Threshold of hormonal and biophysical responses to acute hypoxemia in fetal sheep at different gestational ages

We examined whether there was a threshold for change in fetal arterial PO2 to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol, or to affect the incidence of fetal breathing movements or eye movements and we determined whether such a threshold changed with gestational age. Fetal sheep were exposed to two levels of hypoxemia, mild (4.6-5.3 mmHg PO2 drop) and moderate (8.3-8.8 mmHg PO2 drop) (1 mmHg = 133.322 Pa) for 1 h without pH change at 125-129 or 134-147 days of gestation within 7 days of spontaneous labor. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia at either age. In moderate hypoxemia at 125-129 days of gestation, there were significant increases of fetal adrenocorticotropic hormone, arginine vasopressin, and cortisol concentrations, and a decreased incidence of fetal breathing movements and eye movements. At 134-147 days of pregnancy, moderate hypoxemia induced a significant increase in adrenocorticotropic hormone, but the response was less than at 125-129 days of gestation. The arginine vasopressin response was similar to that at 125-129 days and there was no significant change in cortisol. There was a significant decrease in fetal breathing movements but not in eye movements. We conclude that a threshold of fetal arterial PO2 drop exists between 5 and 8 mmHg to elicit endocrine or biophysical responses to hypoxemia in fetal sheep at 125-129 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular responses to acute, severe haemorrhage in fetal sheep

In adults, the responses to acute haemorrhage vary greatly depending on the amount of blood lost. While many studies have documented fetal responses to mild haemorrhage, fetal responses to severe haemorrhage are not known. In this study we examined the effect of acute, severe haemorrhage in fetal lambs. Despite the severity of haemorrhage, we found that mean arterial blood pressure was restored within 2 min, and heart rate was restored within 30 min. This restoration of blood pressure and heart rate was facilitated by an increase in peripheral vascular resistance mediated in part by secretion of catecholamines and plasma renin. In addition, about 40% of the shed blood volume was restored within 30 min by fluid from either the fetal interstitium or placenta. The PO2 of umbilical venous blood increased from 33 +/- 9 mmHg to 49 +/- 17 mmHg 2 min post-haemorrhage, and to 47 +/- 15 mmHg 30 min post-haemorrhage. However, this increase was not sufficient to offset the fall in both haemoglobin concentration and umbilical-placental blood flow, so that oxygen delivery decreased from 21.1 +/- 5.5 ml/min per kg to 9.1 +/- 5.2 ml/min per kg 2 min post-haemorrhage, and 14.1 +/- 9.2 ml/min per kg 30 min post-haemorrhage. Because of this decrease in oxygen delivery, oxygen consumption fell and a metabolic acidemia ensued. Nevertheless, oxygen delivery to the heart and brain was maintained because hepatic vasoconstriction diverted more of the well oxygenated umbilical venous return through the ductus venosus. Although the fetus was able to tolerate acute loss of 40% of blood volume, larger volumes of haemorrhage resulted in fetal death.     

Fetal oxygen consumption and PO2 during hypercapnia in pregnant sheep

In 12 experiments on 9 chronically-cathetized pregnant sheep (116-143 days of gestation), fetal oxygen consumption, umbilical blood flow and blood gas values were measured before, during and after a 30-min period of hypercapnia, induced by having the ewes breathe 5% CO2 and 18% O2 in N2. During the large amplitude breathing stimulated by hypercapnia, O2 consumption increased by 21%, solely via a rise in O2 extraction. During apnoeic periods and low amplitude breathing in the hypercapnia period, oxygen consumption was not different from the control value, but fetal arterial and umbilical venous PO2 was significantly raised, by 3 and 6 mm Hg respectively. These changes were probably due to a Bohr shift in the maternal oxygen dissociation curve. During large amplitude breathing, PO2 fell to control levels, probably due in part to the increase in O2 extraction. It is concluded that vigorous breathing movements in the fetal sheep, such as those stimulated by hypercapnia, result to an increase in fetal O2 demands. Further, the work of such breathing is large, and probably equivalent to that performed in adults during vigorous hyperventilation against an inspiratory resistance.     

Increased oxygen consumption associated with breathing activity in fetal lambs

To examine the relationship between fetal O2 consumption and fetal breathing movements, we measured O2 consumption, umbilical blood flow, and cardiovascular and blood gas data before, during, and after fetal breathing movements in conscious chronically catheterized fetal lambs. During fetal breathing movements, O2 consumption increased by 30% from a control value of 7.7 +/- 0.7 (SE) ml X min-1 X kg-1. Umbilical blood flow was 210 +/- 21 ml X min-1 X kg-1 before fetal breathing movements; in 9 of 16 samples it increased by 52 +/- 12 ml X min-1 X kg-1, while in the other 7 it decreased by 23 +/- 9 ml X min-1 X kg-1. Umbilical arterial and venous O2 partial pressures and pH fell during fetal breathing movements, and the fall was greater when umbilical blood flow was decreased. Partial CO2 pressure rose in both vessels, and again the increase was greatest when umbilical blood flow fell during fetal breathing movements. Also associated with a fall in umbilical blood flow was the transition from low-amplitude irregular to large-amplitude regular fetal breathing movements. It is concluded that fetal breathing movements increase fetal O2 demands and are associated with a transient deterioration in fetal blood gas status, which is most severe during large-amplitude breathing movements.     

Fetal pulmonary vasodilation and vasoreactivity during metabolic acidaemia

We studied the pulmonary vascular response to progressive metabolic acidaemia and to an abrupt increase in oxygen tension during metabolic acidaemia in 8 chronically-prepared fetal sheep. Left pulmonary artery blood flow was measured by electromagnetic flow transducer. Two and a half hour infusion of NH4Cl into the fetal inferior vena cava caused pH to fall to 6.94 +/- 0.01 from 7.37 +/- 0.01 (P less than 0.001). During this period of progressive metabolic acidaemia, left pulmonary artery blood flow increased from a baseline value of 60 +/- 8 to 105 +/- 14 ml.min-1 (P less than 0.002). Pulmonary artery pressure did not change significantly and calculated pulmonary vascular resistance fell indicating fetal pulmonary vasodilation. PO2 rose significantly (19.8 +/- 0.7 to 24.1 +/- 1.8 torr; P less than 0.03) and oxygen saturation fell (54.6 +/- 2.8% to 38.9 +/- 3.5%; P less than 0.001) confirming a rightward shift of the oxyhaemoglobin dissociation curve. During acidaemia, administration of 100% oxygen to the ewe further increased fetal PO2 to 37.9 +/- 2.3 torr within 10 min (P less than 0.001) and this increase in PO2 was accompanied by an increase in left pulmonary artery blood flow (P less than 0.001), a fall in pulmonary artery pressure (P less than 0.03) and a decrease in pulmonary vascular resistance (P less than 0.001) indicating further vasodilation. The response of the fetal pulmonary circulation to a 2-h period of increased oxygen tension was qualitatively similar in acidaemic and non-acidaemic fetuses. We conclude that the progressive metabolic acidaemia imposed by these experimental conditions increases pulmonary blood flow likely through an increase in fetal PO2 and that metabolic acidaemia does not block the normal vasodilatory response to an increase in oxygen tension.     

Effects of severe reduction in maternal placental blood flow on blood flow distribution in the sheep fetus

To test the hypothesis that fetal lambs are able to maintain oxygen delivery to myocardial, brain and adrenal tissues during reduction in uterine blood flow to 25% of control, we performed experiments on five ewes and their fetuses. A snare occluder was placed around the maternal common hypogastric artery and catheters were placed for measurement of blood pressures, flows, blood gas tensions, pH and oxygen content. After a five day recovery period, control measurements were made. The snare occluder was then closed until the artery was fully occluded. The arterial occlusion caused uteroplacental blood flow to fall to 32 +/- 4% and maternal placental blood flow to fall to 25 +/- 3% of control values. This level of asphyxia was maintained for 19 +/- 3 minutes, when maternal and fetal blood flows were measured again. In response to occlusion, fetal ascending aortic PO2 fell from 21 +/- 2 (SEM) to 13 +/- 2 mmHg (P less than or equal to 0.01), oxygen content from 4.3 +/- 0.3 to 1.4 +/- 0.2 mM (P less than or equal to 0.01) and pH from 7.37 +/- 0.01 to 7.21 +/- 0.05 (P less than or equal to 0.01). PCO2 rose from 48 +/- 1 to 62 +/- 3 mmHg (P less than or equal to 0.01). Fetal arterial blood pressure increased from 51 +/- 3 to 61 +/- 3 mmHg (P less than or equal to 0.001) and heart rate decreased from 172 +/- 10 to 104 +/- 4 beats.min-1 (P less than or equal to 0.01). The heart, brain and adrenals showed vasodilation in response to the asphyxic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral oxidative metabolism during sustained hypoxaemia in fetal sheep

Cerebral oxidative metabolism was determined in 9 unanaesthetized fetal sheep near term, during a normoxic control period and during sustained hypoxaemia induced by lowering maternal inspired O2 concentration to 11-8% with 3% CO2 added. Preductal arterial and sagittal vein blood samples were analyzed for oxygen content, blood gas tensions and pH. Cerebral blood flow was measured with a radioactively-labelled microsphere technique. Induced fetal hypoxaemia resulted in a metabolic acidaemia which was progressive over several h. Cerebral oxygen consumption was initially marginally decreased in response to induced hypoxaemia with cerebral blood flow increased thus maintaining O2 delivery coupled to cerebral oxygen consumption. With a worsening metabolic acidemia, pHa below 7.15, cerebral blood flow fell as mean arterial pressure fell, but cerebral oxygen consumption was little changed as fractional O2 extraction now increased. With sustained hypoxaemia and profound metabolic acidaemia, pHa below 7.00, fractional O2 extraction also fell resulting in a terminal fall in cerebral oxygen consumption to less than 50% of control values. Although the initial marginal decrease in cerebral oxygen consumption in response to induced hypoxia may represent a protective mechanism whereby the fetal brain decreases nonessential functions thus lowering oxidative needs, the terminal fall in cerebral oxygen consumption suggests pathological alterations within the brain at this time.     

Response of pulmonary circulation to oral pirbuterol in chronic airflow obstruction.

The effects of the oral beta agonist pirbuterol on pulmonary haemodynamics and gas exchange were studied in nine patients with severe irreversible airflow obstruction and moderate arterial hypoxaemia. After administration of 15 mg pirbuterol pulmonary vascular resistance fell by 19% but cardiac output rose by 24%, so that pulmonary arterial pressure showed no significant change. Systemic arterial oxygen pressure fell by 7%, limiting the rise in oxygen delivery to 21%. All changes were significant at the 2% level. These results show that pirbuterol dilates the pulmonary bed at the cost of a slight worsening of gas exchange, which is compensated by an independent rise in blood flow.     

Oxygen consumption is maintained in fetal sheep during prolonged hypoxaemia.

Experiments were conducted in 12 chronically-catheterized pregnant sheep to examine the effect of prolonged hypoxaemia secondary to the restriction of uterine blood flow on fetal oxygen consumption. Surgery was performed at 115 days gestation to place a teflon vascular occluder around the maternal common internal iliac artery and for insertion of vascular catheters. Following a 5-day recovery period, uterine blood flow was reduced in 6 animals for 24 hours and in 6 animals, the occluder was not adjusted. Fetal arterial PO2 decreased from 19.9 +/- 2.0 mmHg to 12.8 +/- 2.0 mmHg and 11.0 +/- 2.0 mmHg at 1 and 24 hours respectively in the experimental group and did not change the control group. Fetal pH decreased from 7.34 +/- 0.01 to 7.25 +/- 0.03 and 7.29 +/- 0.02 at 1 and 24 hours of hypoxaemia respectively. Fetal arterial lactate concentrations remained elevated throughout the experimental period with maximum concentrations of 6.6 +/- 2.1 mmol/l being present at 4 hours compared to 1.3 +/- 0.2 mmol/l during the control period. Umbilical blood flow increased from 186 +/- 19 ml/min/kg to 251 +/- 39 ml/min/kg at 1 h of hypoxaemia and returned to 191 +/- 21 ml/min/kg at 24 h. In association with the progressive fall in oxygen delivery to the fetus, oxygen extraction increased from 0.33 +/- 0.04 to 0.43 +/- 0.04 and 0.54 +/- 0.05 at 1 and 24 hours, respectively. Overall oxygen consumption by the fetus remained unchanged from control values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hindlimb glucose and lactate metabolism during umbilical cord compression and acute hypoxemia in the late-gestation ovine fetus

The metabolic adaptation of the hindlimb in the fetus to a reversible period of adverse intrauterine conditions and, subsequently, to a further episode of acute hypoxemia has been examined. Sixteen sheep fetuses were chronically instrumented with vascular catheters and transit-time flow probes. In nine of these fetuses, umbilical blood flow was reversibly reduced by 30% from baseline for 3 days (umbilical cord compression), while the remaining fetuses acted as sham-operated, age-matched controls. Acute hypoxemia was subsequently induced in all fetuses by reducing maternal fractional inspired oxygen concentration for 1 h. Paired hindlimb arteriovenous blood samples were taken at appropriate intervals during cord compression and acute hypoxemia, and by using femoral blood flow and the Fick principle, substrate delivery, uptake, and output were calculated. Umbilical cord compression reduced blood oxygen content and delivery to the hindlimb and increased hindlimb oxygen extraction and blood glucose and lactate concentration in the fetus. However, hindlimb glucose and oxygen consumption were unaltered during umbilical cord compression. In contrast, hindlimb oxygen delivery and uptake were significantly reduced in all fetuses during subsequent acute hypoxemia, but glucose extraction, oxygen extraction, and hindlimb lactate output significantly increased in sham-operated control fetuses only. Preexposure of the fetus to a temporary period of adverse intrauterine conditions alters the metabolic response of the fetal hindlimb to subsequent acute stress. Additional data suggest that circulating blood lactate may be derived from sources other than the fetal hindlimb under these circumstances. The lack of hindlimb lactate output during acute hypoxemia in umbilical cord-compressed fetuses, despite a significant fall in oxygen delivery to and uptake by the hindlimb, suggests that the fetal hindlimb may not respire anaerobically after exposure to adverse intrauterine conditions. hypoxia     

Umbilical cord occlusion but not increased plasma T3 or norepinephrine stimulate brown adipose tissue thermogenesis in the fetal sheep

Nonshivering thermogenesis is normally inactive in utero but increases with supplemental oxygenation and again after occlusion of the umbilical cord. To test the hypothesis that brown fat responses are triggered by the surge in triiodothyronine (T3) which occurs at birth, we studied 7 fetal sheep at 132-143 days gestation. Fetuses were first cooled 2-3 degrees C by circulating cold water through an external coil in the amniotic fluid and then ventilated with oxygen in utero to raise arterial PO2 to 109 +/- 10 (SEM) mmHg. An hour later T3 was infused intravenously to elevate and maintain plasma levels at 39.8 +/- 6.1 nmol/l, some 40-50 times basal levels. Indices of brown heat production did not rise during the next 30 min. Following snaring of the umbilical cord, however, plasma free fatty acid levels increased 400% to 423 +/- 91 mEq/l, plasma glycerol rose 350% to 766 +/- 168 mmol/1, and the temperature difference between brown fat and body core widened to 0.59 +/- 0.13 degrees C during the next 30 min. Whole body oxygen consumption peaked at 23.1 +/- 2.8 ml.min-1.kg-1 body weight. These responses to cord occlusion were similar with and without T3 administration. Changes in plasma catecholamines during these experiments did not correlate with the onset of nonshivering thermogenesis. We conclude that the rise in T3 or the changes in plasma catecholamines which occurs at birth are not causally related to the onset of nonshivering thermogenesis.     

Hypoxia reduces oxygen consumption of fetal skeletal muscle cells in monolayer culture.

In a previous study on acute asphyxia in unanesthetized fetal sheep near term we showed that reduced oxygen delivery to peripheral organs reduces total oxygen consumption, suggesting that oxygen itself may be a determinant of oxygen consumption (Jensen, Hohmann & Künzel, 1987). To test this hypothesis we developed an in vitro perfusion model, which enabled us to measure the oxygen consumption of fetal skeletal muscle cells in monolayer culture in a control period (at approximately 145 mmHg) and during various degrees of hypoxia (6-140 mmHg). In 57 experiments on 57 cultures the mean oxygen consumption at a mean 'entry PO2' of 145.3 +/- 10.4 mmHg was 10.3 +/- 9.3 (SD).10(-6) microliters O2 per h per skeletal muscle cell. These measurements were made after an average of 4.2 +/- 2.3 transfers of the cells and at a cell density of 2.0 +/- 1.2.10(5) cells per cm2. In 54 of these experiments hypoxia was induced. There was a close positive correlation between the PO2 of the perfusate entering the Petridish ('entry PO2') and the change of the oxygen consumption of the cells (y = 5.17 - 0.54x + 0.03x2 - 0.00016x3, r = 0.97, p less than 0.0001). When oxygen tension fell, there was a concomitant fall in cellular oxygen consumption. We conclude that oxygen is a determinant of cellular oxygen consumption. Thus, hypoxia may reduce oxygen consumption of skeletal muscle cells, and oxygen may be preserved to maintain oxidative metabolism in central fetal organs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen supply and the placenta limit thermogenic responses in fetal sheep

The aim of this study was to assess the individual effects of cooling, increased oxygenation, and umbilical cord occlusion on nonshivering thermogenesis in utero. A cooling coil was placed around eight fetal sheep of 132-145 days gestation; thermistors were placed in the fetal esophagus and maternal iliac artery, vascular catheters and a tracheal catheter were inserted, and a snare was placed loosely around the umbilical cord. The next day cold water was circulated through the coil for 5 h. During the 1st h of cooling alone, fetal core temperature fell 2.79 degrees C, but indexes of brown fat activity increased only slightly. After ventilation with O2, plasma free fatty acid concentration (FFA) rose 7.4-fold to 244 +/- 42 mu eq/l, glycerol concentration rose fourfold to 376 +/- 85 microM, and the difference between brown fat and core temperature widened to 0.60 +/- 0.10 degrees C. Ventilation with N2-enriched air did not evoke similar responses. After snaring the umbilical cord while ventilation was continued, FFA rose to 554 +/- 95 mu eq/l, glycerol rose to 684 +/- 76 microM, and the temperature difference widened to 0.77 +/- 0.13 degrees C. Whole-body O2 consumption peaked at 19.6 ml.min-1.kg-1 of fetal tissue. We conclude that fetal thermogenic responses are limited in part by O2 delivery to brown fat and are augmented by occlusion of the umbilical cord.     

Changes in heart rate during progressive hyperoxia in the dogfish Scyliorhinus canicula L.: evidence for a venous oxygen receptor

Progressive hyperoxia caused a gradual increase in arterial blood oxygen tension (PaO2). Initially there was no change in venous O2 tension (PvO2) but in extreme hyperoxia (PO2 650 mmHg) it increased to 2.5 times the normoxic (PO2 150 mmHg) level (Table 1). Ventilation frequency gradually decreased down to 73% of the normoxic value as PO2 rose towards a maximum at 700 mmHg (Fig. 1). In moderately hyperoxic water (mean PO2 233 mmHg) heart rate (fH) increased significantly above the normoxic level. Further increases in ambient PO2 caused a progressive reduction in fH to a level significantly below the normoxic rate in extreme hyperoxia (Fig. 2). Injection of atropine abolished these changes, and the atropinized fH was similar to that measured during moderate hyperoxia. The initial increase in fH during progressive hyperoxia is attributed to release of vagal tone, due to removal of normoxic stimulation of peripheral oxygen receptors; whereas, the secondary bradycardia is attributed to the stimulation of oxygen receptors located in the venous system. Injection of 5 ml of hyperoxaemic blood into the venous system of normoxic fish caused a transient bradycardia (Fig. 3), lasting a mean of 73 sec, which is the approximate time for passage of the blood volume of the venous system through the heart. This bradycardia was neither pH dependent nor a pressor response and provides supporting evidence for the existence of a venous oxygen receptor.     

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep

To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial PO(2) (PaO(2)) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 microg. kg(-1). min(-1)) or the alpha(1)-adrenergic agonist phenylephrine (6.5 microg. kg(-1). min(-1)) into the umbilical vein or during hypoxemia (fetal Pa(O(2)) reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an alpha(1)-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV.     

Cardiac limitation to maximal oxygen transport and changes in components after jogging across the US.

Observations were made before and 3-5 days after prolonged endurance jogging an average of 42 miles/day, 6 days/wk for 2.5 mo by a young male adult who voluntarily initiated a run across the United States. Both arterial PO2 and lactic acid increased. In each instance, the first limitation in circulatory delivery of oxygen was a plateau in stroke volume and cardiac output. Afterward, pulse deficit and systemic arterial pressure fell with exercise and heart rate accelerated. Although there was no change in oxygen transport (Q X CAO2), a reduction in stroke volume was exactly balanced by a rise in arterial oxygen content. Vital capacity, residual volume, and total lung capacity and diffusion capacity for carbon monoxide, hematocrit, and red cell mass increased, while plasma volume diminished and heart size and total blood volume were unchanged.     

The effects of prostacyclin and thromboxane analogue (U46619) on the fetal circulation and umbilical flow velocity waveforms

In placental insufficiency and pre-eclampsia the relative production rates of prostacyclin and thromboxane by the placenta and umbilical vessels are altered and the Doppler umbilical flow velocity waveform shows a high resistance pattern. To investigate the control of umbilical placental blood flow by those eicosanoids either prostacyclin (10 micrograms/min), or the thromboxane analogue U46619 (10 ng/min) was infused into the distal aorta of 12 chronically catheterized fetal lambs at day 125. Thromboxane produced a rise in mean arterial pressure and a rise in the systolic diastolic ratio of the umbilical artery flow waveform (2.6 to 3.1; P less than 0.05). Umbilical blood flow did not change and there was no evidence of altered flow to other organs. Prostacyclin caused a fall in fetal mean arterial pressure and a decrease in the umbilical artery systolic diastolic ratio (2.9 to 2.4; P less than 0.05). Prostacyclin produced a three-fold increase in lung perfusion (and the onset of fetal breathing movements) and this was associated with a 90% reduction in muscle blood flow (hindlimb muscle flow reduced from 12.5 to 1.1 ml.min-1 100g-1; P less than 0.01). We conclude that the local release of thromboxane in the fetal placental vascular bed could account for the rise in systolic diastolic ratio seen in umbilical placental insufficiency.     

Serum cortisol level changes in the maternal-fetoplacental unit between the 28th-40th weeks of pregnancy

Changes in the serum cortisol level of maternal venous, umbilical venous and umbilical arterial blood were studied separately between the 28th-36th weeks in cases of preterm deliveries (n = 74) and in the 40th week in cases of term delivery (n = 34). Results indicate that between the 28th-40th weeks of pregnancy the cortisol concentration increased only in the serum of the umbilical artery; the "umbilical arterial/umbilical venous concentration X100" quotient rose from a value of 86% measured at 28th-32nd weeks to 103% in the 40th week of pregnancy. Positive correlation was found between the cortisol concentration of the three samples. On the basis of these results the authors believe that fetal adreno-cortical activity increases before birth.     

Cerebral metabolic and pressure-flow responses during sustained hypoxia in awake sheep.

Conscious sheep (n = 6), exposed to 3.5 h of normobaric hypoxia (arterial PO2 = 40 Torr) while allowed varying arterial PCO2, showed striking early increments of cerebral blood flow (CBF; +200-250%, by radiolabeled microspheres) and decrements of cerebral vascular resistance (CVR) in association with an early temporary elevation of cerebral O2 consumption (CMRO2; +25-60%). After 2 h, CMRO2 returned to normoxic levels, while CBF declined to a lower but still elevated level (+150%). CBF/CMRO2 increased twofold, while cerebral fractional extraction of O2 was unchanged. Mean arterial pressure was unchanged, but cerebral venous pressure rose (+11 mmHg) in a stable fashion such that cerebral perfusion pressure declined by 13%. Cerebral venous hematocrit and hemoglobin concentration were both elevated (+2.2-2.7% Hct units; +1.0-1.3 g/dl, respectively) above the corresponding arterial values between 150 and 210 min of hypoxia, suggesting venous hemoconcentration in possible association with a transcapillary fluid shift. CBF, and especially CVR, were well correlated with arterial O2 content.     

Fetal cardiovascular responses to asphyxia induced by decreased uterine perfusion

Cardio-respiratory responses to asphyxia produced by decreased uterine perfusion were studied in 15 sheep fetuses. In chronic (spinal-anesthetized) and acute (inhalation-anesthetized) preparations, we measured fetal PO2, PCO2, pH, heart rate, arterial and umbilical venous pressures at rest and 5 min after controlled reductions of maternal aortic blood flow. Umbilical blood flow was determined by electromagnetic flow transducer on the fetal descending aorta with the iliac arteries ligated, in conjunction with radionuclide-labelled microspheres. In contrast to previous studies in which fetal hypoxaemia was produced by decreased maternally inspired O2 concentrations, decreasing degrees of uterine perfusion were associated with increasing degrees of hypercapnea and acidemia, as well as hypoxaemia. In chronic experiments, heart rate and umbilical blood flow fell significantly in response to decreased uterine perfusion with all degrees of hypoxaemia studied. In acute experiments, during the control period, PO2 values were similar to those of chronic experiments while values for pH and umbilical blood flow were lower and those for umbilical vascular resistance were higher. In the acute experiments, hypoxic stresses identical to those in the chronic studies failed to produce significant hemodynamic changes, except for bradycardia in response to severe hypoxaemia. These differences were apparently due to the pharmacologic effects of halothane and the operative stresses.