Alloxan-induced diabetes mellitus in pregnant sheep and chronic fetal catheterization

Abstract

25 female sheep of the Texel breed were made hyperglycaemic by administration of alloxan monohydrate (ALX) in early pregnancy and 15 ewes served as controls. Average venous glucose levels (mean ± standard deviation) increased from 3·5 ± 0·2 to 14·0 ± 1·8 mmol/l. All hyperglycaemic sheep were treated with long-acting insulin in doses adjusted individually (0·2-1·0 U/kg per day) to keep glucose levels above 8 mmol/l. After a temporary significant increase, maternal venous concentrations of urea and creatinine returned to normal levels. One sheep died on day 6 after administration of ALX. Another hyperglycaemic sheep died at induction of anaesthesia. Eight hyperglycaemic ewes aborted between days 90 and 128 of gestation. Between days 103 and 135 of gestation the remaining hyperglycaemic ( n = 15) and control ( n = 15) ewes were operated upon and the fetuses were provided with EEG, nuchal EMG and ECG electrodes and catheters in the trachea, amniotic fluid, jugular vein and carotid artery. Use of the chronic sheep preparation for the study of diabetes mellitus and fetal reactions was successful in 10 out of 25 cases, as in the diabetic group postoperative intra-uterine fetal survival varied between 2 and 19 days and in 10 cases was at least 5 days. Postoperative intra-uterine fetal survival in the controls was significantly longer and varied between 4 and 28 days, and in 13 cases was at least 5 days. A highly significant correlation ( P < 10-6) between maternal and fetal blood glucose levels was seen. After 5 days of postoperative recovery fetal blood glucose levels were 3·8 ± 1·3 mmol/l in the hyperglycaemic group compared with 0·5 ± 0·2 mmol/l in the control group. The fetal clinical condition as measured by fetal arterial blood gases did not differ significantly between the hyperglycaemic and control groups. Fetal plasma insulin levels in the hyperglycaemic group did not differ significantly from the control group levels. The birth-weights of the fetuses of the ALX-treated sheep were significantly lower compared with control fetuses.