Stereological study of stage 34 chicken hearts with looping disturbances after retinoic acid treatment: Disturbed growth of myocardium and atrioventricular cushion tissue

Abstract

Background: In a previous study retinoic acid treatment of chicken hearts has resulted in a spectrum of looping disturbances. Because of a decrease in contraction force of these hearts, the myocardial volume was hypothesized to be altered. Because retinoic acid has been suggested to influence endocardial cushion volumes, these were estimated as well.Methods: The previously studied hearts were used for estimating the absolute volumes of the atrial and ventricular myocardium and of the endocardial cushions by means of Cavalieri's principle. To measure the surface density of the trabeculations according to the isector method, we used retinoic acid treated hearts, which were perfusion fixed and in which the sections were isotropic uniform random. The volumes and surface densities found in the three morphologically distinguished groups, i.e., intact septum, isolated ventricular septal defect and double outlet right ventricle, were compared with those in shams.Results: A significant volume decrease was found in the right ventricular free wall myocardium of the double outlet right ventricle. No significant differences were found in the surface densities of the trabeculae. The volume of the atrioventricular cushion tissue in the double outlet right ventricle hearts was significantly increased. The morphological spectrum observed previously was also expressed in the right ventricular myocardial volume, which appeared to decrease from the least to the most malformed hearts, and in the volume of the atrioventricular cushion tissue, which appeared to increase.Conclusions: Several studies have shown pathology in myocardial and cushion tissue after retinoic acid treatment. In this study we have found a decreased growth of the right ventricular myocardium and an increased growth of the atrioventricular cushion tissue. We suggest that the previously found looping disturbance causes changed hemodynamics, as reported elsewhere, and that these result in changes in growth. We cannot exclude a direct effect of retinoic acid on the myocardium, which has to explain the looping disturbance. Anat.

Cardiovascular Defects Associated With Abnormalities in Midline Development in the Loop-tail Mouse Mutant

“…In the chick embryo, treatment with retinoic acid at stage 15 of development appears to induce cardiac looping abnormalities, leading to a spectrum of double-outlet right ventricle and ventricular septal defects. 20,24 The cardiac alignment defects described in these embryos closely resemble the abnormalities that we observe in Lp/Lp fetuses.…”

Retinoic acid administration is associated with changes in the extracellular matrix and cardiac mesenchyme within the endocardial cushion

“…Moreover this change resulted in a decrease in mesenchyme formation in a culture bioassay of mesenchyme formation (Yan et al, 2000). These studies were in agreement with other studies in which RA was added to chick and mouse embryos (Davis and Sadler, 1981;Bouman et al, 1995;Nakajima et al, 1996Nakajima et al, , 1997Bouman et al, 1997Bouman et al, , 1998.…”

Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions

“…Quite straightforward solution is the measurement of compact myocardium thickness, which is altered under changed pressure loading (Sedmera et al, 1998), and in some mutant mice with cardiac phenotype (“thin myocardium syndrome”) where it is usually associated with poor survival in later fetal development (e.g., Sucov et al, 1994; Kastner et al, 1994; Jaber et al, 1996). Estimation of myocardial volumes in different compartments is informative and reliable, but requires time‐consuming point counting (Bouman et al, 1997). The value of simple length and area measurements giving a general idea about heart shape and dimensions should not be underestimated.…”