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Monique Bernard

Publications and source records attributed to Monique Bernard.

14 recordsLinked to original sources
PubMed2006

Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis.

OBJECTIVE: Dysregulation of the blood-brain barrier (BBB) and transendothelial migration of immune cells are among the earliest central nervous system changes partaking in lesion formation in both multiple sclerosis (MS) and its early clinical form, the clinically isolated syndrome. Evidence for the anti-inflammatory effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors within the central nervous system arose from studies demonstrating that statins improve clinical signs in the animal model of MS and reduce the number of gadolinium-enhancing lesions in MS. METHODS: We sought to describe the impact of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor treatment on the physiology and immunology of human BBB-derived endothelial cells (ECs). RESULTS: We demonstrate that lovastatin and simvastatin induce a 50 to 60% reduction in the diffusion rates of bovine serum albumin and [(14)C]-sucrose across human BBB-ECs in vitro through abrogation of isoprenylation processes, but independent of the expression of the tight junction molecules occludin, VE-cadherin, JAM-1, zonula occluden-1, and zonula occluden-2. Simvastatin and lovastatin were equipotent in reducing BBB permeability in vitro, with median effective concentration (EC(50)) of 9.5 x 10(-8) and 1.0 x 10(-7)M, respectively. We further demonstrate that lovastatin and simvastatin treatment of BBB-ECs significantly restricts the migration of clinically isolated syndrome-derived and MS-derived monocytes and lymphocytes across the human BBB in vitro, through a specific reduction in the secretion of the chemokines monocyte chemotactic protein-1/CCL2 and interferon-gamma-inducible protein-10/CXCL10 by BBB-ECs. INTERPRETATION: Our data parallel the previously reported magnetic resonance imaging-based radiological findings and suggest an effect of statins that could be beneficial in early MS, restricting the diffusion of molecular tracers and the migration of immune cells across the human BBB.

Adult↗
PubMed2005

Non-invasive diagnostic of cardiac allograft vasculopathy by 31P magnetic resonance chemical shift imaging.

BACKGROUND: Coronary angiography is still the gold standard for the diagnosis of cardiac allograft vasculopathy (CAV) for which alternative non-invasive diagnostic approaches are currently investigated. In this study, we assessed whether 31P magnetic resonance chemical shift imaging can diagnose CAV by studying variations in cardiac high-energy phosphates in a population of adult heart transplant recipients. METHODS AND RESULTS: CAV was defined by coronary angiography as the presence of diffuse coronary irregularities with significant concentric narrowing on epicardial or distal coronary arteries. Eight patients with CAV (group A), and 18 patients without CAV (group B) were included in this study and compared to nine healthy volunteers (group C). Patients and volunteers underwent 31P three-dimensional chemical shift imaging to determine the ratio of phosphocreatine (PCr) and adenosine tri-phosphate (ATP). PCr/ATP was significantly lower in group A (1.51+/-0.50) than in groups B and C (1.98+/-0.53 (p=0.003) and 2.14+/-0.31 (p=0.001)), respectively. Time from transplant, number of episodes of acute rejection, and left ventricular ejection fraction (LVEF) were not significantly different between patient groups. A PCr/ATP value of 1.59 was the optimal cut-off value to predict CAV (specificity and sensitivity of 100% and 72%, respectively). CONCLUSION: Clinically, in vivo 31P chemical shift imaging is a promising, non-invasive method to detect the potential modifications of high-energy phosphates related to CAV and to better screen indications for coronary angiograms. This may be relevant for coronary angiography follow-up and adjustments of immunotherapy regimen.

Adenosine Triphosphate↗
PubMed2005

Novel fibrogenic pathways are activated in response to endothelial apoptosis: implications in the pathophysiology of systemic sclerosis.

Apoptosis of endothelial cells (EC) is appreciated as a primary pathogenic event in systemic sclerosis. Yet, how apoptosis of EC leads to fibrosis remains to be determined. We report that apoptosis of EC triggers the release of novel fibrogenic mediators. Medium conditioned by apoptotic EC (SSC) was found to inhibit apoptosis of fibroblasts, whereas medium conditioned by EC in which apoptosis was blocked (with either pan-caspase inhibition or Bcl-x(L) overexpression) did not. PI3K was activated in fibroblasts exposed to SSC. This was associated with downstream repression of Bim-EL and long-term up-regulation of Bcl-x(L) protein levels. RNA interference for Bim-EL in fibroblasts blocked apoptosis. SSC also induced PI3K-dependent myofibroblast differentiation with expression of alpha-smooth muscle actin, formation of stress fibers, and production of collagen I. A C-terminal fragment of the domain V of perlecan was identified as one of the fibrogenic mediators present in SSC. A synthetic peptide containing an EGF motif present on the perlecan fragment and chondroitin 4-sulfate, a glycosaminoglycan anchored on the domain V of perlecan, induced PI3K-dependent resistance to apoptosis in fibroblasts and myofibroblast differentiation. Human fibroblasts derived from sclerodermic skin lesions were more sensitive to the antiapoptotic activities of the synthetic peptide and chondroitin 4-sulfate than fibroblasts derived from normal controls. Hence, we propose that a chronic increase in endothelial apoptosis and/or increased sensitivity of fibroblasts to mediators produced by apoptotic EC could form the basis of a fibrotic response characterized by sustained induction of an antiapoptotic phenotype in fibroblasts and persistent myofibroblast differentiation.

Adult↗
PubMed2005

In vivo assessment of myocardial blood flow in rat heart using magnetic resonance imaging: effect of anesthesia.

PURPOSE: To assess the influence of isoflurane and pentobarbital anesthesia and the carrier gases on myocardial blood flow (MBF) in the rat heart in vivo. MATERIALS AND METHODS: MBF was quantified in vivo using arterial spin-labeling (ASL) magnetic resonance imaging (MRI). Left ventricular (LV) function was estimated during the same experiment using cine-MRI. Thirty-four male Wistar-Kyoto rats were divided in four groups, one anesthetized with isoflurane in oxygen:nitrous oxide mix (ISO), the three others with intraperitoneal pentobarbital, and breathing either room air (PB), oxygen:nitrous oxide (PB + N(2)O), or oxygen:nitrogen (PB + N(2)). RESULTS: MBF was significantly higher in the ISO and PB + N(2)O groups vs. PB and in ISO vs. PB + N(2), with the following respective MBF values: ISO, 5.9 +/- 1.1; PB, 4.0 +/- 0.8; PB + N(2)O, 5.1 +/- 1.4; and PB + N(2), 4.6 +/- 0.8 mL/g/minute, mean +/- SD. Ejection fractions were reduced by 10% in PB and PB + N(2)O rats vs. ISO rats. Cardiac output (CO) and index (CI) were 25 to 30% lower in all rats anesthetized with pentobarbital than with isoflurane. CONCLUSION: Isoflurane and nitrous oxide induce a higher MBF than pentobarbital. Isoflurane also induces a higher ejection fraction in healthy rats.

Anesthesia, Inhalation↗
PubMed2005

Myocardial blood flow mapping in mice using high-resolution spin labeling magnetic resonance imaging: influence of ketamine/xylazine and isoflurane anesthesia.

Genetically modified mouse models of many human diseases reflecting cardiovascular alterations are currently available. To date, little information on absolute myocardial perfusion in mice is found in the literature. High-resolution quantitative myocardial blood flow maps (in-plane resolution 156 x 312 mum(2), slice thickness 1.5 mm) have been obtained noninvasively within 25 min at 4.7 T in 30 freely breathing C57/Bl6J mice using electrocardiogram- and respiration-gated spin labeling magnetic resonance imaging (MRI). Regional myocardial blood flow measurements were carried out, and the effects of isoflurane at two different concentrations and ketamine/xylazine anesthesia were assessed. The mean blood flow value in the left ventricular myocardium was 6.0 +/- 1.9 mL g(-1) min(-1) under ketamine/xylazine and 6.9 +/- 1.7 mL g(-1) min(-1) (group average +/- SD) under isoflurane (1.25%). Under the influence of higher isoflurane concentration (2.00%), myocardial blood flow increased dramatically to 16.9 +/- 1.8 mL g(-1)min(-1) with no significant change in heart rate. This work illustrates the feasibility of noninvasive quantitative myocardial perfusion mapping in mice using MRI. The study of the influence of anesthesia shows that myocardial blood flow is highly sensitive to isoflurane concentration. The method employed offers a noninvasive approach to longitudinal studies of murine models of cardiac disease.

Adrenergic alpha-Agonists↗
PubMed2005

31P MRS of heart grafts provides metabolic markers of early dysfunction.

OBJECTIVE: Early graft failure (EGF) is a life-threatening event still accounting for a significant percentage of early deaths after heart transplantation. We tested whether selected metabolic markers, including high-energy phosphate concentrations measured ex vivo in pre-transplant heart grafts by (31)P magnetic resonance spectroscopy (MRS) are related with early post-transplant outcome. METHODS: During a 3-year period, 26 heart grafts harvested in the vicinity of the transplantation centre were studied. Evaluation of transplantability was done conventionally. (31)P MRS was performed ex vivo approximately 60min after aortic cross-clamp to quantify ATP, P(i) and PCr concentration ratios. A MRS-score was defined as a combination of intracellular pH (pHi) and the PCr/P(i) ratio. EGF was defined as the need to abnormally extend circulatory support or to use more than two inotropes before weaning the patient from CPB after transplantation. The grafts were attributed to three groups as follows: A1, transplanted with uneventful outcome (n=14); A2, transplanted with subsequent EGF (n=3) and B, not suitable for transplantation (n=9). RESULTS: Significant differences between groups existed for the following metabolic markers: PCr/ATP (P=0.013), PCr/P(i) (P=0.0004), pHi (P=0.0016) and MRS-score (P=0.0001). The sensitivity, specificity and positive likelihood ratio for EGF with a MRS-score<or=1.95 were, respectively, 100%, 86% and 7. CONCLUSIONS: In the setting of this study, post-transplant outcome was related to the pre-transplant MRS-score of grafts evaluated ex vivo. This result might help to more securely use grafts from marginal donors.

Adenosine Triphosphate↗
PubMed2005

Noninvasive characterization of myocardial blood flow in diabetic, hypertensive, and diabetic-hypertensive rats using spin-labeling MRI.

OBJECTIVE: Microvascular alterations in the diabetic and hypertensive heart are likely to contribute to heart failure. In this work, myocardial blood flow and left ventricular function were measured in vivo in diabetic, hypertensive, and diabetic-hypertensive rats using MRI methods. METHODS: An 8-week-duration type 1 diabetes was induced by streptozotocin (STZ) in 8 Wistar-Kyoto (WKY) rats (STZ) and in 11 spontaneously hypertensive (SHR) rats (STZ-SHR). Fourteen WKY and 12 SHR served as control and hypertensive groups. Myocardial blood flow quantification was performed using an arterial spin-labeling MRI method. Left ventricular morphology and function were assessed during the same experiment using cine-MRI. RESULTS: Respective myocardial blood flow values for each group were 6.4 +/- 1.1 (WKY), 6.0 +/- 1.9 (STZ), 5.5 +/- 1.3 (SHR), and 4.3 +/- 0.9 mL. g(-1). min(-1) (STZ-SHR). Myocardial blood flow was significantly decreased in STZ-SHR rats compared with the other groups (p <.05, STZ-SHR vs. all groups). Cine-MRI showed morphological alterations in all pathological groups. No alteration of the ejection fraction was observed in the pathological groups. CONCLUSION: Myocardial blood flow is altered in vivo before any sign of heart failure when rats have type 1 diabetes and hypertension simultaneously. When only one of the pathologies occurs, MBF does not vary significantly.

Animals↗
PubMed2005

Defective myocardial blood flow and altered function of the left ventricle in type 2 diabetic rats: a noninvasive in vivo study using perfusion and cine magnetic resonance imaging.

OBJECTIVE: In type 2 diabetes mellitus, cardiovascular complications are related to microvascular abnormalities. In this work, we aimed at characterizing in vivo myocardial blood flow and left ventricular function of the Goto-Kakizaki (GK) rat as a nonobese model of type 2 diabetes. MATERIALS AND METHODS: We performed arterial spin labeling magnetic resonance imaging (MRI) for myocardial blood flow quantification and cine MRI for functional evaluation in free-breathing isoflurane-anesthetized animals. RESULTS: Myocardial blood flow was altered in adult female GK rats compared with age-matched female Wistar rats (4.7 +/- 1.6 vs. 7.1 +/- 1.2 mL/g/min respectively, P = 0.0022). Ejection fraction was decreased in GK compared with Wistar rats (64 +/- 7 vs. 78 +/- 8% respectively, P <0.005), mainly as a result of a loss in left ventricular longitudinal contraction. CONCLUSIONS: Adult female GK rats have defective myocardial blood flow associated with altered left ventricular function. This multiparametric MRI approach in the GK rat is of particular interest for the study of type 2 diabetic cardiomyopathy.

Animals↗
PubMed2004

High-resolution myocardial perfusion mapping in small animals in vivo by spin-labeling gradient-echo imaging.

An ECG and respiration-gated spin-labeling gradient-echo imaging technique is proposed for the quantitative and completely noninvasive measurement and mapping of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH imaging, the spatial resolution of the perfusion maps is not limited by the heart rate. A significant improvement in image quality is achieved by synchronizing the inversion pulse to the respiration movements of the animals, thereby allowing for spontaneous respiration. High-resolution myocardial perfusion maps (in-plane resolution=234 x 468 microm2) demonstrating the quality of the perfusion measurement were obtained at 4.7 T in a group of seven freely breathing Wistar-Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average +/- SD) was 5.5 +/- 0.7 ml g(-1)min(-1). In four animals, myocardial perfusion was mapped and measured under cardiac dobutamine stress. Perfusion increased to 11.1 +/- 1.9 ml g(-1)min(-1). The proposed method is particularly useful for the study of small rodents at high fields.

Animals↗
PubMed2003

NOS substrate during cardioplegic arrest and cold storage decreases stunning after heart transplantation in a rat model.

BACKGROUND: In this study, we evaluated how adding L-arginine to Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution affected myocardial performance during post-ischemic in vivo reperfusion. METHODS: Experiments were conducted using a modified Lewis-Lewis heterotopic heart transplantation model, with a total ischemic time of 3 hours followed by 1 or 24 hours of blood reperfusion. Heart grafts were arrested using intra-aortic injection of CRMBM solution, either supplemented or not supplemented with 2 mmol/liter L-arginine (n = 12 in each group). We measured systolic indexes and simultaneously performed phosphorus magnetic resonance spectroscopy ((31)P MRS). We quantified total endothelial nitric oxide synthase (eNOS) protein using the Western blot test of freeze-clamped hearts. RESULTS: Contractility during early reperfusion was significantly better in grafts arrested with CRMBM solution enriched with L-arginine: mean rate pressure product, 11249 +/- 1548 vs 5637 +/- 1118 mm Hg/min (p = 0.05), and maximal first derivative of the pressure signal (dP/dt(max)), 1721 +/- 177 vs 1214 +/- 321 mm Hg/sec (p = 0.013). Conversely, during late reperfusion, contractility did not relate to the nature of the preservation solution. The presence of L-arginine in the CRMBM solution did not alter time-related variations of high-energy phosphate ratios measured using in vivo (31)P MRS. The eNOS protein level decreased significantly during early compared with late reperfusion, with no effect caused by L-arginine. CONCLUSIONS: During early reperfusion, the limited myocardial stunning observed with CRMBM solution containing L-arginine does not relate to energy metabolism but to better preservation of the NO pathway.

Allopurinol↗
PubMed2003

Different pathways for sodium entry in cardiac cells during ischemia and early reperfusion.

A number of data are consistent with the hypothesis that increases in intracellular Na+ concentration (Na+i) during ischemia and early reperfusion lead to calcium overload and exacerbation of myocardial injury. However, the mechanisms underlying the increased Na+i remain unclear. 23Na nuclear magnetic resonance spectroscopy was used to monitor Na+i in isolated rat hearts perfused with a high concentration of fatty acid as can occur under some pathological conditions. Whole-cell patch-clamp experiments were also performed on isolated cardiomyocytes in order to investigate the role of voltage-gated sodium channels. Na+i increased to substantially above control levels during no-flow ischemia. The results show that a pharmacological reduction of Na+i increase by cariporide (1 micromol/L, a Na+/H+ exchange blocker) is not the only protection against ischemia-reperfusion damage, but that such protection may also be brought about by metabolic action aimed at reducing fatty acid utilization by myocardial cells. This action was obtained in the presence of etomoxir (0.1 micromol/L), an inhibitor of carnitine palmitoyltransferase-1 (the key enzyme involved in fatty acid uptake by the mitochondria) which also decreases long-chain acyl carnitine accumulation. The possibility of Na+ channels participating in Na+i increase as a consequence of alterations in cardiac metabolism was studied in isolated cells. Sustained I(Na) was stimulated by the presence of lysophosphatidylcholine (LPC, 10 micromol/L) whose accumulation during ischemia is, at least partly, dependent on increased long-chain acyl carnitine. Current activation was particularly significant in the range of potentials between -60 and -20 mV. This may have particular relevance in ischemia. The quantity of charge carried by sustained I(Na) was reduced by 24% in the presence of 1 micromol/L cariporide. Therefore, limitation of long-chain fatty acid metabolism, and consequent limitation of ischemia-induced long-chain acyl carnitine accumulation, may contribute to reducing intracellular Na+ increase during ischemia-reperfusion.

Animals↗
PubMed2002

Objective and noninvasive metabolic characterization of donor hearts by phosphorous-31 magnetic resonance spectroscopy.

OBJECTIVE: The authors performed a multi-institutional, prospective, blind study on hearts from local donors to validate the feasibility and accuracy of the metabolic evaluation of human hearts by phosphorus-31 ( P) magnetic resonance spectroscopy (MRS) before transplantation. METHODS: Twenty-one hearts were separated into two groups according to a transplantation score (TS) on the basis of the current clinical and echocardiographic evaluation as follows: TS1 (n=7), grafts for United Network for Organ Sharing (UNOS) 1 patients only; and TS2 (n=14), grafts suitable for UNOS 2 patients. All hearts were cold preserved with Celsior and underwent ex situ P MRS to measure ratios of various high-energy phosphate metabolites and the intracellular pH (pHi). RESULTS: The total duration of the MRS procedure was 32 min, thereby not unacceptably increasing the total ischemic time for the transplanted grafts. Phosphocreatine (PCr) and inorganic phosphate (Pi ) was significantly different between the two groups (0.95+/-0.29 for TS1 and 2.05+/-0.74 for TS2). The difference in pHi was also significant (7.44+/-0.13 for TS1 and 7.64+/-0.19 for TS2). CONCLUSIONS: Determination of PCr-Pi and pHi as markers of ischemic injury before transplantation can be considered as an objective and accurate criterion for the decision to accept or refuse heart grafts for transplantation.

Adult↗
PubMedDate not supplied

Remodeling of Na,K-ATPase, and membrane fluidity after atrial fibrillation in sheep.

UNLABELLED: Atrial fibrillation (AF) is accompanied by various changes in ion channels that cause atrial electrophysiological remodeling. The enzyme Na,K-ATPase is also a major cellular mechanism for the regulation of ion homeostasis. During AF, Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits as well as changes in membrane fluidity. To test this hypothesis, we studied the effect of pacing-induced AF in sheep on atrial Na,K-ATPase alpha- and beta-subunits and on membrane fluidity as well. METHODS: A group of six sheep (AF group) was subjected to overdrive electrical stimulation of the right atrium in order to induce AF. A group of six sham operated sheep served as control. All paced sheep developed multiple episodes of sustained AF with a mean total duration of 110 min over a 2-hours period. Protein expression of Na,K-ATPase alpha- and beta-subunits in atrial microsomal membranes was assayed by Western blotting analysis. When significant changes in membrane expression were observed, transcriptional regulation was analysed by Northern blotting. Membrane fluidity was assessed on atrial microsomal fractions by anisotropy measurements using the fluorescent probe diphenylhexatriene. RESULTS: Atrial fibrillation enhanced the expression of the Na,K-ATPase beta1-subunit at both membrane and mRNA levels. Anisotropy values were higher in AF group than in control group, indicating a decreased fluidity of the membranes isolated from paced sheep atria. CONCLUSION: These data are the first evidence for an enhanced Na,K-ATPase beta1-subunit expression in membrane during AF. Membrane rigification represents a new factor of tachycardia-induced atrial remodeling.

Animals↗