Effect of prenatal phenytoin administration on the fine structure of rat myocardium and aorta.

Phenytoin (PHT) is an antiepileptic drug known to have teratogenic effects. The aim of this study was to examine the ultrastructure of the left ventricle, the left atrium, and the aorta of 3-month-old offspring and 4-month-old mother animals after oral PHT (150 mg/kg/day) administration to Wistar/DV rats on days 7-18 of gestation. Electron microscopy of the myocardium revealed a heterogeneous population of cardiomyocytes with conventional architecture, and hypoxia/ischemia-like subcellular changes. Cardiomyocytes of offspring hearts were more vulnerable to PHT administration compared with the mother animals. Atrial cardiomyocytes of both mother animals and offspring were less affected by PHT than the ventricular ones. In the myocardium, both interstitial fibrosis and injury of capillaries were noted. Electron microscopy of the aorta revealed a higher resistance of maternal endothelial and smooth muscle cells to PHT compared with offspring cells. Nuclei of endothelial and smooth muscle cells showed pronounced mitotic activity with one and/or two hyperactive nucleoli, more frequently observed in offspring. PHT administration resulted in aortic arteriogenesis in both offspring and mother animals. Interestingly, bundles of myocardial fibers consisting of ischemia-like altered cardiomyocytes with own capillary network were noted in off-spring aortic adventitia. These results are indicative of harmful effects of PHT on rat myocardium and aorta.