. RESULTS AND CONCLUSIONS: The data were analyzed first for off-pump versus the CPB procedures and second for warm versus cold cardioplegia. The plasma troponin releases appeared to be significantly higher in the CPB groups in comparison to the beating heart group (P < 0.001 and P < 0.002 for cTnI and cTnT peak values, respectively). The peak of the B-type natriuretic peptide release appeared to be more delayed in the groups undergoing CPB than in the beating heart group (day 6 versus days 2 and 4 for NT-proBNP and BNP, respectively). Taken together, our results indicated that the new generation of cTnT assays seemed to be more sensitive than the cTnI assays for the diagnosis of myocardium injury. A lower increase in the cTnT values in the warm cardioplegic group indicated less damage of the myocardium than with cold cardioplegia. Our data also confirm better preservation of the myocardium with off-pump cardiac surgery than with CPB.