Antiheart antibody production of cardiovascular malformations in the mouse: A preliminary study

Abstract

Cardiovascular malformations were produced in 17% of A/J and C57BL/6 mice using isogeneic antiheart antibody (RAMHS) and in 22% of C57BL/6 mice using allogeneic RAMHS by injecting on four consecutive days of gestation (days 8–11 or 12–15). The antiheart antibody was raised in rabbits and adsorbed against mouse kidney and liver to yield an antiserum with high antiheart activity and low activity against other organs, demonstrably kidney. Cardiovascular maldevelopment occurred in 9% of mice injected with antikidney antibody (RAMKS), 7% receiving normal rabbit serum, and 1% receiving normal saline. A highly significant (P < .001) difference between all of the RAMHS and the normal saline groups demonstrated that antiheart antibody is teratogenic to the developing heart; and a significant difference (P < .05) between allogenic RAMHS and RAMKS antibody in the frequency of induction of cardiovascular anomalies suggests that there is organ‐specific activity to antiheart antibody. The type of cardiovascular anomalies caused in the mice studied were the same (VSD in C57BL and ASD in A/J) as those that occur spontaneously or are produced by other teratogens such as dextroamphetamine. Antiheart antibody thus did not appear to produce a specific type of maldevelopment but rather made manifest the malformation to which there appears to be a hereditary predisposition (genetic‐environmental interaction).

The Production of Cardiovascular Malformations with Combined Use of Antisera to Kidney and Fetal Heart

“…Ventricular septa1 defects, aortic arch anomalies, and double outlet right ventricle were the most common cardiovascular malformations observed. These results were similar to our previous finding using adult rat heart antiserum, and suggest that AFHS alone is not teratogenic, but when combined with a sub-teratogenic dose of AKS it becomes teratogenic and organ specific.There have been several reports on induction of cardiovascular malformations by administering anti-heart sera to pregnant rats or mice, but the malformation rate has been generally low (Barrow and Taylor, 1971;Nora et al, 1974;Miyata et al, 1984).However, when direct impairment of fetal organs is considered, administration of antiserum to fetal tissue itself may produce severe anomalies. In the present experiments, pregnant rats were administered anti-fetal-heart serum alone or in combination with a sub-teratogenic dose of antikidney serum in order to compare the results of the administration of rabbit anti-adult-rat-heart serum (AAHS).…”

“…There have been several reports on induction of cardiovascular malformations by administering anti-heart sera to pregnant rats or mice, but the malformation rate has been generally low (Barrow and Taylor, 1971;Nora et al, 1974;Miyata et al, 1984).…”