14 results on '"Longrois D"'
Search Results
2. Serum troponin Ic values in organ donors are related to donor myocardial dysfunction but not to graft dysfunction or rejection in the recipients.
- Author
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Boccheciampe N, Audibert G, Rangeard O, Charpentier C, Perrier JF, Lalot JM, Voltz C, Strub P, Loos-Ayav C, Meistelman C, Mertes PM, and Longrois D
- Subjects
- Adolescent, Adult, Biomarkers blood, Child, Graft Rejection physiopathology, Humans, Middle Aged, Patient Selection, Prognosis, Retrospective Studies, Time Factors, Graft Rejection blood, Heart Transplantation, Myocardium metabolism, Tissue Donors, Troponin I blood
- Abstract
Background: Increased plasma cardiac troponin I (cTnI) values in heart donors are associated with donor myocardial dysfunction and increased risk of rejection in the recipients. We investigated the association between cTnI values and myocardial dysfunction in potential heart donors and the relationship between donors' cTnI values and recipients' early myocardial function and 1 year survival and risk of rejection., Methods: cTnI was measured in 159 consecutive potential heart donors. Myocardial function was estimated by the left ventricular ejection fraction (LVEF) and segmental wall motion abnormalities (SWMA). Results are mean+/-SD (range) or median (interquartile range)., Results: cTnI values in potential donors were 2.1+/-5 ng/ml (0-40.4 ng/ml); cTnI values were significantly (P<0.001) higher: 4.2+/-5.9 ng/ml (0-30.6 ng/ml) for potential donors with LVEF <50% versus LVEF >50%: 1.7+/-4.7 ng/ml (0-40.4 ng/ml). cTnI values were significantly lower for donors without SWMA. cTnI values were significantly (P<0.001) lower for the 90 donors whose hearts were harvested: 1.1+/-2.3 ng/ml (0-15.6 ng/ml) versus the not harvested: 3.6+/-6.9 ng/ml (0-40.4 ng/ml). There were 87 recipients followed for 1 year. Donors' cTnI values were not associated with early alteration of LVEF, incidence of rejection or 1 year recipients' survival., Conclusion: Increased cTnI values in potential heart donors are statistically associated with myocardial dysfunction and could be helpful for organ selection. In contrast, cTnI values in heart donors were not associated with graft dysfunction or recipient survival after transplantation.
- Published
- 2009
- Full Text
- View/download PDF
3. (201)Tl and (99m)Tc-MIBI retention in an isolated heart model of low-flow ischemia and stunning: evidence of negligible impact of myocyte metabolism on tracer kinetics.
- Author
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Ayalew A, Marie PY, Menu P, Mertes PM, Audonnet S, Jouan V, Olivier P, Karcher G, Ungureanu-Longrois D, and Bertrand A
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- Animals, Blood Flow Velocity, Blood Pressure, Coronary Circulation, In Vitro Techniques, Microdialysis, Myocardial Ischemia metabolism, Myocardial Stunning metabolism, Oxygen Consumption, Rabbits, Radionuclide Imaging, Myocardial Ischemia diagnostic imaging, Myocardial Stunning diagnostic imaging, Myocardium metabolism, Radiopharmaceuticals pharmacokinetics, Technetium Tc 99m Sestamibi pharmacokinetics, Thallium Radioisotopes pharmacokinetics
- Abstract
Unlabelled: It is not known whether cellular metabolic disorders play a role in the decreased tracer uptake that is documented by conventional SPECT during low-flow ischemia or stunning. This study sought to determine the impact of low-flow ischemia and stunning on the kinetics of (201)Tl and MIBI across the plasma membrane of myocytes., Methods: The global myocardial retention (Rf) of (201)Tl and MIBI was determined in isolated working hearts from rabbits, perfused with red blood cell-enhanced solution. Experiments were performed in normoxia, with physiological values of coronary flow (N; n = 16); in low-flow ischemia, with a >50% reduction of coronary flow and a > or =20-mm Hg fall in systolic left ventricle pressure (L; n = 15); and in stunning, with 15 min of acute ischemia followed by reperfusion (S; n = 15). Concentration ratios across the plasma membrane of myocytes were also determined for both tracers and expressed as Ci/Cc, where Ci is interstitial activity determined with microdialysis, and Cc is activity from cellular space determined from Rf and Ci values., Results: There was a slight increase in average values of Ci/Cc in ischemia, but not in stunning, for (201)Tl (L, 0.011 +/- 0.006 vs. N, 0.006 +/- 0.004 [P < 0.05]; S, 0.007 +/- 0.004 vs. N [not significant]) and for MIBI (L, 0.011 +/- 0.008 vs. N, 0.005 +/- 0.004 [P < 0.05]; S, 0.005 +/- 0.003 vs. N [not significant]). Moreover, ischemia and stunning had no deleterious effects on the average values of global myocardial retention for (201)Tl (L, 0.63 +/- 0.09 vs. N, 0.50 +/- 0.14 [P < 0.05]; S, 0.59 +/- 0.10 vs. N [P < 0.05]) or for MIBI (L, 0.45 +/- 0.10 vs. N, 0.31 +/- 0.09 [P < 0.05]; S, 0.41 +/- 0.12 vs. N [P < 0.05]). In fact, these values were significantly enhanced in the 2 situations., Conclusion: The kinetics of (201)Tl and MIBI across the plasma membrane of myocytes were affected only poorly by low-flow ischemia and not at all by stunning, without any deleterious effects on myocardial retention of both tracers. During low-flow ischemia or stunning, therefore, the information provided by (201)Tl or MIBI SPECT is expected to depend on myocardial perfusion but not on cellular metabolic disorders.
- Published
- 2002
4. Activation of cardiac endothelium as a compensatory component in endotoxin-induced cardiomyopathy: role of endothelin, prostaglandins, and nitric oxide.
- Author
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Mebazaa A, De Keulenaer GW, Paqueron X, Andries LJ, Ratajczak P, Lanone S, Frelin C, Longrois D, Payen D, Brutsaert DL, and Sys SU
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- Animals, Arginine pharmacology, Binding, Competitive, Cardiomyopathies etiology, Cardiomyopathies physiopathology, Cyclooxygenase 2, Dose-Response Relationship, Drug, Endothelin-1 blood, Endothelin-1 pharmacology, Endothelins physiology, Endothelium, Vascular metabolism, Enzyme Inhibitors pharmacology, Hemodynamics, Immunohistochemistry, Isoenzymes drug effects, Isoenzymes metabolism, Male, Muscle Contraction drug effects, Myocardial Contraction drug effects, Nitric Oxide physiology, Nitric Oxide Synthase drug effects, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type II, Papillary Muscles drug effects, Papillary Muscles physiology, Prostaglandin-Endoperoxide Synthases drug effects, Prostaglandin-Endoperoxide Synthases metabolism, Prostaglandins physiology, Rabbits, Receptor, Endothelin A, Receptors, Endothelin metabolism, Superoxide Dismutase pharmacology, Time Factors, omega-N-Methylarginine pharmacology, Cardiomyopathies metabolism, Endothelium, Vascular drug effects, Lipopolysaccharides administration & dosage, Myocardium metabolism
- Abstract
Background: In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits., Methods and Results: Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPS+12h); staining for both isoforms was much weaker 24 hours later (LPS+36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPS+12h group, however, isometric twitches were significantly prolonged (482+/-14 versus 420+/-14 ms in the saline-treated group, P<0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPS+12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (P<0.01)., Conclusions: Cardiac endothelial activation and myocardial sensitization to endothelium-derived mediators may be part of an adaptive response in the early (12 hours) stages of septic cardiomyopathy.
- Published
- 2001
- Full Text
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5. Consequences of inspired oxygen fraction manipulation on myocardial oxygen pressure, adenosine and lactate concentrations: a combined myocardial microdialysis and sensitive oxygen electrode study in pigs.
- Author
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Siaghy EM, Devaux Y, Sfaksi N, Carteaux JP, Ungureanu-Longrois D, Zannad F, Villemot JP, Burlet C, and Mertes PM
- Subjects
- Animals, Blood Gas Analysis, Electrodes, Glucose metabolism, Hemodynamics, Microdialysis, Swine, Adenosine metabolism, Lactates metabolism, Myocardium metabolism, Oxygen metabolism
- Abstract
Adenosine is a potent vasodilator whose concentration has been shown to increase in cardiac tissue in response to hypoxia. However, the time-dependent relationship between the levels of myocardial interstitial adenosine and tissue oxygenation has not yet been completely established. Therefore, the purpose of this study was to investigate the complex relationship between tissue myocardial oxygen tension (PtiO(2)) and interstitial myocardial adenosine and lactate concentrations by developing a new technique which combines a cardiac microdialysis probe and a Clark-type P O(2)electrode. The combined and the single microdialysis probes were implanted in the left ventricular myocardium of anesthetized pigs. The consequences of the combined use of microdialysis and P O(2)probes on myocardial PtiO(2)and microdialysis performances against glucose were evaluated. A moderate but significant reduction in the relative recovery against glucose of the combined probe was observed when compared to that of the single microdialysis probe (42+/-2 v 32+/-1%, mean+/-S.E. M.n=5 P<0.05), at 2microl/min microdialysis probe perfusion flow. Similarly, myocardial oxygen enrichment, measured by the P O(2)electrode, was negligible when microdialysis probe perfusion flow was 2microl/min. Systemic hypoxia (FiO(2)=0.08) resulted in a significant decrease in PtiO(2)from 30+/-4 to 11+/-2 mmHg, limited increase in coronary blood flow (CBF), and a significant increase in myocardial adenosine and lactate concentrations from 0.34+/-0.05 to 0.98+/-0.06micromol/l and from 0.45+/-0.05 to 0.97+/-0.06 mmol/l respectively (P<0.05). Increasing the FiO(2)to 0.3 restored the PtiO(2)and hemodynamic parameters to baseline values with no changes in interstitial adenosine and lactate concentrations. Nevertheless, myocardial interstitial adenosine remained significantly higher than baseline values. In conclusion, this study demonstrates the ability of a combined probe to measure simultaneously regional myocardial PtiO(2)and metabolite concentration during hypoxia. The hypoxia-induced increase in myocardial adenosine persists after correction of hypoxia. The physiological significance of this observation requires further studies., (Copyright 2000 Academic Press.)
- Published
- 2000
- Full Text
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6. Consequences of labetalol administration on myocardial beta adrenergic receptors in the brain dead pig.
- Author
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Seguin C, Devaux Y, Aubert N, Siaghy EM, Zannad F, Burlet C, Ungureanu-Longrois D, and Mertes PM
- Subjects
- Adrenergic alpha-Antagonists pharmacology, Adrenergic beta-Antagonists pharmacology, Animals, Brain Death physiopathology, Heart drug effects, Hemodynamics drug effects, In Vitro Techniques, Kinetics, Pindolol metabolism, Swine, Brain Death metabolism, Labetalol administration & dosage, Myocardium metabolism, Pindolol analogs & derivatives, Receptors, Adrenergic, beta drug effects
- Abstract
Objectives: Cardiac dysfunction following brain death is associated with highly increased myocardial norepinephrine, lactate and adenosine concentrations. Administration of labetalol, a mixed alpha-, beta-adrenergic receptor antagonist, attenuates metabolic disturbances and improves myocardial function. The purpose of this study was to investigate beta-adrenergic receptor (beta AR) density and affinity in the presence or absence of labetalol administration, as a possible mechanism of the protective effects of this drug., Methods: Experimental animals were divided into three groups: sham-operated, brain-dead pigs, and brain-dead pigs treated with labetalol (10 +/- 3 mg/kg). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of beta AR were determined with (-)-[125I]cyanopindolol on myocardial samples harvested 3 hours after brain death., Results: Left ventricular beta AR density and affinity were identical in brain-dead and sham-operated animals. Labetalol-treated pigs exhibited a significant decrease of Bmax and an increase of Kd as compared with brain-dead pigs. Bmax decrease was due to the persistence of labetalol in the membrane preparations. Increased Kd was too low to be biologically significant. Therefore, beta AR number and affinity can be considered as unchanged after adrenergic blockade with labetalol., Conclusions: The protective mechanism of labetalol on brain death-induced myocardial dysfunction cannot be explained by changes in beta AR density and affinity but is probably related to a preservation of the oxygen consumption/oxygen delivery balance during the autonomic storm.
- Published
- 2000
7. Increase in myocardial interstitial adenosine and net lactate production in brain-dead pigs: an in vivo microdialysis study.
- Author
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Halejcio-Delophont P, Siaghy EM, Devaux Y, Ungureanu-Longrois D, Richoux JP, Beck B, Burlet C, Villemot JP, and Mertes PM
- Subjects
- Animals, Blood Gas Analysis, Brain Death physiopathology, Hemodynamics, Lactic Acid blood, Microdialysis, Swine, Time Factors, Adenosine metabolism, Brain Death metabolism, Lactic Acid metabolism, Myocardium metabolism
- Abstract
Background: Brain death-related cardiovascular dysfunction has been documented; however, its mechanisms remain poorly understood. We investigated changes in myocardial function and metabolism in brain-dead and control pigs., Methods: Heart rate, systolic (SAP) and mean (MAP) arterial pressure, left ventricular (LV) dP/dtmax, rate-pressure product, cardiac output (CO), left anterior descending coronary artery blood flow, lactate metabolism, and interstitial myocardial purine metabolite concentrations, monitored by cardiac microdialysis, were studied. A volume expansion protocol was performed at the end of the study., Results: After brain death, a transient increase in heart rate (from 90 [67-120] to 158 [120-200] beats/min) (median, with range in brackets), MAP (82 [74-103] to 117 [85-142] mmHg), LV dP/dtmax (1750 [1100-2100] to 5150 [4000-62,000] mmHg x sec(-1), rate-pressure product (9100 [7700-9700] beats mmHg/min to 22,750 [20,000-26,000] beats mmHg/min), CO (2.2 [2.0-4.0] to 3.3 [3.0-6.0] L/min), and a limited increase in left anterior descending coronary artery blood flow (40 [30-60] to 72 [50-85] ml/min) were observed. Net myocardial lactate production occurred (27 [4-40] to -22 [-28, -11] mg/L, P<0.05) and persisted for 2 hr. A 6-7-fold increase in adenosine dialysate concentration was observed after brain death induction (2.9 [1.0-5.8] to 15.8 [7.0-50.7] micromol/L), followed by a slow decline. Volume expansion significantly increased MAP, CO, and LV dP/dtmax in control animals, but decreased LV dP/dtmax and slightly increased CO in brain-dead animals. A significant increase in adenosine concentration was observed in both groups, with higher levels (P<0.05) in brain-dead animals., Conclusions: Brain death increased oxygen demand in the presence of a limited increase in coronary blood flow, resulting in net myocardial lactate production and increased interstitial adenosine concentration consistent with an imbalance between myocardial oxygen demand and supply. This may have contributed to the early impairment of cardiac function in brain-dead animals revealed by rapid volume infusion.
- Published
- 1998
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8. Consequences of brain death on coronary blood flow and myocardial metabolism.
- Author
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Halejcio-Delophont P, Siaghy EM, Devaux Y, Richoux JP, Bischoff N, Carteaux JP, Ungureanu-Longrois D, Burlet C, Villemot JP, and Mertes PM
- Subjects
- Adenosine metabolism, Analysis of Variance, Animals, Blood Pressure, Brain Death metabolism, Heart Rate, Swine, Time Factors, Ventricular Function, Left, Brain Death physiopathology, Coronary Circulation physiology, Myocardium metabolism
- Published
- 1998
- Full Text
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9. Regulation of bFGF expression and ANG II secretion in cardiac myocytes and microvascular endothelial cells.
- Author
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Fischer TA, Ungureanu-Longrois D, Singh K, de Zengotita J, DeUgarte D, Alali A, Gadbut AP, Lee MA, Balligand JL, Kifor I, Smith TW, and Kelly RA
- Subjects
- Angiotensin II pharmacology, Animals, Cells, Cultured, Endothelin-1 pharmacology, Endothelium, Vascular cytology, Fibroblast Growth Factor 2 genetics, Fibroblast Growth Factor 2 pharmacology, Heart Ventricles, Microcirculation, Myocardium cytology, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Angiotensin II metabolism, Coronary Circulation, Endothelium, Vascular metabolism, Fibroblast Growth Factor 2 metabolism, Myocardium metabolism
- Abstract
Basic fibroblast growth factor (bFGF; fibroblast growth factor-2) and angiotensin II (ANG II), among other peptide signaling autacoids (cytokines), are known to regulate the phenotypic adaptation of cardiac muscle to physiological stress. The cell type(s) in cardiac muscle responsible for ANG II synthesis and secretion and the role of endogenous cytokines in the regulation of bFGF induction remain unclear. With the use of confluent, serum-starved, low-passage cultures of cardiac microvascular endothelial cells (CMEC), ANG II could be detected in cellular lysates and in medium conditioned by these cells with the use of high-performance liquid chromatography followed by radioimmunoassay. The secretion of angiotensins by individual CMEC could be detected with a cell-blot assay technique. ANG II secretion was decreased by brefeldin A, an agent that interrupts constitutive and regulated secretory pathways for peptide autacoid/ hormone synthesis, suggesting de novo synthesis, activation, and secretion of angiotensins by CMEC. In primary isolates of adult rat ventricular myocytes (ARVM) and CMEC, ANG II, acting at ANG II type 1 receptors in both cell types, was found to increase bFGF mRNA levels measured by ribonuclease protection assay. Endothelin-1 (ET-1), which is known to be synthesized by CMEC, and bFGF itself, which has been detected in both ARVM and CMEC, increased bFGF transcript levels in both cell types. Interleukin-1beta (IL-1beta), which like ANG II and ET-1 is known to activate mitogen-activated protein kinases in both ARVM and CMEC, increased bFGF mRNA levels only in cardiac myocytes. Thus cytokines such as ANG II, ET-1, bFGF, and IL-1beta locally generated by cellular constituents of cardiac muscle, including CMEC, regulate bFGF mRNA levels in a cell type-specific manner.
- Published
- 1997
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10. Induction of nitric oxide synthase activity by cytokines in ventricular myocytes is necessary but not sufficient to decrease contractile responsiveness to beta-adrenergic agonists.
- Author
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Ungureanu-Longrois D, Balligand JL, Simmons WW, Okada I, Kobzik L, Lowenstein CJ, Kunkel SL, Michel T, Kelly RA, and Smith TW
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- Animals, Insulin pharmacology, Interferon-gamma pharmacology, Interleukin 1 Receptor Antagonist Protein, Lipopolysaccharides pharmacology, Macrophages physiology, Male, Nitric Oxide Synthase, Rats, Rats, Sprague-Dawley, Sialoglycoproteins pharmacology, Tumor Necrosis Factor-alpha pharmacology, Adrenergic beta-Agonists pharmacology, Amino Acid Oxidoreductases biosynthesis, Cytokines pharmacology, Myocardial Contraction drug effects, Myocardium enzymology
- Abstract
Recent evidence has documented that increased activity of an inducible nitric oxide synthase (iNOS; type 2 NO synthase) in primary isolates of adult rat ventricular myocytes after exposure to soluble mediators in medium conditioned by lipopolysaccharide-activated macrophages is associated with a decrease in their contractile responsiveness to beta-adrenergic agonists. It remained unclear which specific inflammatory cytokines in this medium contribute to the induction of iNOS activity in myocytes and whether induction of iNOS would result in an obligatory decline in contractile function. Interleukin (IL)-1 beta and tumor necrosis factor-alpha (TNF-alpha) were both present in the lipopolysaccharide-activated macrophage-conditioned medium. However, only IL-1 receptor antagonist and not an anti-rat TNF-alpha antiserum diminished the extent of iNOS induction in myocytes exposed to this medium and prevented a decline in contractile responsiveness to isoproterenol. When recombinant cytokines were used, IL-1 beta, TNF-alpha, and IFN-gamma each induced iNOS activity in cardiac myocytes at 24 hours. However, only the combination of IL-1 beta and IFN-gamma reproducibly caused contractile dysfunction in cardiac myocytes. Among the constituents of the defined medium routinely used for maintenance of adult rat ventricular myocytes in primary culture, it was noted that insulin (10(-7) mol/L) was required for NO production, as detected by nitrite release in cytokine-pretreated myocytes, although insulin had no effect on the extent of induction of iNOS mRNA or maximal enzyme activity in myocyte cell lysates.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
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11. Induction of NO synthase in rat cardiac microvascular endothelial cells by IL-1 beta and IFN-gamma.
- Author
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Balligand JL, Ungureanu-Longrois D, Simmons WW, Kobzik L, Lowenstein CJ, Lamas S, Kelly RA, Smith TW, and Michel T
- Subjects
- Amino Acid Oxidoreductases genetics, Animals, Base Sequence, Cells, Cultured, Cloning, Molecular, DNA, Complementary genetics, Endothelium, Vascular drug effects, Endothelium, Vascular enzymology, Enzyme Induction drug effects, Immunohistochemistry, Mice, Microcirculation drug effects, Microcirculation enzymology, Molecular Sequence Data, Nitric Oxide Synthase, Polymerase Chain Reaction, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Amino Acid Oxidoreductases biosynthesis, Interferon-gamma pharmacology, Interleukin-1 pharmacology, Myocardium enzymology
- Abstract
There are important phenotypic differences between endothelial cells of large vessels and the microvasculature and among microvascular endothelial cells isolated from different tissues and organs. In contrast to most macrovascular endothelial cells, we demonstrate that cultured cardiac microvascular endothelial cells (CMEC) have no detectable constitutive NO synthase (NOS) activity but have a robust increase in NOS activity in response to specific inflammatory cytokines. To determine the identity of the inducible NOS (iNOS) isoform(s) induced by cytokines, we used reverse-transcription polymerase chain reaction techniques to clone and sequence a 217-bp cDNA fragment from CMEC cultures pretreated with interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) that was identical to the corresponding portion of the murine macrophage iNOS cDNA. By use of this CMEC iNOS cDNA as a probe in Northern analyses, IL-1 beta, but not IFN-gamma, increased iNOS mRNA content in CMEC, although IFN-gamma markedly potentiated iNOS induction in these cells. In IL-1 beta- and IFN-gamma-pretreated CMEC, dexamethasone only minimally suppressed the rise in iNOS mRNA, protein abundance, or maximal iNOS enzyme activity in whole cell lysates but suppressed nitrite production by 60% in intact CMEC. Dual labeling of cytokine-pretreated CMEC in primary culture with an anti-iNOS antiserum and a fluorescein-labeled lectin specific for the microvascular endothelium of rat heart (GS-1) confirmed the presence of iNOS expression in these cells. iNOS was also detected in microvascular endothelium in situ in ventricular muscle from lipopolysaccharide-, but not sham-injected, rat hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
- Full Text
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12. Myocardial contractile dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes.
- Author
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Ungureanu-Longrois D, Balligand JL, Kelly RA, and Smith TW
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- Amino Acid Oxidoreductases biosynthesis, Animals, Enzyme Induction, Humans, Nitric Oxide Synthase, Signal Transduction, Systemic Inflammatory Response Syndrome enzymology, Amino Acid Oxidoreductases metabolism, Cytokines pharmacology, Cytokines physiology, Heart physiopathology, Myocardial Contraction drug effects, Myocardium enzymology, Systemic Inflammatory Response Syndrome physiopathology
- Abstract
A major determinant of survival in patients with advanced viral or bacterial infection, or following severe trauma or burns complicated by multiple organ failure, is the combination of clinical signs termed the systemic inflammatory response syndrome (SIRS). SIRS is characterized by hypotension, tachypnea, hypo- or hyperthermia and leukocytosis as well as other clinical signs and symptoms, including a depression in myocardial contractile function. Heart failure complicating systemic sepsis or other causes of SIRS is usually not accompanied by coronary artery ischemia due to hypotension, myocardial necrosis, or marked cardiac interstitial inflammatory infiltrates, and thus the cause of cardiac contractile dysfunction in this syndrome has remained unclear. However, recent evidence has implicated an endogenous nitric oxide (NO) signalling pathway within cardiac myocytes and other cellular constituents of cardiac muscle, including the microvascular endothelium, as a possible contributor to the pathogenesis of heart failure in this syndrome. Cardiac myocytes are now known to express both constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities. Activation of cNOS appears to modulate cardiac myocyte responsiveness to muscarinic cholinergic and beta-adrenergic receptor stimulation. Induction of iNOS by soluble inflammatory mediators, including cytokines, causes a marked depression in myocyte contractile responsiveness to beta-adrenergic agonists. Thus, inappropriate activation of cNOS or excessive or prolonged induction of iNOS in the myocardium may contribute to cardiac dysfunction complicating SIRS.
- Published
- 1995
- Full Text
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13. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro.
- Author
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Balligand JL, Ungureanu-Longrois D, Simmons WW, Pimental D, Malinski TA, Kapturczak M, Taha Z, Lowenstein CJ, Davidoff AJ, and Kelly RA
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cells, Cultured, Cloning, Molecular, Cytokines pharmacology, DNA Primers chemistry, Enzyme Induction, GTP Cyclohydrolase metabolism, Gene Expression drug effects, Glucocorticoids pharmacology, In Vitro Techniques, Lipopolysaccharides pharmacology, Male, Molecular Sequence Data, Myocardial Contraction, Nitric Oxide Synthase, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Amino Acid Oxidoreductases biosynthesis, Myocardium enzymology
- Abstract
Cellular constituents of heart muscle contain both constitutive and inducible nitric oxide (NO) signaling pathways that modulate the contractile properties of cardiac myocytes. The identities of the inducible NO synthase (iNOS) isoform(s) expressed in cardiac muscle, and of the specific cell types expressing iNOS activity, remain poorly characterized. We amplified a 217-base pair cDNA by reverse transcriptase-polymerase chain reaction from primary cultures of inflammatory cytokine-pretreated adult rat ventricular myocytes (ARVM) that was nearly identical to other iNOS cDNA sequences. Using this 217-base pair cDNA as a probe in Northern blots, we found no evidence of iNOS mRNA in control myocytes, but both interleukin-1 beta and interferon-gamma individually increased iNOS mRNA abundance in primary cultures of ARVM, with maximal expression at 12 h. The half-life of iNOS mRNA in actinomycin C1-treated cells was 4 h. Both dexamethasone and transforming growth factor-beta attenuated the induction of iNOS mRNA abundance and enzyme activity by IL-1 beta and INF gamma. Pretreatment with dexamethasone also abolished the induction of iNOS mRNA, but not the increase in GTP cyclohydrolase mRNA in purified cardiac myocytes from lipopolysaccharide-injected rats. In order to further characterize the specific cell type producing NO, we used a NO-specific porphyrinic/Nafion-coated microsensor to record NO release from a single, isolated ARVM pretreated with IL-1 beta and IFN gamma in L-arginine-depleted medium. NO release could be detected following microinjection of L-arginine in the vicinity of the cell juxtaposed to the NO microsensor, but not following microinjection of D-arginine, and not from ARVM pretreated with L-N-monomethylarginine. Cytokine-pretreated ARVM that had been maintained in L-arginine-depleted medium also exhibited a depressed contractile response to isoproterenol after addition of L-arginine, but not D-arginine. These results indicate that altered contractile function of cardiac myocytes following exposure to specific inflammatory cytokines is due to induction of myocyte iNOS.
- Published
- 1994
14. Consequences of labetalol administration on myocardial beta adrenergic receptors in the brain dead pig
- Author
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Seguin C, Devaux Y, Aubert N, Em, Siaghy, Zannad F, Burlet C, Ungureanu-Longrois D, and Pm, Mertes
- Subjects
Brain Death ,Kinetics ,Swine ,Myocardium ,Pindolol ,Adrenergic beta-Antagonists ,Receptors, Adrenergic, beta ,Hemodynamics ,Animals ,Heart ,Labetalol ,In Vitro Techniques ,Adrenergic alpha-Antagonists - Abstract
Cardiac dysfunction following brain death is associated with highly increased myocardial norepinephrine, lactate and adenosine concentrations. Administration of labetalol, a mixed alpha-, beta-adrenergic receptor antagonist, attenuates metabolic disturbances and improves myocardial function. The purpose of this study was to investigate beta-adrenergic receptor (beta AR) density and affinity in the presence or absence of labetalol administration, as a possible mechanism of the protective effects of this drug.Experimental animals were divided into three groups: sham-operated, brain-dead pigs, and brain-dead pigs treated with labetalol (10 +/- 3 mg/kg). The maximum number of binding sites (Bmax) and the dissociation constant (Kd) of beta AR were determined with (-)-[125I]cyanopindolol on myocardial samples harvested 3 hours after brain death.Left ventricular beta AR density and affinity were identical in brain-dead and sham-operated animals. Labetalol-treated pigs exhibited a significant decrease of Bmax and an increase of Kd as compared with brain-dead pigs. Bmax decrease was due to the persistence of labetalol in the membrane preparations. Increased Kd was too low to be biologically significant. Therefore, beta AR number and affinity can be considered as unchanged after adrenergic blockade with labetalol.The protective mechanism of labetalol on brain death-induced myocardial dysfunction cannot be explained by changes in beta AR density and affinity but is probably related to a preservation of the oxygen consumption/oxygen delivery balance during the autonomic storm.
- Published
- 2001
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