Effect of arginine vasopressin on breathing movements of chronically instrumented fetal lambs.

BACKGROUND: In hypoxic conditions, fetal breathing movements (FBM) are reportedly inhibited with simultaneous elevation of the plasma level of catecholamines and arginine vasopressin (AVP). Although some kinds of catecholamines are reported to inhibit FBM, the effects of AVP on FBM are still unknown. The present study was undertaken to elucidate whether or not AVP has an inhibitory effect on FBM and electrocortical activities in chronically instrumented fetal lambs. METHODS: Arginine vasopressin was injected slowly into the fetal external jugular vein via a catheter over a 30 minute period at an infusion rate of 4.9 approximately 10.0 mIU/minute/body. In 15 fetuses (36 estimations) the mean fetal age, mean estimated fetal body weight, and mean infusion dose were 132.4 +/- 4.5 days, 3.4 +/- 0.3 kg and 1.7 +/- 0.3 mIU/kg/min. RESULTS: The infusion caused a persistent decrease in the fetal heart rate and an increase in the fetal arterial pressure during the 30 minute period. The infusion of AVP resulted in a significant decrease in the incidence of FBM from 36.1 +/- 14.8% to 12.4 +/- 14.9% (p <0.01). However, there were no significant differences in the incidence of the low voltage fast (LVF) activity before and during infusion of AVP. CONCLUSION: AVP has an inhibitory effect on FBM. The mechanism of this inhibition was not a direct suppression of the CNS as there was a dissociation between FBM and the electrocortical activity during infusion of AVP.

Experimentally induced intermittent sinusoidal heart rate pattern and sleep cycle in fetal lambs.

OBJECTIVE: Intermittent sinusoidal heart rate pattern, an early indicator of fetal anemia, has been speculated to have a positive correlation with fetal sleep cycles. To test this hypothesis, intermittent sinusoidal heart rate patterns were produced experimentally with arginine vasopressin in six methylatropinized fetal lambs that were demonstrating clear rapid-eye-movement and non-rapid-eye-movement sleep cycling. STUDY DESIGN: Eleven trials of arginine vasopressin infusion (40 to 160 mIU per body per minute) were performed on each of six chronically instrumented fetal lambs subsequent to parasympathetic blocking doses of methylatropine (300 to 400 micrograms). An intermittent sinusoidal heart rate pattern was observed in relation to fetal sleep cycles. RESULTS: Alteration between rapid-eye-movement and non-rapid-eye-movement sleep was observed in methylatropinized fetuses. In the six fetuses that showed intermittent sinusoidal heart rate patterns subsequent to arginine vasopressin infusion, the fetal heart rate tracing and fetal electrocorticogram demonstrated alternate sinusoidal pattern and reactive heart rate patterns during high- and low-voltage electrocorticogram activity, respectively. CONCLUSION: These findings support the hypothesis that fetal sleep cycling has a positive correlation with the periodic appearance of intermittent sinusoidal heart rate patterns.

Intermittent sinusoidal heart rate pattern in vagotomized fetal lambs.

OBJECTIVES: Our aims were to investigate the relationship between the dose of arginine vasopressin and the pattern and duration of arginine vasopressin-induced sinusoidal fetal heart rate and to elucidate the correlation between intermittent sinusoidal heart rate and fetal sleep cycle. STUDY DESIGN: Sinusoidal heart rate pattern was induced by intravenous arginine vasopressin infusion at doses from 2 to 78 mlU/min into 11 chronically instrumented fetal lambs with bilateral cervical vagotomy. Appearance and frequency of sinusoidal heart rate, intermittent sinusoidal heart rate, and persistent sinusoidal heart rate were observed along with fetal tracheal pressure and electrooculogram. RESULTS: Intermittent sinusoidal heart rate response to low, medium, and high doses of arginine vasopressin appeared in 73.3%, 50.0%, and 33.3% of experiments, respectively. Intermittent sinusoidal heart rate appeared more frequently than persistent sinusoidal heart rate with lower doses (p < 0.02). When intermittent sinusoidal heart rate was induced, the incidence of sinusoidal patterns significantly increased during non-rapid-eye-movement sleep in comparison with rapid-eye-movement sleep (p < 0.01). CONCLUSIONS: Appearance of sinusoidal heart rate seems to be related to the dose of arginine vasopressin infused. Appearance of sinusoidal heart rate is also influenced by fetal sleep cycle; sinusoidal heart rate is more likely to appear during non-rapid-eye-movement sleep than during rapid-eye-movement sleep. These results support the hypothesis that persistent sinusoidal heart rate correlates with severity of stress.

Physiologic baroreceptor activity in the fetal lamb.

OBJECTIVE: We investigated the influences of gestational age and behavioral state on fetal baroreceptor activity. STUDY DESIGN: Two protocols were used to analyze low-voltage fast activity and high-voltage slow activity in eight chronically instrumented ovine fetuses at days 127 to 142. In protocol 1 correction of fetal heart rate to mean arterial blood pressure was assessed under physiologic conditions, and the linear regression slope of fetal heart rate on mean arterial pressure was calculated. In protocol 2 an injection of 7.5 micrograms of norepinephrine was given during consecutive behavioral cycles. The ratio of fetal heart rate decrease to mean arterial pressure increase was determined as representing baroreceptor activity. RESULTS: Under protocol 1 the slope was steeper in high-voltage slow activity (2.33 +/- 1.03) than in low-voltage fast activity (0.89 +/- 0.37) (n = 21, p less than 0.001), indicating that fetal heart rate changes are sensitive to blood pressure changes during high-voltage slow activity. Under protocol 2 inverse relationships were found between the ratio of fetal heart rate decrease to mean arterial pressure increase and gestational age in low-voltage fast activity and high-voltage slow activity. CONCLUSION: Fetal baroreceptor activity increased during high-voltage slow activity and decreased with gestational age.

Autonomic nervous system regulation of baseline heart rate in the fetal lamb.

OBJECTIVE: We examined 29 chronically instrumented fetal lambs from 125 to 143 days' gestation to investigate the effects of fetal behavioral states and autonomic nervous system maturation on baseline fetal heart rate. STUDY DESIGN: Behavioral states were defined from electrocorticographic analysis as low-voltage fast activity or high-voltage slow activity. Decrease and increase in baseline fetal heart rate subsequent to administration of propranolol and methylatropine represented beta-sympathetic and parasympathetic activity. RESULTS: Baseline fetal heart rate decreased with gestation in both states, with steeper regression in low-voltage fast activity (p less than 0.001). Positive correlation was noted between gestational age and percent decrease baseline fetal heart rate in both states with steeper regression in high-voltage slow activity (p less than 0.001), and between gestational age and percent increase baseline fetal heart rate with steeper regression in low-voltage fast activity (p less than 0.001). Fetal heart rate beta-sympathetic and parasympathetic tones increased with age in both states, with elevation of beta-sympathetic tone in high-voltage slow activity and parasympathetic tone in low-voltage fast activity. CONCLUSION: Sympathetic and parasympathetic systems influence baseline fetal heart rate in these behavioral states and with age.

Effect of arginine vasopressin on arterial oxygen partial pressure in the chronically catheterized fetal lamb.

Fetal plasma 2,3-Diphosphoglycerate (2,3-DPG) and glucose levels were observed during infusion of arginine vasopressin into 6 chronically catheterized fetal lambs. Low dose infusion of arginine vasopressin (5-10 mIU/min.) did not change fetal arterial blood gases significantly. At a high concentration of vasopressin (20-40 mIU/min.), infusion for 60 minutes increased fetal arterial pO2 by approximately 5 mmHg (p less than 0.005 by paired t-test), and decreased pCO2 by approximately 2 mmHg (p less than 0.005 by paired t-test) without significant changes in pH. Neither low nor high dose infusion of arginine vasopressin was accompanied by significant changes in 2,3-DPG or the glucose level.

Experimentally produced sinusoidal fetal heart rate pattern in the chronically instrumented fetal lamb.

A sinusoidal fetal heart rate and elevated fetal arginine vasopressin levels were found in two bled fetal lambs. Arginine vasopressin was continuously infused intravenously in chronically instrumented fetal lambs at rates ranging between 1.0 and 90 mlU/kg/min. No sinusoidal heart rate occurred in 21 experiments on six control animals with intact vagal nerves. Atropine at doses less than 0.4 mg had no effect (six experiments on three animals). Higher doses of atropine (greater than 1.2 mg) resulted in sinusoidal heart rate (24 experiments on six animals). Twenty-three infusions were performed in five bilaterally vagotomized fetuses, and the sinusoidal heart rate was successfully induced in 17 experiments. The arginine vasopressin infusion rate was less than 1.5 mlU/kg/min on the six occasions in which the sinusoidal heart rate did not appear. All sinusoidal heart rate patterns were associated with fluctuation of fetal arterial pressure at the same frequency. There was a linear correlation between the amplitude of sinusoidal heart rate and magnitude of arterial blood pressure fluctuation. The amplitude of sinusoidal heart rate increased with the concentration of arginine vasopressin infused. Modification of sinusoidal heart rate pattern was attempted with use of sympathetic agonists and antagonists. The possible etiology and mechanisms of sinusoidal heart rate pattern are discussed.