Fetal Mean Arterial Blood Pressure Research Articles

Deceleration area and capacity during labour-like umbilical cord occlusions identify evolving hypotension: a controlled study in fetal sheep.

Cardiotocography is widely used to assess fetal well-being during labour. The positive predictive value of current clinical algorithms to identify hypoxia-ischaemia is poor. In experimental studies, fetal hypotension is the strongest predictor of hypoxic-ischaemic injury. Cohort studies suggest that deceleration area and deceleration capacity of the fetal heart rate trace correlate with fetal acidaemia, but it is not known whether they are indices of fetal arterial hypotension. Prospective, controlled study. Laboratory. Near-term fetal sheep. One minute of complete umbilical cord occlusions (UCOs) every 5minutes (1:5min, n=6) or every 2.5minutes (1:2.5min, n=12) for 4hours or until fetal mean arterial blood pressure fell <20mmHg. Deceleration area and capacity during the UCO series were related to evolving hypotension. The 1:5min group developed only mild metabolic acidaemia, without hypotension. By contrast, 10/12 fetuses in the 1:2.5-min group progressively developed severe metabolic acidaemia and hypotension, reaching 16.8±0.9mmHg after 71.2±6.7 UCOs. Deceleration area and capacity remained unchanged throughout the UCO series in the 1:5-min group, but progressively increased in the 1:2.5-min group. The severity of hypotension was closely correlated with both deceleration area (P<0.001, R2 =0.66, n=18) and capacity (P<0.001, R2 =0.67, n=18). Deceleration area and capacity predicted development of hypotension at a median of 103 and 123minutes before the final occlusion, respectively. Both deceleration area and capacity were strongly associated with developing fetal hypotension, supporting their potential to improve identification of fetuses at risk of hypotension leading to hypoxic-ischaemic injury during labour. Deceleration area and capacity of fetal heart rate identify developing hypotension during labour-like hypoxia.

Fetal cardiovascular response to acute hypoxia during maternal anesthesia.

Preclinical imaging studies of fetal hemodynamics require anesthesia to immobilize the animal. This may induce cardiovascular depression and confound measures under investigation. We compared the impact of four anesthetic regimes upon maternal and fetal blood gas and hemodynamics during baseline periods of normoxia, and in response to an acute hypoxic challenge in pregnant sheep. Merino ewes were surgically prepared with maternal and fetal vascular catheters and a fetal femoral artery flow probe at 105–109 days gestation. At 110–120 days gestation, ewes were anesthetized with either isoflurane (1.6%), isoflurane (0.8%) plus ketamine (3.6 mg·kg−1·h−1), ketamine (12.6 mg·kg−1·h−1) plus midazolam (0.78 mg·kg−1·h−1), propofol (30 mg·kg−1·h−1), or remained conscious. Following 60 min of baseline recording, nitrogen was administered directly into the maternal trachea to displace oxygen and induce maternal and thus fetal hypoxemia. During normoxia, maternal PaO2 was ~30 mmHg lower in anesthetized ewes compared to conscious controls, regardless of the type of anesthesia (p < .001). There was no effect of anesthesia on fetal mean arterial blood pressure (MAP; p > .05), but heart rate was 32 ± 8 bpm lower in fetuses from ewes administered isoflurane (p = .044). During maternal hypoxia, fetal MAP increased, and peripheral blood flow decreased in all fetuses except those administered propofol (p < .05). Unexpectedly, hypoxemia also induced fetal tachycardia regardless of the anesthetic regime (p < .05). These results indicate that despite maternal anesthesia, the fetus can mount a cardiovascular response to acute hypoxia by increasing blood pressure and reducing peripheral blood flow, although the heart rate response may differ from when no anesthesia is present.

Acute on chronic exposure to endotoxin is associated with enhanced chemoreflex responses in preterm fetal sheep

There is increasing evidence that exposure to infection can sensitize the fetus to subsequent hypoxic injury. However, it is unclear whether this involves compromise of the fetal cardiovascular adaptation to acute asphyxia. Chronically instrumented 103-day-old (0.7 gestational age, term is 147 days) fetal sheep in utero were randomized to receive either gram-negative lipopolysaccharide (LPS) as a continuous low-dose infusion for 120 h plus boluses of 1 μg LPS at 48, 72, and 96 h with asphyxia at 102 h (i.e., 6 h after the final LPS bolus) induced by umbilical cord occlusion for 15 min (LPS treated, n = 8), or the same volume of saline plus occlusion (saline treated, n = 7). Fetuses were killed 5 days after occlusion. LPS was associated with a more rapid fall in fetal heart rate at the onset of occlusion (P < 0.05) and with minimally lower values during occlusion (P < 0.05). The LPS-treated fetuses had lower fetal mean arterial blood pressure (BP) and greater carotid artery blood flow (CaBF) before occlusion (P < 0.05) but showed an increase in BP and fall in CaBF to similar values as saline controls during occlusion. There were no differences between the groups in femoral blood flow before or during occlusion. Contrary to our initial hypothesis, acute on chronic exposure to LPS was associated with more rapid cardiovascular adaptation to umbilical cord occlusion.

A fetal goat model of cardiopulmonary bypass with cardioplegic arrest and hemodynamic assessment

Increasing evidence shows that some cardiac defects may benefit from fetal interventions, including fetal cardiac surgery. We attempted to develop an invivo animal model of fetal cardiopulmonary bypass with cardioplegic arrest. Operations were performed on 14 pregnant goats. The extracorporeal circulation circuit consisted of a centrifugal pump, silicone tubings with an inner diameter of 6 mm, a roller pump, and a reservoir. The placenta was the sole oxygenator. Cardiopulmonary bypass was maintained at a mean flow rate of 344 ± 68 mL/kg/min, including 30 minutes of cardiac arrest and 15 minutes of reperfusion. Mean arterial blood pressure and heart ratewere monitored. Arterial blood samples were analyzed. The pulse index and resistance index of the fetal umbilical artery were monitored. Experiments were completed in 11 cases (79%), with the fetuses weighing 0.65 to 1.8 kg. Fetal mean arterial blood pressure and heart rate remained stable throughout the experiments. A decrease in partial pressure of oxygen with concomitant increase in carbon dioxide partial pressure was noted, but trends were relatively stable. Metabolic acidosis was recognized during and after cardiac bypass. The pulse index and resistance index of the umbilical artery increased significantly after 2 hours off bypass. We confirmed the technical feasibility of establishing an invivo model of fetal cardiac bypass with cardioplegic arrest. This fetal goat model provides reproducible data and is suitable to study clinically relevant problems related to fetal cardiopulmonary bypass, myocardial protection, and hemodynamics.

Different Responses of Myocardial and Cerebral Blood Flow to Cord Occlusion in Exteriorized Fetal Sheep

Type and duration of fetal asphyxial insult affect the distribution of blood flow to the heart and brain. The purpose of this study was to describe dynamic and quantitative changes in regional myocardial and cerebral blood flow (CBF) during fetal asphyxia induced by total occlusion of the umbilical cord. Eleven exteriorized fetal sheep were subjected to total umbilical cord occlusion and five fetal sheep served as sham controls. Regional blood flow (BF) to the brain and heart was quantified using radioactive microspheres before and after 5 min of occlusion and finally when fetal mean arterial blood pressure had decreased below 25 mm Hg, 9.8 (0.8) [mean (SD)] min after occlusion. Right coronary arterial (RCA) blood flow velocity and carotid BF were registered continuously. Mean values of arterial pH and oxygen content (mL O(2)/100 mL) were 7.08 (0.11) and 4.4 (2.9) before cord occlusion and decreased to 6.83 (0.05) and 1.4 (0.9) at 5 min after occlusion (p < 0.01, respectively). Carotid BF was significantly below preocclusion values by 2.5 min (p < 0.05), whereas RCA velocity time integral per minute remained above preocclusion values for 9 min. CBF decreased from 316 (24) before cord occlusion to 156 (30) mL/min/100 g at 5 min (p < 0.01), whereas right myocardial BF was maintained at 792 (125) and 751 (183) mL/min/100 g, respectively. CBF decreased rapidly after total cord occlusion whereas myocardial BF increased and was maintained until shortly before cardiac arrest, suggesting the myocardium to be better preserved during this type of insult in already partially asphyxiated fetuses.

The effect of intrafetal infusion of metyrapone on arterial blood pressure and on the arterial blood pressure response to angiotensin II in the sheep fetus during late gestation.

While the impact of exogenous glucocorticoids on the fetal cardiovascular system has been well defined, relatively few studies have characterised the role of endogenous fetal glucocorticoids in the regulation of arterial blood pressure (BP) during late gestation. We have therefore infused metyrapone, an inhibitor of cortisol biosynthesis, into fetal sheep from 125 days gestation (when fetal cortisol concentrations are low) and from 137 days gestation (when fetal cortisol concentrations are increasing) and measured fetal plasma cortisol, 11-desoxycortisol and ACTH, fetal systolic, diastolic and mean arterial BP, heart rate, and the fetal BP responses to increasing doses of angiotensin II (AII). At 125 days gestation, there was a significant increase in fetal plasma ACTH and 11-desoxycortisol by 24 h after (+24 h) the start of the metyrapone infusion, and plasma cortisol concentrations were not different at +24 h when compared with pre-infusion values. Whilst the initial fall in circulating cortisol concentrations may have been transient, systolic, diastolic and mean arterial BP were ~5-6 mmHg lower (P < 0.05) in metyrapone- than in vehicle-infused fetuses at 24-48 h after the start of the infusion. When metyrapone was infused from 137/138 days gestation, there was a significant decrease in plasma cortisol concentrations by +6 h, which was followed by an increase back to pre-infusion values. While cortisol concentrations decreased, there was no change in fetal mean arterial BP during the first 24 h after the start of metyrapone infusion. Mean fetal arterial BP values at 137-139 days gestation were not different in fetuses that had been infused with either vehicle or metyrapone from 125 days gestation or with metyrapone from 137/138 days gestation. At 137-139 days gestation, however, arterial BP responses to increasing doses of AII were significantly blunted in fetuses that had been infused with metyrapone from 125 days gestation, when compared with fetuses that had been infused with metyrapone from 137/138 days gestation or with vehicle from 125 days gestation. The dissociation of the gestational age increase in arterial BP and the effects of intrafetal AII on fetal arterial BP indicates that increase in fetal BP with gestational age is not entirely a result of an increased vascular responsiveness to endogenous AII. Furthermore there may be a critical window during late gestation when the actions of cortisol contribute to the development of vascular responsiveness to AII.

The effect of intrafetal infusion of metyrapone on arterial blood pressure and on the arterial blood pressure response to angiotensin II in the sheep fetus during late gestation

While the impact of exogenous glucocorticoids on the fetal cardiovascular system has been well defined, relatively few studies have characterised the role of endogenous fetal glucocorticoids in the regulation of arterial blood pressure (BP) during late gestation. We have therefore infused metyrapone, an inhibitor of cortisol biosynthesis, into fetal sheep from 125 days gestation (when fetal cortisol concentrations are low) and from 137 days gestation (when fetal cortisol concentrations are increasing) and measured fetal plasma cortisol, 11-desoxycortisol and ACTH, fetal systolic, diastolic and mean arterial BP, heart rate, and the fetal BP responses to increasing doses of angiotensin II (AII). At 125 days gestation, there was a significant increase in fetal plasma ACTH and 11-desoxycortisol by 24 h after (+24 h) the start of the metyrapone infusion, and plasma cortisol concentrations were not different at +24 h when compared with pre-infusion values. Whilst the initial fall in circulating cortisol concentrations may have been transient, systolic, diastolic and mean arterial BP were ∼5–6 mmHg lower (P < 0.05) in metyrapone- than in vehicle-infused fetuses at 24–48 h after the start of the infusion. When metyrapone was infused from 137/138 days gestation, there was a significant decrease in plasma cortisol concentrations by +6 h, which was followed by an increase back to pre-infusion values. While cortisol concentrations decreased, there was no change in fetal mean arterial BP during the first 24 h after the start of metyrapone infusion. Mean fetal arterial BP values at 137–139 days gestation were not different in fetuses that had been infused with either vehicle or metyrapone from 125 days gestation or with metyrapone from 137–138 days gestation. At 137–139 days gestation, however, arterial BP responses to increasing doses of AII were significantly blunted in fetuses that had been infused with metyrapone from 125 days gestation, when compared with fetuses that had been infused with metyrapone from 137/138 days gestation or with vehicle from 125 days gestation. The dissociation of the gestational age increase in arterial BP and the effects of intrafetal AII on fetal arterial BP indicates that increase in fetal BP with gestational age is not entirely a result of an increased vascular responsiveness to endogenous AII. Furthermore there may be a critical window during late gestation when the actions of cortisol contribute to the development of vascular responsiveness to AII.

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage

Objectives: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. Study design: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO2, base excess, oxygen saturation (SatO2), and PO2 were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. Results: Our data showed severe ischemia (CaF: 10 ± 7 mL/min; FMABP: 29 ± 8 mm Hg) and acidemia (pH: 7.0 ± 0.05; base excess: −9.9 ± 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. Conclusion: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion. (Am J Obstet Gynecol 2003;188:413-8.)

Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation.

This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 +/- 1 dGA, fetuses were infused with dexamethasone (2.06 +/- 0.13 microg kg(-1) h(-1) i.v.; n = 13) or saline (n = 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 +/- 1 (pre-infusion), 126 +/- 1 (during infusion) and 128 +/- 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 +/- 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 +/- 0.12 mmHg (ml min(-1))(-1) (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment.

Periconceptional nutrition programs development of the cardiovascular system in the fetal sheep.

It has been proposed that fetal adaptations to intrauterine nutrient deprivation permanently reprogram the cardiovascular system. We investigated the impact of restricted periconceptional nutrition and/or restricted gestational nutrition on fetal arterial blood pressure (BP), heart rate, rate pressure product, and the fetal BP responses to ANG II and the angiotensin-converting enzyme inhibitor captopril during late gestation. Restricted periconceptional nutrition resulted in an increase in fetal mean arterial BP between 115 and 125 days gestation (restricted 41.5 +/- 2.8 mmHg, n = 12; control 38.5 +/- 1.5 mmHg, n = 13) and between 135 and 147 days gestation (restricted 50.5 +/- 2.2 mmHg, n = 8; control 42.5 +/- 1.9 mmHg, n = 10) as well as an increase in the rate pressure product in twin, but not singleton, fetuses between 115 and 147 days gestation. Mean BP and fetal plasma ACTH were also positively correlated in twin, but not singleton, fetuses. This is the first demonstration that maternal undernutrition during the periconceptional period results in an increase in fetal arterial BP. This increase occurs concomitantly with an increase in fetal ACTH but is not dependent on activation of the fetal renin-angiotensin system.

The effect of repeated acute hypoxaemia on fetal cardiovascular development in the sheep.

1. Hypoxaemia during intrauterine life may be important in the development of cardiovascular diseases in later life. Thus it was the aim of this study to investigate the effect of repeated acute hypoxia on the cardiovascular development and growth of the fetus. 2. Fourteen fetal sheep (105-109 days gestational age) were instrumented with amniotic and vascular catheters, an electrocardiogram (ECG) electrode and a flow probe around the femoral artery. Seven animals were given repeated acute isocapnic hypoxaemia (Pa,O2 reduced to ca. 13 mmHg) for 1 h every day for 14 days and they were compared to seven animals which remained normoxic throughout with respect to fetal mean arterial blood pressure (MAP), fetal heart rate (FHR), and fetal baro- and chemoreflexes. 3. No differences were found between the two groups of fetuses in FHR, MAP, baro- or chemoreflexes, femoral blood flow, femoral vascular resistance or fetal growth. 4. Repeated acute hypoxaemia of a moderate degree over a period of 2 weeks in late gestation does not affect cardiovascular development or growth in the fetal sheep.

The adrenocorticotropic hormone and arginine vasopressin responses to hypercapnia in fetal and maternal sheep.

Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.

Concentration thresholds for fetal swallowing and vasopressin secretion.

In adults, plasma osmolality thresholds for hypernatremia-induced arginine vasopressin (AVP) secretion are similar or less than thresholds for stimulation of thirst. In the fetus, the thresholds for swallowing stimulation and AVP secretion have not been defined. Fetal swallowing and AVP secretory responses to hypertonic NaCl and urea were determined in six fetuses (130 +/- 1 1 days) chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyograms (EMG), an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15, 0.30, 0.45, 0.60, 0.75, and 0.90 M), administered at 2-min intervals. A swallow was defined as a coordinated time-sequence of fetal thyrohyoid, nuchal esophagus, and thoracic esophagus EMG activity. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) after four of five injections at each dose. During a 2-h control period swallowing averaged 25.0 +/- 10.1 ml/h and 39.4 +/- 14.6 swallows/h. The mean NaCl threshold concentration for swallowing stimulation was 0.56 +/- 0.06 M. Fetal plasma AVP (2.6 +/- 0.9 pg/ml) increased significantly at the maximum subthreshold (7.6 +/- 4.0 pg/ml) and the threshold NaCl concentration (8.2 +/- 4.0 pg/ml) that stimulated swallowing. On a subsequent day, equiosmolar urea injections increased plasma AVP (from 2.2 +/- 0.7 to 7.6 +/- 2.6 pg/ml) but had no effect on swallowing activity. Fetal mean arterial blood pressure increased after injections of threshold saline and urea concentrations. Fetal arterial blood osmolality and sodium concentration did not change during any study.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal swallowing: response to systemic hypotension

The fetal swallowing and endocrine responses to systemic hypotension were studied in five chronically instrumented ovine fetuses (125 +/- 2 days). Fetuses were prepared with bipolar electrodes inserted in the thyrohyoid muscle, nuchal esophagus, and thoracic esophagus, a flow probe surrounding the thoracic esophagus, and arterial and venous catheters. In response to an intravenous infusion of sodium nitroprusside, fetal mean arterial blood pressure decreased from 50.8 +/- 3.6 to 41.7 +/- 3.8 mmHg. Fetal plasma renin activity (5.0 +/- 1.4-25.1 +/- 10.3 ng.ml-1.h-1) and arginine vasopressin (5.6 +/- 4.5-26.3 +/- 21.0 pg/ml) increased, while fetal swallowing electromyogram activity (7.3 +/- 1.1-1.9 +/- 0.3 swallows/10 min) and esophageal flow (5.5 +/- 3.1-1.2 +/- 0.9 ml/10 min) significantly decreased during the nitroprusside infusion. These results indicate a suppression of fetal swallowing in response to systemic hypotension despite stimulation of the renin-angiotensin system.

Arterial oxygenation determines autoregulation of cerebral blood flow in the fetal lamb.

We examined autoregulation of cerebral blood flow (CBF) over the range of oxygen tension commonly observed in the chronic fetal lamb preparation. Seventeen animals were surgically prepared under general anesthesia for chronic in utero studies. Based on measured resting arterial PO2 and calculated % saturation 24-48 h after surgery, two groups were defined: a normoxic group of eight with saturation of 57% or higher (our laboratory normal for physiologically stable preparations) and an hypoxic group of nine with saturation less than 57%. Regional CBF was measured with radiolabeled 15-microns microspheres. Autoregulation of CBF was assessed by measuring the change in CBF when fetal mean arterial blood pressure (MABP) was acutely decreased and increased by withdrawal and reinfusion of fetal blood. In normoxic animals CBF was constant over an MABP range of 42-61 torr in all four areas of the brain examined: cerebral hemispheres, basal ganglia, cerebellum, and brain stem. In hypoxic animals CBF was pressure dependent in all areas over an MABP range of 46-73 torr, i.e., autoregulation was abolished. These studies demonstrate that the mechanism of autoregulation is functionally developed in the mature fetal lamb, but operationally dependent upon arterial oxygen concentration. Below a saturation of approximately 50-60% CBF varies directly with perfusion pressure.

Effects of angiotensin II on the blood flow and its distribution in fetal lambs.

We studied the effects of intravenous infusion of angiotensin II on the circulation of the fetus in lambs in utero through chronically maintained intravascular catheters. Angiotensin II infused in doses of 29-280 ng/min per kg fetal weight resulted in an increase in plasma angiotensin II from a control value of 87 +/- 17 to 341 +/- 129 (mean +/- SE) pg/ml; these levels are similar to those observed following hemorrhage in fetal lambs. Fetal mean arterial blood pressure increased from 46 +/- 2.0 to 56 +/- 2.7 torr and fetal heart rate increased from 172 +/- 6 to 189 +/- 6 beats/min, an effect which was not altered by beta-adrenergic or cholinergic blockade. Fetal cardiac output and its distribution were measured before and during infusion of angiotensin II by the radionuclide-labeled microsphere technique. Combined ventricular output increased significantly from 526 +/- 32 to 616 +/- 24 ml/min per kg fetal body weight. Angiotensin constricted the umbilical-placental circulation as well as the gastrointestinal, renal, and thyroidal vascular beds. Angiotensin increased blood flow to the myocardium and markedly increased blood flow to the pulmonary circulation. These studies indicate that angiotensin II, at the plasma levels achieved with moderate hemorrhage, has marked influences on the circulation. The renin-angiotensin system may be important in the fetal response to stress.

The dynamics of vasopressin release and blood volume regulation during fetal hemorrhage in the lamb fetus.

Summary: Experiments were performed on 11 long-term fetal lamb preparations (103–138 days of gestation) to investigate the sensitivity and relative responsiveness of the fetal volume receptors in modulating fetal plasma arginine vasopressin (pAVP) secretion and plasma renin activity (PRA) secretion during fetal hypovolemia and after fetal blood volume replacement. During fetal hemorrhage there were significant decreases (P < 0.05) in fetal hematocrit (34.7 ± 2.58 to 27.0 ± 1.64%), plasma proteins (3.14 ± 0.15 to 2.78 ± 0.19 g/100 ml), mean arterial blood pressure (MABP) (58.1 ± 2.59 to 52.2 ± 2.60 mmHg) and fetal arterial pH (7.38 ± 0.01 to 7.35 ± 0.01). A significant increase in fetal pAVP concentration from 0.73 ± 0.21 to 34.9 ± 10.04 μU/ml (P < 0.01) and fetal PRA from 4.78 ± 2.22 to 40.4 ± 18.31 ng/ml/hr (P < 0.05) was demonstrated at the peak of fetal hemorrhage. Two hr after correction of the fetoplacental blood volume, these values were back to base line levels. No change in either maternal pAVP or PRA was seen during fetal hemorrhage. When individual values for log pAVP and log PRA were plotted as a function of percent of fetoplacental blood volume removed the correlation coefficients were 0.82 and 0.60, respectively. A multiple regression analysis showed a high correlation of log pAVP and log PRA with the volume of blood removed and a low partial correlation with the fetal MABP. This suggests the decrease in fetal MABP was not the primary factor explaining the increase in pAVP and PRA during fetoplacental blood volume depletion. The data indicate that the fetal volume receptors for control of arginine vasopressin secretion are fully functional in the last trimester of gestation and suggests that fetal pAVP and PRA are released as an exponential function of the percent of fetoplacental blood volume depletion. Finally, an isosmotic water shift from the fetal interstitial space to the fetal vascular space is described during fetal hemorrhage.Speculation: It is suggested that a change in the equilibrium between the forces regulating fluid movement through the fetal capillary membranes, in accordance with Starling's principle, activates isosmotic water fluxes from the fetal interstitial space to the fetal vascular compartment counteracting the effects of fetal blood volume depletion. Therefore, the role of arginine vasopressin (AVP) release during fetal hemorrhage, if any, will be to act as a pressor substance helping to maintain fetal blood pressure. No major effect of AVP on placental membranes was demonstrated in vivo.

Cardiovascular effects of fever in the ewe and fetal lamb

Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1μg). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8° C. higher than maternal temperature rose in parallel with the ewe's temperature. During the matemal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function.