Inotropic effect of increasing concentration of Ca2+ in the fetal rat heart with retinoic acid-induced malformations.

Cardiac malformations (pulmonary trunk stenosis, ventricular septal defect, and double outlet right ventricle) were induced by the administration of two doses of retinoic acid (RA) to Wistar rats on d 13 of pregnancy. Contractile performance of the isolated perfused rat heart and its inotropic response to Ca2+ (0.6-10.0 mmol.L-1) was studied in 20-d-old fetuses. The body weight of RA-exposed fetuses was significantly lower compared with controls. RA negatively influenced the contractile parameters of the fetal rat heart. The most pronounced effect was, except at a Ca2+ concentration of 2.5 mmol.L-1, observed at developed force at all other concentrations. Simultaneously, the sensitivity to Ca2+, expressed as the Ca2+ concentration at which 30% of maximum was attained, ws significantly lower in RA-exposed hearts. This implies that the malformed heart is more dependent on the extracellular sources of Ca2+.