Left ventricular alterations in a model of fetal left ventricular overload
| Autor: | Guy Michel Mazmanian, Nicolas Bonnet, Alain Serraf, Catherine Rucker-Martin, F. Samson, Dimitri O Levitsky, Michèle Heimburger, Jean-Jacques Mercadier |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Aortic arch
medicine.medical_specialty Hemodynamics Aorta Thoracic Gestational Age Calcium-Transporting ATPases Aortic Coarctation Gene Expression Regulation Enzymologic Muscle hypertrophy Sarcoplasmic Reticulum Calcium-Transporting ATPases Pregnancy Internal medicine Ductus arteriosus medicine.artery medicine Animals Foramen ovale (heart) Pressure overload Fetus Sheep business.industry Myocardium Gene Expression Regulation Developmental Heart Disease Models Animal medicine.anatomical_structure Great arteries Pediatrics Perinatology and Child Health cardiovascular system Cardiology Female Hypertrophy Left Ventricular business |
| Zdroj: | Pediatric research. 48(1) |
| ISSN: | 0031-3998 |
| Popis: | Congenital aortic coarctation is well tolerated by the fetus because the foramen ovale and ductus arteriosus equalize intracardiac and great arteries pressures and shunts. The pathologic consequences only emerge after birth with closure of the foramen ovale and ductus arteriosus. There is, however, no documentation of myocardial effects in utero of the left ventricular (LV) pressure overload induced by aortic banding. We investigated whether prenatal aortic banding could be detrimental at the structural and/or functional level. The goal of the present study was to investigate the cardiac effects of LV pressure overload in a fetal lamb model. Nine fetal lambs underwent preductal banding of the aortic arch in utero at midgestation (CoA group), whereas their twins underwent sham surgery. All fetuses were studied between 27 and 37 d after surgery for LV pressure, anatomic and histologic anomalies, and steady state sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA and protein levels and pump activity. Surgery resulted in severe aortic coarctation in all the animals in the CoA group and was associated with a 65% increase in the LV weight to body weight ratio relative to the sham-operated group (p < 0.001). Hemodynamic and histologic studies showed an evolutionary pattern depending on duration of the experimental coarctation with a shift occurring at 30 d of coarctation. The initial response of cardiomyocytes to ventricular overload was hypertrophy of the myocytes, followed by myocyte hyperplasia. Compared with sham, there was an apparent decrease in the percentage of binucleated cells in the CoA group after 30 d of coarctation. The earliest response to LV pressure overload appears to occur at the molecular level. Indeed, sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA levels fell significantly to only 28.6% of the sham group value (p = 0.023), independently of the duration of coarctation. In the fetal lamb, the pressure overload-induced hypertrophy resulting from progressive aortic coarctation leads to hemodynamic and lesional abnormalities and slows ontogenic maturation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|