An electrocardiographic study of cardiovascular problems in mirex-fed rat fetuses

Sperm-positive female rats were intubated with pesticide, Mirex, in oil (5 to 10 mg/kg) on days 8 1/2 to 15 1/2. Controls were untreated or oil-fed. Testing was done on day 18 1/2. Fetuses were sequentially exposed and ECGs obtained with the fetus attached to the placenta and uterus. Counterparts of standard leads, I, II and III were used. Fetuses were weighed and examined afterwards. Swollen fetuses were rated on a scale of 1 (slight edema under chin) to 5 (3 mm edema across back). ECGs from 81 controls and 205 Mirex fetuses were obtained. They were evaluated for rate of heart beat, regularity of beat, PR intervals, and other features. One control exhibited an abnormality, a transitory period of premature atrial contractions. Mirex-fed fetuses frequently exhibited tachycardia, closely correlated with degree of edema. The heart rate increased from 150/minute in controls to 180 in slightly swollen to 224 in swollen fetuses. Mean PR intervals increased with degree of swelling and with dose. The frequency of first degree heart-block was also dose-related, ranging from 20% in the 5 mg/kg group to 77% in the 10 mg/kg group. Second-degree heart-blocks were found in 8%, 3% showed arrhythmias, and one had atrial flutter/fibrillation. These cardiovascular problems seem primarily related to the Mirex-induced edema and demonstrate that fetal edema is not innocuous. These data demonstrate the usefulness of fetal electrocardiography to detect functional teratology.