To investigate the relationship between imbalance of cardiac autonomic nervous system and sudden death in fetuses of rats with intrahepatic cholestasis of pregnancy (ICP), the animal model of ICP was induced by hypodermic injection of 17-alpha-ethinylestradiol and progesterone. The electrocardiograms and frequency domain analysis of heart rate variability (HRV) including low frequency (LF), high frequency (HF) and the ratio between low and high frequencies (LF/HF) of fetal rats by the 21st day of gestation were evaluated with Chart 5 software of Powerlab biologic signal extracting and analyzing system.
Results: (1) The serum total bile acids (TBA) levels of pregnant rats were (78.5 +/- 4.5) micromol/L in Group ICP and (24.6 +/- 3.6) micromol/L in Group control; significant difference was noted between the two groups (P < 0.01). (2) In Group ICP, fetal rats arrhythmias appeared after (29.3 +/- 6.4) minutes' observation, and fetal rats died suddenly after (23.5 +/- 4.6) minutes' arrhythmias; However, the fetal rats in Group control all showed normal electrocardiograms over 90 minutes' continuous observation. (3) The values of LF and LF/HF of fetal rats in Group ICP within 20 minutes before fetal rats arrhythmias were significantly higher than those in Group control (LF 48.45 +/- 4.11 nu vs. 33.87 +/- 4.31 nu, and LF/HF 0.99 +/- 0.14 vs. 0.61 +/- 0.10, respectively, P < 0.01). (4) Dynamic power spectral analysis of HRV indicated that the values of LF and LF/HF of fetal rats in Group ICP increased progressively within 15 minutes before the sudden death of fetal rats. These demonstrated that autonomic imbalance in association with increased sympathetic activity has been strongly implicated in the pathophysiology of fetal arrhythmogenesis and sudden death in ICP. HRV analysis could be a useful tool for fetal surveillance, especially for ICP.