Lactate in fetal tissue during hypoxia; correlation to lactate, pH and base deficit in the fetal blood.

It was the aim of this study to investigate the relationship between the tissue concentrations of lactate in different organs, the blood lactate concentrations, and pH and base deficit in the extracellular fluid (BDecf) during fetal hypoxia. With regard to fetal blood analysis during labour the question is of major importance to what extent blood measurements can provide information concerning intracellular lactate concentrations, especially in the cerebral tissue. In 15 guinea-pig fetuses acute hypoxia was induced by anaesthesia, operative stress and abruption of the placenta. After puncture of the umbilical artery for blood analysis, tissue specimens were taken from the cerebral tissue, heart, liver, lung, muscle and fascia of the abdominal wall, bowel and kidney within 1 to 2 minutes and analyzed for lactate. The lactate concentrations were corrected according to the time interval from blood sampling to collection of tissue specimen. In acute hypoxia the lactate concentrations of the heart and the cerebral tissue were closely correlated to lactate, pH and base deficit measured in arterial blood. The tissue concentration of lactate in the heart and in the cerebrum exceeded the blood level approximately by 70 and 30-50%, respectively. At a pH greater than 7.10 and BDecf less than 8 mumol/ml, the lactate concentration in the cerebrum was about half the lactate concentrations leading to cerebral edema and cell necrosis in the hypoxic monkey fetus (Myers RE. In: Gluck L, ed. Intra-uterine asphyxia and the developing fetal brain. 1977, 37-97).

Plasma free and sulfoconjugated catecholamines during acute asphyxia in the sheep fetus--relation to cardiovascular parameters.

Changes of free and sulfoconjugated catecholamines were measured radioenzymatically during a 5 minute period of acute asphyxia in chronically instrumented sheep fetuses (n = 5). Due to total reduction of uterine blood flow asphyxia as well as metabolic acidosis developed (pH = 6.94 +/- 0.02; Pco2 = 98 +/- 8 mmHG; lactate = 7.1 +/- 0.3 mmol/l). Peak concentrations of free catecholamines were reached after 3 minutes; free NE increased 60-fold, free E 370-fold and free DA 13-fold as compared to control values. Concomitantly, sulfoconjugated catecholamines rose markedly and were 40-fold (NE), 300-fold (E) and 10-fold (DA) higher when compared to the control period. Thus, the results reveal that the fetal sulfoconjugating system is very effective and able to match high concentrations of free catecholamines entering the circulation. After release of occlusion, free and sulfoconjugated catecholamines decreased with a half life time of 2.5 to 4.3 minutes during the initial 10 minutes. A close correlation could be demonstrated between free catecholamines and fetal arterial blood pressure, however, with interference of the effects of desoxygenation on the myocard. Moreover, fetal tachycardia is related to circulating catecholamines, especially E, during the postasphyxial period. Our results suggest, that in unstressed, normoxic fetuses the cardiovascular system is able to maintain basic functions (heart rate and blood pressure) during asphyxia for 5 minutes. In this context, a maximal sympathoadrenal stimulation with secretion of free catecholamines seems to be essential.

Fetal sympathetic activity, transcutaneous PO2, and skin blood flow during repeated asphyxia in sheep.

To improve detection of fetal distress, we examined whether increased fetal sympathetic activity during repeated episodes of asphyxia decreases skin blood flow, which can be monitored by recording transcutaneous PO2. Sympathetic activity was assessed by relating catecholamine concentrations in the fetal plasma to blood gas, acid-base, and heart rate variables which are commonly used to determine fetal distress. Fifteen experiments were conducted on 8 anaesthetised fetal sheep in utero between 125 and 145 days of gestation (term is at 147 days). They were subjected to 11 consecutive episodes of asphyxia of 30 (n = 3), 60 (n = 9), or 90 (n = 3) s over 33 min, achieved by arrest of uterine blood flow. Blood samples were drawn at 0, 33, and 60 min to determine arterial blood gases, acid base-balance, and concentrations of lactate, glucose, norepinephrine, and epinephrine. Fetal transcutaneous PO2, relative local skin blood flow, heart rate, arterial blood pressure, and arterial O2 saturation were recorded continuously. Fetal plasma concentrations of norepinephrine and epinephrine increased logarithmically as the duration of repeated asphyxia, anaerobic metabolism, and glucose concentrations increased, and as the mean O2 saturation, transcutaneous PO2, and local skin blood flow decreased. We conclude that during repeated episodes of asphyxia in fetal sheep near term, a significant increase in sympathetic activity can be detected indirectly by transcutaneous PO2 monitoring, because sympathetic activation reduces skin blood flow.

[Metabolic, cardiovascular and sympathoadrenal reactions of the fetus to progressive hypoxia--animal experiment studies]. / Metabolische, kardiovaskuläre und sympathoadrenale Reaktionen des Feten auf eine progrediente Hypoxie--Tierexperimentelle Untersuchungen.

During delivery a reduction of placental blood flow in relation to uterine contractions resulting in repetitive decelerations of the fetal heart rate is frequently encountered. In this context the question arises whether a critical threshold of oxygen saturation (SO2) in fetal arterial blood can be defined, below which a severe fetal acidosis and a fetal shock syndrome may develope. In chronically instrumented ewes (8 experiments) a slowly progressive fetal hypoxia was induced by stepwise reduction of uterine blood flow via occlusion of the maternal aorta. Fetal arterial blood pressure and heart rate were continuously monitored and fetal arterial blood samples were taken intermittently from a catheter placed in the fetal aorta. The stepwise decrease of fetal arterial SO2 was 10% at time intervals of 15-30 minutes. With SO2-values above 15%, lactate increased 0.01-0.03 mmol/l/min and the pH decreased 0.003-0.0012/min. A significant increase of lactate concentration (0.1-0.3 mmol/l/min) and decrease of the pH (0.003-0.009/min) was encountered when the fetal arterial SO2 was below 15%. With progressive desoxygenation systolic and diastolic blood pressure as well as pulse pressure increased. There was no uniform reaction pattern of the basal fetal heart rate to progressive hypoxia; while in some experiments tachycardia prevailed, bradycardia was encountered in other experiments. Plasma free catecholamines exhibited an inverse relationship to SO2 with an exponential increase of catecholamine concentrations when SO2 fell below 15-20%. During almost complete desoxygenation (SO2 below 5%), catecholamine concentrations were increased 100 fold (norepinephrine), 1000 fold (epinephrine) and 50 fold (dopamine) as compared to control values. In comparison to free catecholamines increases of the concentrations of cortisol and aldosterone were only small. The increase of cortisol with progressive hypoxia may explain the endogenous stimulation of lung maturity during fetal stress. Our experiments suggest that a SO2 level of 15-20% represents a critical threshold for development of severe fetal acidosis and a fetal shock syndrome. However, even during severe hypoxia (SO2 below 10%) the sheep fetus is able to maintain blood pressure for at least 30 minutes with the help of an excessive catecholamine secretion. Only with anoxia a breakdown of fetal circulation has to be anticipated within a few minutes.

[Effect of infusion acidosis on the condition of the fetus--animal experiment studies]. / Einfluss der Infusionsazidose auf den Zustand des Feten--tierexperimentelle Untersuchungen.

In order to assess the effect of acid infusion on fetal cardiovascular functions, oxygenation, glucose and electrolyte concentrations, 8 experiments were performed on chronically instrumented ewes. A severe metabolic acidosis (pH less than 7.10, BDECF = 13.5 mmol/l) was induced by intravenous infusion of L(+) lactate into the fetus. There was no significant alteration of baseline fetal heart rate and oscillation amplitude. The blood pressure exhibited a slight increase, probably due to the administration of volume (87-204 ml in 90-210 min). PO2 remained constant while SO2 showed a decrease in the order of 10%, due to the change in oxygen affinity of the fetal blood produced by the Bohr effect. Levels of glucose increased significantly, whereas electrolyte concentrations remained unchanged. After the end of infusion, pH-values returned to the normal range within 110 min. Lactate and BDECF decreased with a half life time of 95 and 48 min, respectively (mean SO2 = 28%). We conclude that a severe metabolic acidosis in the extracellular space does not affect the normal fetal heart rate pattern (baseline, oscillation amplitude) and has no acute deleterious effects on the fetus. Hence, when the actual fetal pH during labor is found to be low, a maternogenic infusion acidosis should be excluded by a simultaneous feto-maternal blood gas analysis.

[Fetomaternal blood analysis in the diagnosis of subpartal hypoxia of the fetus]. / Die fetomaternale Blutanalyse (FMBA) zur Diagnose der Hypoxie des Feten sub partu.

UNLABELLED: Clinical and animal experiments suggest that fetal metabolic acidosis is influenced by placental transfer of lactate and bicarbonate. It was the aim of this study to answer the following questions: What kind of relationship does exist between fetal metabolic acidosis and maternal metabolic acidosis? Does fetal metabolic acidosis coincide with alterations of fetal heart rate and fetal oxygenation? Does the maternofetal difference of base deficit reflect fetal oxygen deprivation more accurately than the measurement of fetal base deficit alone? What is the maternofetal difference of base deficit in normoxia and mild hypoxia? In 100 pregnant women (gestational age greater than 37 weeks, fetal weight greater than 3 rd percentile) a fetomaternal blood analysis (FMBA) was performed during labour and immediately after delivery. The metabolic acidosis was measured as base deficit of extracellular fluid (BDECF). RESULTS: The fetal metabolic acidosis depends mainly on the buffer base concentration in the maternal blood. Moderate repetitive hypoxemia with no severe pathological FHR-alterations do not show a significant relationship to fetal metabolic acidosis. Moderate hypoxia (defined as the combination of oxygen saturation below 30%, periodical decelerations and basal fetal heart rate above 160 b/min) can be recognized most accurately by determining the maternofetal differences of BDECF. In fetal normoxia BDECF in the maternal blood is 4 mmol/l higher than in the fetal blood, in moderate hypoxia the maternofetal difference of BDECF is reduced to 1 mmol/l. These findings are in accordance with the results of Roversi et al. (1975). Conclusions for the intensive surveillance of the fetus during labour by fetal blood analysis: Within the range of pH 7.10-7.30 the maternal BDECF should be determined in addition to the fetal BDECF to calculate the maternal fetal difference of BDECF. If BDECF in the fetus exceeds the maternal BDECF, the risk of fetal hypoxia is increasing. In these cases, delivery should be performed as soon as possible avoiding additional hypoxic or mechanical birth injuries. The technical procedure of fetal maternal blood analysis is described and the difficulties of routine use are discussed.

Repetitive reduction of uterine blood flow and its influence on fetal transcutaneous PO2 and cardiovascular variables.

The influence of repeated asphyxia on fetal transcutaneous PO2, relative local skin perfusion, heart rate, blood gases and pH was investigated in 15 experiments on 8 acutely instrumented sheep fetuses in utero between 125 and 145 days gestation (term is 147 days). Uterine blood flow was intermittently arrested (11 times within 33 min) by intra-vascular maternal aortic occlusion, exposing the fetuses to repeated episodes of asphyxia of 30 (n = 3), 60 (n = 9) and 90 (n = 3) s duration. The fetal transcutaneous PO2 fell as the duration of asphyxia (2 alpha less than 0.01), heart rate deceleration area (2 alpha less than 0.01) and acidaemia (2 alpha less than 0.01) increased. With decreasing skin perfusion, which was dependent on the duration of asphyxia (2 alpha less than 0.001) and acidaemia (2 alpha less than 0.001), a discrepancy developed between transcutaneous and arterial PO2. The increase (delta) in transcutaneous-arterial PO2 difference was related linearly to the duration of asphyxia (2 alpha less than 0.01), the mean haemoglobin oxygen saturation (2 alpha less than 0.001), acidaemia (2 alpha less than 0.001) and relative local skin flow (2 alpha less than 0.05). It was highest after severe episodes of asphyxia (90 s), when O2 saturation, skin blood flow and arterial blood pH values were low. Fetal heart rate deceleration area was only correlated with the cutaneous-arterial PO2 difference when the mean fetal haemoglobin oxygen saturation was below 35%. Thus, a discrimination of heart rate decelerations that are significant for the fetus seems to be possible, when associated with low transcutaneous PO2 values. We conclude that in the sheep fetus transcutaneous PO2 measurements during repeated asphyxial episodes yield information on fetal oxygenation and on the skin vasomotor response.

[Effect of the beta-blocker metoprolol on the cardiovascular system and plasma catecholamines of the fetus in normoxia and acute hypoxia--animal experiment studies]. / Einfluss des Beta 1-Blockers Metoprolol auf das kardiovaskuläre System und die Plasmakatecholamine des Feten bei Normoxie und akuter Hypoxie--tierexperimentelle Untersuchungen.

Metoprolol, a beta 1 blocking agent, is being used with increasing frequency during pregnancy for treatment of disorders such as hypertension or beta-mimetic induced tachycardia. Since it is well documented that beta-blocking agents are able to cross the placenta, the question arises whether these drugs have any adverse effect on the fetal metabolic or cardiovascular system. It was the aim of this animal experimental study to investigate the following questions: 1. Does metoprolol exert a negative influence on fetal metabolic and cardiovascular functions during normoxia? 2. Is the fetal reaction to an acute short period of hypoxemia altered by metoprolol? To answer these questions, experiments were carried out in 6 pregnant sheep at 110-130 days of gestation. In 8 experiments metoprolol was infused into a fetal vein in increasing dosage (0,04-0,32 mg/min). In a second series of experiments (n = 8), an acute hypoxemia was induced by complete reduction of uterine blood flow for 1 minute, and the results obtained with or without metoprolol were compared. Metoprolol does not exert a negative influence on fetal oxygenation, acid-base balance, lactate concentration and blood pressure, although the metoprolol concentration measured in fetal plasma was relatively high (two - to threefold above therapeutic metoprolol levels). Thus, definitive adverse effects on the fetus induced by metoprolol are not recognizable. The fetal sympathoadrenal reaction to an acute hypoxemia, as measured by the concentration of the free catecholamines epinephrine, norepinephrine and dopamine in the fetal plasma, is also unchanged by metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Catecholamines in arterial and venous umbilical blood: placental extraction, correlation with fetal hypoxia, and transcutaneous partial oxygen tension.

In 34 parturient women the levels of free epinephrine (E), norepinephrine (NE), and dopamine (D) were determined by a radioenzymatic method using maternal venous and umbilical arterial and venous blood. The study was conducted to investigate the relationship between fetal catecholamines and hypoxia, fetal heart rate (FHR), and transcutaneous pO2 (tcpO2). The placental catecholamine extraction rates were also calculated. Results The NE concentrations (10,200 pg/ml) and the E concentrations (1,120 pg/ml) in the fetal arterial blood were highly elevated with mean values increased 4-fold over umbilical vein values. Compared with the maternal venous blood, NE values were increased 20-fold, and E values 10-fold. Free D concentrations in fetal arterial blood (130 pg/ml) had risen 2.5-fold over maternal levels. These results suggest that the catecholamines measured in cord blood are of fetal origin and that the placenta has a high capacity for inactivation of free catecholamines. The placental extraction rate is 77 +/- 14% for NE, 76 +/- 16% for E, and 33 +/- 25% for D. The placental extraction rates for E and NE were virtually identical; in agreement with morphological studies they demonstrated absence of sympathetic innervation on the fetal side of the placenta. Highly significant correlations were found between fetal arterial NE concentrations and the 1-minute APGAR score, pH and base deficit in the umbilical artery and alterations of the FHR (deceleration area, baseline FHR). Further analysis of FHR alterations reveals that an increase in deceleration area without tachycardia is not correlated with an increase of fetal arterial NE concentration. A significant rise in NE was only found with additional tachycardia which is often associated with a loss of oscillation amplitude. Fetal arterial E concentrations were found to correlate with the fetal parameters indicating increased adrenal secretion of the hormone during fetal stress. However, correlation coefficients were lower than those obtained for NE. A significant effect of fetal hypoxia on arterial and venous D levels could not be demonstrated. Fetal tcpO2 varies between 0-25 mm Hg during the last two hours before delivery. In most cases tcpO2 was lower than the arterial pO2. Besides epidermal thickness and artifacts, skin perfusion is a major factor influencing the tcpO2 (transcutaneous arterial pO2 difference). Vasoconstriction of the cutaneous vessels induced by increased NE secretion during hypoxia may obviously produce a fall in tcpO2.(ABSTRACT TRUNCATED AT 400 WORDS)

[Method of delivery of premature infants--abdominal or vaginal?]. / Zum Geburtsmodus bei Frühgeborenen--abdominal oder vaginal?

In regard to the present perinatal mortality for prematures with cephalic presentation, a general cesarian section below certain limits in weight and gestation cannot be recommended. The management of prematurity must be individualized and depends on additional risk factors. In case of doubt, the abdominal delivery is to prefer especially in a patient with less than 32 weeks of gestation or an estimated fetal weight of 1500 g or less. At least a potential risk for the fetus by anaesthesia and surgery has also to be considered. Vaginal delivery is justifiable especially in patients with unruptured membranes, high pelvic score and expected rapid delivery and with no additional fetal or maternal risk factors. Special attention must be paid to a gentle delivery of the head. These statements are based on present data of fetal mortality and probably of the same significance for fetal morbidity, especially the development of intraventricular hemorrhage.

[Intraperitoneal adhesion formation and tissue reaction following the use of microsurgical suture material]. / Intraperitoneale Adhäsionsbildung und Gewebereaktion bei mikrochirurgischem Nahtmaterial.

In 60 female rats we investigated intraperitoneal adhesion and tissue reaction of Vicryl, PDS, Ethilon und Prolene depending on the thickness of the thread (6-0 versus 9-0) and the length of the ends of the threads cut off in the region of the knot. The results did not show any significant difference in respect of degree of adhesion and tissue reaction, for the four suturing materials tested in this study. It was also not possible to detect any definite influence of the thread strength (6-0 versus 9-0) on the adhesion and tissue reaction. Only in the case of Ethilon the intraperitoneal adhesion was significantly lower if the thread strength was 9-0, compared against 6-0 (p less than 0.02). With all the other types of thread, adhesion was found to be independent of the strength of the thread. However, the length of the ends of the thread in the region of the knot exercises a great influence on the degree of adhesion. If the ends of the threads have a length of 0.3 cm, adhesion is statistically significantly greater than if the ends have been cut short (p less than 0.001). Results from these animal experiments indicate that the choice of microsurgical suturing material does not depend on the type of thread, as far as intraperitoneal adhesion and inflammatory tissue reaction are concerned, whereas the thread strength (6-0 or 9-0) has a slight influence only. For preventing adhesion, it is important to cut off the ends of the threads as short as possible after knotting, i.e. as short as safety of the knot would permit.

Heart rate and blood pressure response and metabolic changes in the sheep fetus following reduction of uterine blood flow.

The cardiovascular and metabolic responses during acute fetal hypoxia were studied in 7 pregnant sheep near term. Complete reduction of uterine flow (UBF) for 180 s was performed in 13 experiments by inflating a balloon positioned in the maternal aorta. Fetal heart rate (FHR), systolic and diastolic blood pressure (BP) and fetal arterial oxygen saturation (SO2) were measured continuously. Blood samples were taken at short intervals and analyzed for pH, PCO2, PO2, SO2, base excess and lactate. Following the reduction of UBF, FHR began to rise after 4.7 +/- 14.4 (SD)s and fell after 31.3 s paralleled by the rise of the BP after 23.2 +/- 8.2 (SD)s. The fall of FHR was not related to the SO2 at control, but to the decline of the SO2 by 10-15%. There was no critical limit of SO2 at which the FHR started to fall and the BP began to rise. The rise of the FHR after UBF had been released was significantly correlated to the rise of SO2. Lactate production during hypoxia was related to the slope of the SO2 decline, i.e., to the fetal O2 consumption. The total metabolic response during hypoxia and recovery given by the pH area was correlated to the SO2 at control. No correlation between dip area of FHR and PH area could be established.

Transcutaneous PO2 and cardiovascular observations in the sheep fetus following the reduction of uterine blood flow.

On 11 near term pregnant sheep the response of the fetal transcutaneous oxygen partial pressure (tcPO2) was compared with the alteration of the oxygen saturation (SO2) and the PO2 in the fetal aorta (FA), fetal heart rate (FHR) and fetal arterial blood pressure (FA BP) following the reduction of uterine blood flow (UBF). The FA SO2 changed 12.3 (SD 3.1) sec and the tcPO2 26.6 (SD 7.9) sec after UBF was reduced. The tcPO2 response was also delayed after UBF was restored: 72.6 (SD 41.9) sec compared to the SO2 response: 23.9 (SD 14.4) sec. The reduction of UBF was paralleled by a rise of the FA BF and a fall of FHR. They were at control within 10 min after the reduction of UBF was released reflecting the normalization of the tcPO2. There was a tcPO2-FA PO2-difference which was due to the difference that exist between the carotid artery PO2 and the PO2 in the fetal aorta. The delayed response of the tcPO2 electrode was due to the response time of the electrode itself. The delay during the recovery period however was predominantly due to the peripheral vasoconstriction as proved by Norepinephrine injection. The tcPO2 reflects very close the fall of the FA BP and the rise of the FHR during the recovery period and vice versa. The importance of the tcPO2-PO2,a difference for the fetal condition during labor has still to be worked out.