Biomedical subjects

Françoise Lallemand

Publications and source records attributed to Françoise Lallemand.

6 recordsLinked to original sources

PubMed2007

NADPH oxidase inhibition prevents cocaine-induced up-regulation of xanthine oxidoreductase and cardiac dysfunction.

Oxidative stress is involved in the pathogenesis of cocaine-induced cardiomyopathy. In the present study, we aimed to determine the enzymatic sources of reactive oxygen species (ROS) production, namely NADPH oxidase and xanthine oxidoreductase (XOR) in male Wistar rats treated for 7 days with cocaine (2x7.5 mg/kg/day, ip) or cocaine with a NADPH oxidase inhibitor (apocynin, 50 mg/kg/day, po) or a XOR inhibitor (allopurinol, 50 mg/kg/day, po). Cocaine-induced cardiac dysfunction is associated with an increase in NADPH oxidase and XOR activities (59% and 29%, respectively) and a decrease in catalase activity. Apocynin or allopurinol treatment prevents the cocaine-induced cardiac alteration by restoration of cardiac output, stroke volume and fractional shortening. This is associated with a reduction of the myocardial production of superoxide anions and an enhancement of catalase activity. Surprisingly, apocynin treatment prevents XOR up-regulation supporting the hypothesis that NADPH oxidase-derived ROS play a role in modulating ROS production by XOR. These data suggest that NADPH and xanthine oxidase act synergically to form myocardial ROS and clearly demonstrate that their inhibition may be critical in preventing the initiation and progression of cocaine-induced LV dysfunction.

Acetophenones↗

PubMed2006

Low molecular weight fucan prevents transplant coronaropathy in rat cardiac allograft model.

INTRODUCTION: Transplant arteriosclerosis is the main cause of long-term failure after cardiac transplantation. Vascular rejection is thought to be due to intimal proliferation occurring in response to arterial wall immune-mediated injury. A low molecular weight fucan (LMWF) compound, a sulfated polysaccharide, has been demonstrated to increase plasma levels of stromal cell-derived factor 1 (SDF-1) and consequently to mobilize bone marrow-derived vascular progenitor cells (BMVPC). The aim of this study was to evaluate the capacity of LMWF to prevent coronary intimal proliferation in a rat cardiac allograft model. METHODS: Heterotopic abdominal cardiac graftings were performed in Brown Norway (BN) and Lewis (LEW) rats. Animals were divided into 4 groups of 10 rats. Two groups were treated intramuscularly with LMWF (5 mg/kg/day) (one BN to BN isograft group, and one BN to LEW allograft group); and two control groups were LMWF-untreated (one BN to BN isograft group and one BN to LEW allograft group). All animals were treated by cyclosporin (15 mg/kg/day) sub-cutaneously and sacrificed at day 30. The cardiac grafts were assessed by morphometry of structural parameters and by histological and immunohistochemical analyses. RESULTS: All cardiac isografts were devoid of any coronary and parenchymal lesions. In contrast, the majority of untreated allografts developed coronary intimal proliferation in close association with intimal and adventitial inflammatory CD68(+) cell infiltration. Further, the parenchyma exhibited large areas of actin(+) cells (myofibroblasts) of recipient origin colocalized with the CD68(+) infiltrating cells. Interestingly, all LMWF-treated allografts were well protected against coronary and parenchymal lesions and the coronary arteries exhibited an intimal monolayer of flat cells, which however were CD34 negative. CONCLUSION: treatment with LMWF appeared very effective in this rat cardiac allograft model to prevent arterial and parenchymal lesions occurring in response to alloimmune injury. However this protective effect does not appear to depend on mobilization of bone marrow-derived cells.

Animals↗

PubMed2006

Insights into gene expression changes impacting B-cell transformation: cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells.

Large-animal models for leukemia have the potential to aid in the understanding of networks that contribute to oncogenesis. Infection of cattle and sheep with bovine leukemia virus (BLV), a complex retrovirus related to human T-cell leukemia virus type 1 (HTLV-1), is associated with the development of B-cell leukemia. Whereas the natural disease in cattle is characterized by a low tumor incidence, experimental infection of sheep leads to overt leukemia in the majority of infected animals, providing a model for studying the pathogenesis associated with BLV and HTLV-1. Tax(BLV), the major oncoprotein, initiates a cascade of events leading toward malignancy, although the basis of transformation is not fully understood. We have taken a cross-species ovine-to-human microarray approach to identify Tax(BLV)-responsive transcriptional changes in two sets of cultured ovine B cells following retroviral vector-mediated delivery of Tax(BLV). Using cDNA-spotted microarrays comprising 10,336 human genes/expressed sequence tags, we identified a cohort of differentially expressed genes, including genes related to apoptosis, DNA transcription, and repair; proto-oncogenes; cell cycle regulators; transcription factors; small Rho GTPases/GTPase-binding proteins; and previously reported Tax(HTLV-1)-responsive genes. Interestingly, genes known to be associated with human neoplasia, especially B-cell malignancies, were extensively represented. Others were novel or unexpected. The results suggest that Tax(BLV) deregulates a broad network of interrelated pathways rather than a single B-lineage-specific regulatory process. Although cross-species approaches do not permit a comprehensive analysis of gene expression patterns, they can provide initial clues for the functional roles of genes that participate in B-cell transformation and pinpoint molecular targets not identified using other methods in animal models.

Animals↗

PubMed2004

Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure.

BACKGROUND: Heart rate reduction (HRR) improves left ventricular (LV) filling, increases myocardial O2 supply, and reduces myocardial O2 consumption, which are all beneficial in congestive heart failure (CHF). However, the long-term effects of HRR on cardiac function and remodeling are unknown. METHODS AND RESULTS: We assessed, in rats with CHF, the effects of long-term HRR induced by the selective I(f) current inhibitor ivabradine (as food admix for 90 days starting 7 days after coronary artery ligation). To assess intrinsic modifications of LV tissue induced by long-term HRR, all parameters were reassessed 3 days after interruption of treatment. Ivabradine decreased heart rate over the 90-day treatment period (-18% versus untreated at 10 mg x kg(-1) x d(-1)), without modifying blood pressure, LV end-diastolic pressure, or dP/dt(max/min). Ivabradine significantly reduced LV end-systolic but not end-diastolic diameter, which resulted in preserved cardiac output due to increased stroke volume. In the Langendorff preparation, ivabradine shifted LV systolic but not end-diastolic pressure-volume relations to the left. Ivabradine decreased LV collagen density and increased LV capillary density without modifying LV weight. Three days after interruption of treatment, the effects of ivabradine on LV geometry, shortening, and stroke volume persisted despite normalization of heart rate. CONCLUSIONS: In rats with CHF, long-term HRR induced by the selective I(f) inhibitor ivabradine improves LV function and increases stroke volume, preserving cardiac output despite the HRR. The improvement of cardiac function is related not only to the HRR per se but also to modifications in the extracellular matrix and/or function of myocytes as a consequence of long-term HRR.

Animals↗

PubMed2004

Tissue Doppler imaging detects early asymptomatic myocardial abnormalities in a dog model of Duchenne's cardiomyopathy.

AIMS: Early diagnosis of Duchenne's dilated cardiomyopathy remains a challenge for conventional echocardiography. We sought to determine whether tissue Doppler imaging (TDI) could detect early alteration in myocardial function in a dog model of Duchenne muscular dystrophy, i.e. the Golden Retriever Muscular Dystrophy (GRMD). METHODS AND RESULTS: Myocardial function was assessed by TDI in 20 dogs with normal conventional parameters of systolic function (eight controls and 12 GRMD, 25+/-11 weeks) without knowledge of the genotype. M-mode TDI was recorded from a short-axis view for measurement of endocardial and epicardial velocities and myocardial velocity gradient (MVG) within the posterior wall. Controls and GRMD dogs were comparable regarding left ventricular fractional shortening (37+/-2 vs 42+/-3%, p=ns). Conversely, TDI showed, in all GRMD dogs, a dramatic decrease in systolic MVG (0.8+/-0.1 vs 2.9+/-0.3 s(-1), p<0.0001) and early diastolic MVG (2.3+/-2.2 vs 10.8+/-1.1 s(-1), p<0.0001). This MVG alteration was related to a significant decrease in endocardial velocities in GRMD whereas epicardial velocities were comparable in the two groups. CONCLUSION: These results show that TDI is more sensitive than conventional echocardiography in detecting pre-clinical myocardial abnormalities before occurrence of left ventricular dilation and dysfunction. TDI should be part of the screening techniques for the early diagnosis of cardiomyopathy.

Animals↗

PubMed2003

Prolonged cardiac dysfunction after withdrawal of chronic cocaine exposure in rats.

Cocaine abuse causes myocardial dysfunction and induces oxidative stress. However, the reversibility of these effects is unknown. We evaluated myocardial function and oxidative stress after cocaine withdrawal, in a rat model of chronic cocaine exposure. Standard echocardiography and Doppler tissue imaging were performed after 4 weeks (W4) of cocaine administration (2 x 7.5 mg/kg/d, i.p.) and 4 weeks after interruption (W8). At these time points, redox state (reduced glutathione GSH, oxidized glutathione GSH, and GSH/GSSG) as well as activities of GSH peroxidase (GPX), superoxide dismutase (SOD), and catalase were determined in the left ventricle (LV). At W4, LV fractional shortening, posterior wall thickening, systolic myocardial ventricular gradient (SMVG), dP/dt(max), and dp/dt(min) were decreased, compared with control values while LV myocardial thickness was increased. At W8, even though dP/dtmax and dp/dt(min) were restored, myocardial function was still impaired as demonstrated by the decrease in posterior wall thickening, and systolic myocardial velocity gradient. At W4, CAT and GPX activities as well as GSH/GSSG ratio were reduced while SOD activity was increased. Antioxidant markers and redox ratio remained altered 4 weeks after the last injection. Thus, these data demonstrate the persistence of LV dysfunction after cocaine withdrawal, which occurs in a context of a deficit in antioxidant defenses.

Animals↗