Role of sympathetic activity in the generation of heart rate and arterial pressure variability in fetal sheep

Significant fluctuation in heart rate (HR) and arterial pressure occur during fetal life. However, the mechanisms regulating this normal variability are not completely understood. To test the hypothesis that the normal variability in fetal HR and blood pressure are produced by intrinsic fluctuations in sympathetic outflow, we recorded HR, mean arterial blood pressure (MABP), and renal sympathetic nerve activity (RSNA) in conscious, chronically instrumented, near-term fetal sheep (n = 5; 132-137 d of gestation, term being 145 d) and correlated the relationships between RSNA and MABP, and RSNA and HR. RSNA, HR, and MABP were sampled at a frequency of 4 Hz and the values averaged by 5-min blocks over a 4-h period. Linear regression analysis demonstrated a positive correlation between RSNA and both HR and MABP in all five fetuses (p < 0.02). In a second group of fetuses (n = 5), ganglionic blockade with trimethaphan (150-250 mg/kg/min) significantly attenuated (p < 0.05) the coefficients of variation of HR (12.3 +/- 1.9% versus 1.7 +/- 0.6%) and MABP (5.8 +/- 0.6% versus 3.6 +/- 0.5%). These results demonstrate that, in the fetus, fluctuations in HR and MABP are mediated by changes in sympathetic outflow and suggest an important role for the autonomic nervous system in fetal cardiovascular regulation.