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Biomedical subjects

Nathalie Roy

Publications and source records attributed to Nathalie Roy.

10 recordsLinked to original sources

Vascular endothelial growth factor prevents apoptosis and preserves contractile function in hypertrophied infant heart.

BACKGROUND: Cardiac hypertrophy is an adaptive response to increased workload that, if unrelieved, leads to heart failure. It has been reported that cardiomyocyte apoptosis contributes to failure, and that vascular endothelial growth factor (VEGF) treatment of hypertrophied myocardium increases capillary density and improves myocardial perfusion. In this study we hypothesized that VEGF treatment reduces cardiomyocyte apoptosis and thereby preserves myocardial contractile function. METHODS AND RESULTS: Newborn rabbits underwent aortic banding. At 4 and 6 weeks of age, hypertrophied animals were treated with intrapericardial administration of recombinant VEGF protein. Three groups of animals were investigated: age-matched controls (C), untreated hypertrophied (H), and VEGF-treated hypertrophied hearts (T). Cardiomyocyte apoptosis was determined by TUNEL staining and PARP cleavage (immunoblotting of nuclear extracts) and cardiac function by transthoracic echocardiography. Death attributable to severe heart failure occurred in 14 of 43 untreated and 2 of 29 VEGF-treated animals (P<0.01). TUNEL-positive cardiomyocyte nuclei (n/1000 nuclei) were significantly increased in untreated hearts at 5 weeks (H: 10+/-1.8 versus T: 3+/-0.7) and at 7 weeks (H: 13+/-3.6 versus T: 5+/-1.5; P<0.05). Increased apoptosis in untreated hypertrophy was also confirmed by the presence of PARP cleavage (H: 74+/-7 versus T: 41+/-4 arbitrary densitometry units; P<0.05). VEGF treatment preserved left ventricular mass, prevented dilation (T: 1.01+/-0.06 versus H: 0.77+/-0.07; P<0.05), and preserved contractility indices compared with untreated hearts. CONCLUSIONS: Lack of adaptive capillary growth impairs myocardial perfusion and substrate delivery in hypertrophying myocardium. VEGF treatment reduces myocardial apoptosis and prolongs survival in a model of severe progressive left ventricular hypertrophy. Promoting capillary growth with VEGF reduces apoptosis, preserves myocardial contractile function, and delays the onset of failure in pressure-loaded infant myocardium.

Animals↗

Dopamine induces postischemic cardiomyocyte apoptosis in vivo: an effect ameliorated by propofol.

BACKGROUND: Dopamine is commonly used to improve postischemic myocardial contractile function. However, there is evidence that dopamine augments apoptosis after ischemia through increased intracellular calcium and opening of the mitochondrial permeability transition pore. Propofol (2,6-diisopropylphenol) is an anesthetic that has been shown to prevent mitochondrial permeability transition pore opening. We evaluated the effects of propofol given during reperfusion on dopamine-mediated apoptosis. METHODS: Hearts from 8-week-old inbred New Zealand White rabbit siblings were subjected to 2 hours of cold cardioplegic ischemia and 6 hours of reperfusion in a heterotopic transplant model. Controls consisted of the recipient rabbit's nonischemic heart. The ischemia-reperfusion (IR) group consisted of postischemic hearts reperfused with no drugs; the IR plus dopamine (IR+D) group received dopamine (20 microg x kg(-1) x min(-1)) continuously; the IR+D plus propofol (IR+D+P) group received dopamine (20 microg x kg(-1) x min(-1)) plus propofol (500 to 600 microg x kg(-1) x min(-1)); and the IR plus propofol (IR+P) group received propofol only (500 to 600 microg x kg(-1) x min(-1)) throughout reperfusion (n = 7 to 9 in each group). Myocardial function was measured using a left ventricular balloon; terminal nick-end labeling (TUNEL) staining, DNA electrophoresis, and immunoblotting for caspase-3 cleavage were performed at the end of reperfusion. RESULTS: Dopamine increased the number of TUNEL-positive nuclei significantly (14.0 +/- 2.0/1,000 for IR+D versus 6.7 +/- 2.0/1,000 for IR, p = 0.01). Propofol (IR+D+P) reduced the total number of apoptotic cells in hearts receiving dopamine (7.1 +/- 1.8/1,000, p = 0.01 versus IR+D) to the extent seen in IR alone. DNA laddering and caspase-3 cleavage were observed at greater frequency in the IR+D group compared with the IR and IR+D+P groups. Propofol had no effect on dopamine-mediated increased systolic function, but improved diastolic function after ischemia. CONCLUSIONS: Dopamine infusion has a positive inotropic effect on the postischemic heart at the expense of increased cardiomyocyte apoptosis. The addition of propofol prevents dopamine-induced apoptosis after ischemia while maintaining positive inotropy.

Anesthetics, Intravenous↗

Cardiac conduction through engineered tissue.

In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal's natural life. Perfusion of hearts with fluorescently labeled lec-tin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding re-cipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy.

Animals↗

Multiple-scattering-based lidar retrieval: method and results of cloud probings.

Recent developments in the search for a practical method of exploiting the multiple-scattering contributions to lidar returns are consolidated in a robust retrieval algorithm. The theoretical basis is the small-angle diffusion approximation. This implies that the algorithm is limited to media of sufficient optical thickness to generate measurable multiple scattering and to geometries for which the receiver's footprint diameter is less than the scattering mean free path. The primary retrieval products are the range-resolved extinction coefficient and the effective particle diameter from which secondary products such as the particle volume mixing ratio and the extinction at other wavelengths can be calculated. We recall briefly earlier validation tests and present new data and analysis that demonstrate and quantify the solutions' accuracy. The results show that systematic lidar probings with the proposed multiple-scattering technique can provide valuable physical information on cloud formation and evolution.

Journal Article↗

Mycotic aneurysm of the descending thoracic aorta in a 2-kg neonate.

Umbilical artery catheterization is often performed in critically ill neonates. Infection and thromboembolic events are relatively frequent complications, but aneurysm formation is rare. We describe the case of a premature baby who developed a rapidly expanding aneurysm of the descending thoracic aorta, secondary to a highly placed infected umbilical catheter. The rapid progression under medical therapy prompted us to replace the thoracic aorta with an 8-mm polytetrafluoroethylene graft, using extracorporeal circulation and core cooling. The baby had an excellent recovery and was discharged home after a prolonged antibiotic course. He is being followed with repeated imaging studies for a small abdominal aneurysm. We describe a novel approach to this rare and complicated problem and provide a review of the literature on the subject.

Anti-Bacterial Agents↗

Measurement of the azimuthal dependence of cross-polarized lidar returns and its relation to optical depth.

We measure with a gated intensified CCD camera the cross-polarized backscattered light from a linearly polarized laser beam penetrating a cloud made of spherical particles. In accordance with previously published results we observe a clear azimuthal pattern in the recorded images. We show that the pattern is symmetrical, that it originates from second-order scattering, and that higher-order scattering causes blurring that increases with optical depth. We also find that the contrast in the symmetrical features can be related to measurement of the optical depth. Moreover, when the blurring contributions are identified and subtracted, the resulting pattern provides a pure second-order scattering measurement that can be used for retrieval of droplet size.

Journal Article↗

Immature intrapericardial teratoma in a newborn with elevated alpha-fetoprotein.

A large intrapericardial mass was incidentally found in a fetus at 32 weeks gestational age, which was accompanied by a significant pericardial effusion. The baby was delivered by cesarean section and had surgical removal of the tumor on the second day of life. Alpha-fetoprotein was elevated. The pathologic analysis demonstrated a grade I immature teratoma with foci of hepatoid tissue. The patient had an uneventful postoperative recovery. A review of the literature and pathologic implications are discussed.

Adult↗

Retroaortic innominate vein with coarctation of the aorta: surgical repair and embryology review.

A newborn girl with a retroaortic innominate vein, coarctation of the aorta, ventricular septal defect, and subaortic stenosis underwent a complete repair at 8 days of age. The ascending aorta was transected and the innominate vein was brought in front of it. We review the anatomy and embryology of this rare entity and describe the surgical technique to avoid recoarctation and innomante vein compression.

Anastomosis, Surgical↗