The effect of acute maternal hypoxia on fetal oxygenation and the umbilical circulation in the sheep

The mean oxygen consumption was 8.4 ± 1.9 ml/min/kg in the near-term fetal sheep. In response to acute maternal hypoxia fetal O₂ consumption decreased to lower than 50% of the control values. The decrease was rapidly instituted, proportional to the degree of hypoxia, sustained for up to 47 min and stable over this period. With increasing duration of hypoxia, a progressive metabolic acidosis developed. Recovery of oxygen consumption occurred rapidly after hypoxia ceased, though the acidosis was not resolved until 2 h later. Umbilical blood flow was maintained during maternal hypoxia and umbilical arterial and venous pressures increased. A fetal bradycardia invariably accompanied the hypoxia.     

Effect of parasympathetic and beta-adrenergic blockade on the umbilical circulation in the unanesthetized fetal sheep.

Parasympathetic and beta-adrenergic blocking agents were administered to near term chronically instrumented sheep. Parasympathetic blockade resulted in a significant increase in fetal heart rate and fetal arterial blood pressure, with a minimal nonsignificant increase in umbilical blood flow. beta-Adrenergic blockade resulted in a decrease in fetal heart rate and umbilical blood flow, though neither was statistically significant. There was no change in arterial blood pressure. The net result of parasympathetic and beta-adrenergic blockade on fetal heart rate suggests that the intrinsic rate is the same as when these influences are present.     

The PR interval-fetal heart rate relationship during repetitive umbilical cord occlusions in immature fetal sheep

OBJECTIVE: To evaluate the relationship of the PR interval and fetal heart rate during repetitive umbilical cord occlusions in immature sheep fetuses. STUDY DESIGN: In seven chronically cannulated immature sheep fetuses [gestational age 90.6 days (mean)], we analyzed continuous fetal electrocardiogram recordings during repetitive cord occlusions for 2 out of every 5 min until fetal mean arterial pressure dropped to 50% of baseline value. PR interval-fetal heart rate correlation coefficients (Pearson) was measured on consecutive blocks of 2.5 min. R-values of the baseline and the repetitive occlusion period were compared by Fisher's exact test. RESULTS: Repetitive cord occlusions resulted in acidosis and hypotension. Two fetuses died at the end of the repetitive occlusion period. Four out of seven fetuses showed a significant change from a negative relationship between the PR interval and fetal heart rate during baseline to a predominantly positive relationship during the repetitive occlusion period. CONCLUSION: In immature fetal sheep, a change from a negative relationship between the PR interval and fetal heart rate to a predominantly positive relationship between the PR interval and fetal heart rate was observed in four out of seven fetuses following the initiation of repetitive umbilical cord occlusions.     

The slope of fetal heart rate deceleration is predictive of fetal condition during repeated umbilical cord compression in sheep

The relationship between components of fetal heart rate deceleration and fetal arterial blood gas values or plasma catecholamine concentrations was investigated by repeated complete umbilical cord compression in chronically instrumented fetal lamb. Fetal arterial pH and bicarbonate levels decreased, while plasma norepinephrine and epinephrine concentrations increased more than tenfold. The slope of the descending limb of the fetal heart rate deceleration curve decreased and correlated strongly with fetal arterial pH, bicarbonate, and logarithmic plasma norepinephrine and epinephrine concentrations. Fetal arterial pH and bicarbonate levels were significantly lower in the group with lower fetal heart rate deceleration slope, and a greater plasma catecholamine concentration in this group suggested a redistribution of blood flow to vital organs. Therefore, during repeated umbilical cord compression, the fetal acid-base and hormonal state was predicted by the fetal heart rate deceleration slope. This relationship may be applicable to human fetuses in the diagnosis of fetal distress caused by umbilical cord compression during labor.     

The influence of spontaneous accelerations of fetal heart rate on umbilical artery velocity waveforms

For clinical interpretation of Doppler waveforms, it is important to establish the extent to which fetal heart rate changes affect the umbilical artery velocity waveform. Umbilical artery waveforms were measured with continuous wave ultrasonography during spontaneous accelerations of the fetal heart rate in 20 uncomplicated, near-term pregnancies. On average, an acceleration of 20 beats/min of fetal heart rate within an individual was associated with a reduction in the systolic/diastolic velocity ratio of 0.25. There was, however, considerable variability in the response, and in six patients the systolic/diastolic ratio actually increased with heart rate. We conclude that fetal heart accelerations within the normal range cause only small and variable changes in the systolic/diastolic ratio.     

Increased fetal heart rate variability with acute hypoxia in chronically instrumented sheep

Fetal heart rate (FHR) and oxygen consumption were determined in 45 studies in 20 chronically instrumented, normoxic sheep. FHR variability was measured by a template device to determine amplitude range, and oscillatory frequency was manually counted over 5-min periods. During 26 min of isocapnic hypoxia, fetal O₂ consumption decreased 39% and FHR decreased 18%, and FHR variability increased, the changes being maintained over the treatment period. It is suggested that the maintenance of FHR variability during this profound hypoxia denotes adequate cardiorespiratory compensatory mechanisms during the short period; prolongation of the hypoxia would probably result in fetal cerebral or myocardial decompensation, and disappearance of FHR variability. The increased variability may be due to increased α-adrenergic activity.     

The effect of carotid sinus denervation on fetal heart rate variation in normoxia, hypoxia and post-hypoxia in fetal sheep

Objective To investigate whether carotid sinus nerve reflexes are linked to the increase in heart rate variation in acute (one hour) hypoxia in late gestation fetal sheep
Design Comparison of short term variation between intact and carotid sinus denervated fetuses in normoxia, hypoxia and post-hypoxia.
Subjects Sixteen chronically catheterised pregnant sheep in late gestation.
Results There was no significant difference in short term variation between intact and denervated fetuses in normoxia. In intact fetuses short term variation increased significantly in hypoxia. In denervated fetuses it tended to increase in hypoxia, but this was not statistically significant. During the post-hypoxia period, short term variation increased significantly in denervated fetuses, although at this time it was decreasing in intact fetuses. When the decrease in pH was small intact fetuses showed a significantly greater increase in short term variation than denervated fetuses in hypoxia. In contrast, short term variation increased similarly in both groups when the pH decrease was greater (> 0.03 in early hypoxia and > 0.05 in late hypoxia).
Conclusions Carotid sinus nerve reflexes have an important influence on heart rate variation in hypoxia and post-hypoxia. It appears that other mechanisms (e.g. a rise in circulating catecholamines) are linked to an increase in heart rate variation when mild acidemia occurs in hypoxia.     

Fetal heart rate variability changes during brief repeated umbilical cord occlusion in near term fetal sheep.

OBJECTIVE: To determine whether changes in fetal heart rate variation during repeated umbilical cord occlusions reflect evolving cardiovascular compromise in near term fetal sheep. DESIGN: Fetal heart rate variation, fetal mean arterial pressure, electroencephalogram (EEG) and acid-base status were measured during one minute umbilical cord occlusions, repeated either every five minutes (1:5 group) or every 2.5 minutes (1:2.5 group) for four hours or until mean arterial pressure fell below 20 mmHg for two successive occlusions. SAMPLE: Fourteen chronically instrumented fetal sheep, mean gestation 126.3 (2.6) days. RESULTS: Cord occlusion caused variable decelerations with initial sustained hypertension. In the 1:5 occlusion group mean arterial pressure remained elevated throughout, with little change in acid-base status (pH = 7.34 (0.07), base deficit = 1.3 (3.9) after 4 hours) and no significant change in fetal heart rate variation. In contrast, in the 1:2.5 group from the third occlusion there was progressive hypotension during occlusions, severe progressive metabolic acidaemia (pH 6.92 (0.1), base deficit 17.0 mmol/L (4.7) after the last occlusion) and marked EEG suppression (P < 0.01). Fetal heart rate variation increased with the onset of occlusions (P < 0.05) and then progressively fell with continued occlusions. During the last 30 minutes of occlusions, fetal heart rate variation was severely suppressed in four, but increased in two fetuses, while all six fetuses developed overshoot-instability of fetal heart rate and mean arterial pressure following each occlusion. CONCLUSIONS: Acute progressive asphyxia was typically associated with an immediate, transient increase in fetal heart rate variation. Subsequently variation became suppressed in only two-thirds of fetuses during terminal acidaemia and hypotension. Fetal heart rate overshoot-instability may be a useful marker of fetal decompensation following variable decelerations.     

Fetal heart rate overshoot during repeated umbilical cord occlusion in sheep

OBJECTIVE: To assess the clinical utility of overshoot fetal heart rate (FHR) decelerations by examining their occurrence after umbilical cord occlusions of varying frequency and length in near-term fetal sheep. METHODS: Fetuses were allocated to the following three groups: 1-minute umbilical cord occlusion repeated every 5 minutes (1:5 group, n = 8) or every 2.5 minutes (1:2.5 group, n = 8) or 2-minute occlusions repeated every 5 minutes (2:5 group, n = 4). Occlusions were continued for 4 hours or until fetal mean arterial pressure decreased below 20 mmHg during two successive occlusions. RESULTS: In the 1:5 group, fetuses tolerated 4 hours of occlusion without hypotension or clinically significant acidosis and overshoot never occurred. In the 2:5 group, fetuses rapidly became hypotensive and acidotic, and occlusions were terminated at 116.3 +/- 22.9 min (mean +/- standard deviation). Overshoot was seen after every occlusion, starting with the first occlusion. In the 1:2.5 group, fetuses became progressively acidotic and hypotensive and occlusions were stopped at 183.1 +/- 42.8 min. Overshoot occurred after 91.6 +/- 42.5 minutes, at a pH of 7.17 +/- 0.06, base deficit 9.3 +/- 4.5 mmol/L. After the appearance of overshoot there was a more rapid decrease in fetal mean arterial pressure (0.25 [0.21, 0.35, 25-75th percentile] mmHg/minute versus 0.11 [0.03, 0.15] mmHg/minute before overshoot appeared, P <.01). CONCLUSION: These data suggest that overshoot is related to longer (2-minute) occlusions or to developing fetal acidosis and hypotension during 1-minute occlusions. This pattern could have clinical utility, as 1-minute contractions are typical of active labor.     

Redistribution of power spectrum of heart rate variability during acute umbilical artery embolism and hypoxemia in late-gestation fetal sheep

OBJECTS: Fetal heart rate variability (HRV) is subject to a number of factors, including fetal distress. The aim of this study was to investigate the power spectral distribution of fetal heart rate variability during acute hypoxemia following umbilical artery embolism and to test the hypothesis that the relative proportion of frequency domains in total power of HRV, reflects the changes in HRV during hypoxemia more closely than the absolute values. METHODS: Acute hypoxemia was induced in seven catheterized late-gestation fetal sheep by repeated injections of microspheres to cause umbilical artery embolism. The very-low, low-, middle- and high-frequency domains (0-0.025, 0.025-0.125, 0.125-0.20, and 0.20-0.50 cycles/beat, respectively) were determined by power spectral analysis. RESULTS: Umbilical artery embolism induced marked fetal hypoxemia, hypercapnia and acidosis, accompanied by an increase in heart rate and a decrease in arterial blood pressure. These changes were associated with the increase in power over the entire frequency range and in the relative power in the low-frequency range (P<0.01), and with decrease in the relative power in the high-frequency range (P<0.05). Correlations were found between the relative power in the low- and high-frequency ranges and PO2 and between the relative power in these ranges and mean arterial blood pressure (P<0.05), but not PCO2 or pH. CONCLUSIONS: The present study indicates that acute hypoxemia induced by umbilical artery embolism leads to the redistribution of power spectral density of fetal HRV and that the relative proportion of individual frequency domains may reflect the changes in HRV during acute hypoxemia more closely than the absolute power values.     

Effect of angiotensin infusion during pregnancy on fetal heart rate and on fetal activity

The angiotensin sensitivity test is of value in predicting patients at increased risk of pregnancy-induced hypertension and preeclampsia. Studies on the effects of angiotensin II on uterine blood flow in various species showed contradicting results. In the present study, 15 pregnant women were monitored by cardiotocography before, during and after an infusion of angiotensin II-amide (maximal infusion rates 6.3–23.2 ng · kg^?1 · min^?1). No remarkable changes in fetal heart rate, oscillatory frequency and amplitude, as well as in the number of accelerations and fetal movements could be observed. It may be concluded from these results that the fetal condition is not compromised by an angiotensin sensitivity test.     

The effect of fetal heart rate on umbilical artery flow velocity waveforms

Umbilical artery flow velocity waveforms were obtained using continuous wave Doppler ultrasound in 85 normal pregnancies (25 antepartum, 60 intrapartum) to examine the relation between fetal heart rate, end systolic/end diastolic ratio (A/B ratio) and resistance index (RI). Our results demonstrated a significant negative correlation between fetal heart rate, A/B ratio and RI (in the antepartum group r = -0.49, and in the labouring group r = -0.65). It is therefore important when performing mathematical analysis of umbilical artery flow velocity profiles to make a statistical allowance for fetal heart rate.     

Power spectral analysis of heart rate variability during acute hypoxia in fetal lambs

BACKGROUNDS: The aim of the current study was to investigate the changes in the power spectral pattern of the heart rate variability of fetal lambs during acute hypoxia and the possible value of power spectral analysis as a quantitative fetal monitoring method. METHODS: Acutely instrumented eight fetal lambs in the third trimester of gestation were subjected to reproducible hypoxia by reducing the maternal placental blood flow with complete obstruction of the maternal abdominal aorta for 60 s. Fetal electrocardiographic data 5 min prior to occlusion, 1 min during occlusion and 1, 5, and 10 min after the removal of occlusion were analyzed using power spectral analysis. Differences among the procedural steps were determined by the Friedman test with multiple comparisons using Duncan's multiple-range test. Wilcoxon's rank sum test was used for the comparison between low-and high-frequency power values at each step. p< 0.05 was considered significant. RESULTS: Low-, high-, total-frequency power and low-to-high frequency ratio all significantly increased with hypoxia compared with the baseline state (p < 0.05). High-frequency power remained higher than low-frequency power during the resting state (baseline state, 5 and 10 min after hypoxia). CONCLUSIONS: Increased low-frequency power and low-to-high frequency ratio during hypoxia reflects increased sympathetic activity compared with the baseline state. Higher high-frequency power during the resting state compared with low-frequency power reflects active respiratory movement of the fetal lambs near term and increased parasympathetic activity. It appeared possible that power spectral analysis could serve as a useful quantitative tool to monitor the autonomic changes in fetal lambs during hypoxia.     

Effect of acute hypoxia on human fetal heart rate. The significance of increased heart rate variability

The fetal heart rate response to acute hypoxemia was observed during an accidental drop in oxygen concentration inspired by the mother in labor. There was a marked increase in FHR variability in the early stage of hypoxia and also during the recovery phase. While an increase in fetal heart variability is generally considered to be a normal physiological event, it may also indicate a state of fetal hypoxemia associated with an intact fetal circulation, and should be treated with caution during labor.     

Fetal seizures causing increased heart rate variability during terminal fetal hypoxia.

Fetal seizures together with both abnormal breathing movements and fluctuations in fetal blood pressure and heart rate resulting in increased fetal heart rate variability have been observed in brain-damaged fetal sheep shortly after an asphyxial insult. We report a clinical example of convulsions and increased heart rate variability during terminal fetal hypoxia.     

Fetal heart rate variability and cerebral oxygen consumption in fetal sheep during asphyxia.

This study was designed to examine the relationship between fetal heart rate variability and fetal cerebral oxygen uptake. Fetal sheep were chronically prepared with catheters and electrodes to determine cerebral blood flow (microsphere method), cerebral arteriovenous oxygen difference, and the electrocardiogram. An adjustable occluder was placed on the maternal common internal iliac artery to induce fetal asphyxia by reducing uterine blood flow. Fetal heart rate variability tended to decrease in the first 11 min of asphyxia, when cerebral oxygen consumption was approximately 53% of control. Despite stable cerebral oxygen consumption and worsening metabolic acidosis, however, fetal heart rate variability progressively returned towards normal by 36 min. There was no relationship between the depression of FHR variability and the degree of reduction of cerebral oxygen consumption. Nor was there any relationship between an alteration in regional cerebral blood flow or myocardial blood flow and the return of FHR variability with increasing duration of asphyxia. We conclude that there is an association between loss of fetal heart rate variability and reduced cerebral oxygen consumption, but the reduced variability does not persist with time at this degree of reduced cerebral metabolism in fetal sheep. This appears to be at variance with human clinical experience. Among the explanations for this may be insufficiently severe asphyxia, a species difference, removal of an inhibitor to FHR variability, or progressive use of other substrates for metabolism.