Spontaneous and induced alterations in the cardiac membranous ventricular septum of fetal, weanling, and adult rats

Abstract

Alterations of the cardiac membranous ventricular septum were studied using macrodissection, scanning electron and light microscopy of fetal, weanling, and adult Sprague-Dawley rats. Membranous ventricular septal defects (VSDs) were observed in 2.0% of fetuses on day 21 postcoitus (pc) but not in weanling or adult rats. The most common observation was a nonpatent depression in the membranous septum with an incidence of 38.1, 10.5, 4.3% for fetuses on days 17, 19, or 21 pc, respectively, 11.8% for weanlings, and 9.1% for adults. VSDs were characterized by a split in the endocardial cushion cells in the interventricular component of the membranous septum. Nonpatent depressions were characterized by a split in the endocardial cushion cells in the atrioventricular component of the septum, and they persisted postnatally as a blind-ended diverticulum directed above the tricuspid valve. The cardiovascular teratogens, trimethadione and trypan blue, produced in fetuses nonpatent depressions and VSDs morphologically similar to untreated fetuses. Maternal diet restriction (25% of controls) lowered fetal (day 21 pc) body weight by 47% but did not affect the incidence of ventricular septal alterations, suggesting that intrauterine growth retardation is not necessarily associated with alterations in the development of the ventricular septum. We conclude that neither VSDs nor nonpatent depressions in Sprague-Dawley rats affect postnatal survival and that VSDs close spontaneously during neonatal life.

Noninvasive High‐Resolution Ultrasound Reveals Structural and Functional Deficits in Dimethadione‐Exposed Fetal Rat Hearts In Utero

“…Trimethadione is a potent inducer of heart malformations in humans and a number of experimental animal models (Feldman et al, ; Rischbieth, ; Veuthey et al, ; Solomon et al, ; Fleeman et al, ). It is believed that dimethadione, the N‐demethylated metabolite of trimethadione, is the proximate teratogen (Buttar et al, ; Wells, ) and we have previously demonstrated that direct administration of DMO induces a number of cardiac malformations including both membranous and muscular VSDs, outflow tract anomalies, and “sponge‐like” myocardium, which would be anticipated to impair cardiac function both in utero and postnatally (Weston et al, ).…”

Improved technique for fetal heart examination in developmental toxicity studies in rats

“…1H,K), the area of the membranous portion was small and therefore, the detection of VSD was more difficult. However, when the membranous portion was widely expanded, the depression (Solomon et al . 1997) in this portion was shallow; therefore, VSD was detected easily in the Mg/FT fetuses (Fig.…”

Morphological features of mutant rat, IS‐Tlk/Kyo, fetuses with caudal vertebral anomalies

“…However, environmental and genetic factors seem to be involved. VSD is found in rat fetuses or chick embryos treated with trimetadione, typan blue and prenalterol (Bruyere et al 1983;Solomon et al 1997), indicating that one of mechanisms for VSD induction might be related to an increase of cAMP level. On the other hand, genetic breeding studies have demonstrated a close correlation between multiple genetic determinants and induction of VSD in two inbred animal sub-lines (Fox 1967(Fox , 1969Kuribayashi et al 1990Kuribayashi et al , 1991 as well as Long-Evans rats (Fox 1967), brown Leghorn chickens (Siller 1958), and keeshonden (Patterson et al 1974).…”