Homologies for congenital heart diseases: Murine models, influenced by dextroamphetamine

Abstract

The spontaneous occurrence and teratogenic production of atrial septal defect in A/J mice and ventricular septal defect in C57BL/6J mice lead to the proposal that these strains may represent animal homologies of these congenital heart diseases in human beings. Such models permit investigation into the mechanisms by which nongenetic factors cause genetically predisposed individuals to reach a particular threshold of developmental abnormality and develop a specific type of cardiac malformation.

Amphetamine Addiction and Pregnancy

“…During one of the four pregnancies there was to our knowledge a concomitant alcohol abuse. In experimental animals, amphetamine was shown to act as a mild teratogen when high doses were used (12,20). In retrospective studies of specific anomalies in humans, mothers of infants with biliary atresia and congenital heart defects were found to have a high incidence of amphetamine ingestion during pregnancy (14,21).…”

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of amphetamine and methamphetamine

“…For example, there was no information given on randomization method, maternal and fetal body weight during the study, or litter data (number of litters/group, average litter size, litter weights, etc.). Although there were only two additional dams in the d ‐amphetamine‐treated versus control A/J mice (34 treated females vs. 32 controls) in the 1968 study (Nora et al, 1968), there were 50 more live fetuses and 69 more resorbed fetuses than were seen in the control group, which may be further evidence that the total number of fetuses should have been 183 rather than 283, as printed. There was no mention of the statistical methods employed and litter‐based analyses were not conducted.…”

“…Nora et al ( 1965 , 1968 ) , in two studies funded by NIH, the National Research Council of Canada, or the March of Dimes, examined teratogenicity in A/Jax mice and C57Bl/6J mice dosed with d ‐amphetamine sulfate [purity not specified] . On GD 8 [plug day not specified] the mice received a single i.p.…”

“…In the second study, there were 34 treated and 32 control A/Jax dams and 26 treated and 27 control C57Bl/6J dams (Nora et al, 1968). For the A/Jax mice, there were 283 living treated fetuses and 233 living control fetuses.…”

Thyroxin-Induced Differential Mortality of Mouse Embryos with Cleft Lip

“…In A/HeJ, but not CL/Fr, several embryos, all with normal lips, had marked edema (1 living control and 5 dead treated). Possibly this reflects a liability to heart defects in A/ HeJ {Grabowski, 1978;Nora et al, 1968).…”