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Biomedical subjects

R I Stark

Publications and source records attributed to R I Stark.

At least 73 records · Page 4Linked to original sources

Effect of hypoxemia and acidemia on the fetal cardiac response to acetylcholine: experimental observations in fetal baboons.

The effect of hypoxemia and acidemia on the fetal cardiac response to acetylcholine (ACh) was studied in 24 baboon fetuses in utero. A bolus injection of ACh was given intravenously to the fetus at a dose that ranged from 5 to 160 micrograms/kg of estimated fetal weight. The responses were divided into two groups according to fetal oxygenation and acid-base state. Fetuses in group I were well oxygenated (PaO2, 31 +/- 1.4 mm Hg; pHa, 7.32 +/- 0.154; only five atrioventricular (A-V) heart blocks were induced with 50 +/- 3.3 micrograms/kg of ACh. Fetuses in Group II were hypoxemic (PaO2, 18 +/- 1.2 mm Hg) and acidemic (pHa, 7.05 +/- 0.048); ten A-V heart blocks were induced with a comparable dose of ACH (45 +/- 6.8 micrograms/kg). Dose response relationship is noted in individual fetuses with multiple dosage injections. These findings suggest that the fetal cardiac response to ACh is both dose related and more profound when the fetus is hypoxemic and acidemic, and indicate that the hypoxic and acidotic fetus is at a greater risk from strong stimulation of the parasympathetic nervous system. Atropine prevented myocardial conduction defect induced by intravenous injection of ACh even in the severely hypoxemic baboon fetus. This observation suggests that judicious use of atropine could be a life-saving measure when a prolonged severe degree of cord occlusion is suspected.

Acetylcholine↗

Bradycardia in the fetal baboon following paracervical block anesthesia.

In order to define the causal relationship between the use of local anesthetics and fetal bradycardia, paracervical block anesthesia (PCB) with lidocaine of 2-chloroprocaine was induced on 52 occasions to 27 pregnant baboons. The dosages were comparable to those used clinically on the basis of maternal body weight. On 40 occasions, PCB was induced with nonasphyxiated (normal) fetuses, 33% of which developed fetal bradycardia after PCB. Fifty percent of these episodes of fetal bradycardia were accompanied by a decrease in PaO2. The other 12 fetuses had pHa less than 7.25, and SaO2 less than 25%, and all exhibited bradycardia with further decreases in pHa and PaO2. A transient increase in uterine activity with a significant reduction in uterine blood flow occurred in 73% of the mothers after PCB. Peak concentrations of lidocaine of 2.3 +/- 0.2 (SE) micrograms/ml in the maternal blood and 0.8 +/- 0.2 micrograms/ml in the fetal blood were found at 8 min after PCB. These levels were far below those associated with myocardial toxicity. The conclusion is that the fetal bradycardia subsequent to PCB is, in part, caused by a decrease in the oxygen available to the fetus secondary to an increase in uterine activity and a reduction in uteroplacental perfusion. This manifestation may occur at drug concentrations in both the mother and fetus that are far below toxic levels.

Anesthesia, Local↗

Toxicity of lidocaine in adult, newborn, and fetal sheep.

The relative central nervous system and cardiovascular toxicity of lidocaine was compared in adult, newborn, and fetal sheep during continuous infusion of lidocaine into the jugular vein at the rate of 2 mg x kg-1 x min-1. An identical sequence of toxic manifestations occurred in the adult, newborn, and fetus: convulsions, hypotension, respiratory arrest, and circulatory collapse. Doses necessary to produce these manifestations were highest in fetuses and lowest in adults. For example, in order to elicit convulsions, 5.8 +/- 1.8 mg/kg of lidocaine was required in the adults, 18.4 +/- 2.2 in the newborns, and 41.9 +/- 6.0 in the fetuses. Measurements of lidocaine concentrations in blood demonstrated that these toxic symptoms occurred at levels which were not significantly different among the three groups. The results indicate that fetal and newborn lambs are no more sensitive to lidocaine toxicity than are adult sheep. The fact that the highest doses were required in the fetuses is probably related to the placental clearance of the drug into mothers and better fetal maintenance of arterial Po2 despite convulsions and respiratory arrest (cessation of breathing-like movements).

Animals↗

Release of vasopressin by the fetal lamb during premature parturition induced with corticotropin.

These studies were implemented to assess the relationship between fetal vasopressin secretion and the progression of parturition as well as the contribution of specific stimuli to vasopressin release during labor. In chronically catheterized fetal lamb preparations, labor was induced by infusion of adrenocorticotropin (12.5 mg/kg/hr) to seven fetuses at 130 +/- 1 day of gestation. Before labor, fetal plasma vasopressin concentrations were 2.1 +/- 1.4 pg/ml and remained low (5.3 +/- 3.4 pg/ml) during prodromal and early phases of labor, but rose significantly in the active and expulsive phases (39.6 +/- 27.5 and 173.3 +/- 152.9 pg/ml) to reach peak values at delivery (584.2 +/- 433 pg/ml) and decrease by 30 min after birth (359.8 +/- 90.0 pg/ml). At delivery, fetal plasma vasopressin concentrations were strongly correlated (P less than 0.001) with hormone values obtained during the latter phases of labor. Fetal arterial pH and oxygen tension was inversely correlated with plasma vasopressin (P less than 0.01). No similar correlations were found with arterial PCO2, K, Na, Cl, osmolality, or packed cell volume. Unexpectedly, we observed a significant (P less than 0.001) and progressive decrease in fetal oxygen tension during the induction process. Other characteristics of adrenocorticotropin-induced parturition seemed to mimic those of spontaneous labor.

Adrenocorticotropic Hormone↗

Human plasma beta-endorphin during pregnancy, labor, and delivery.

beta-Endorphin immunoactivity was measured in the plasma of 50 pregnant women, 25 nonpregnant women, 19 women during labor, and 25 women at the time of vaginal delivery. Simultaneous maternal and umbilical cord plasma samples were obtained in 23 cases. Mean beta-endorphin immunoactivity in the pregnant women was 15.6 +/- 1.6 pg/ml. No significant differences in mean beta-endorphin concentration were found in the first, second, or third trimesters until after the onset of labor, and at no time during this interval did levels differ from the mean of 12 +/- 1.9 pg/ml found in nonpregnant controls. In early labor, beta-endorphin was not elevated (14.8 +/- 2.3 pg/ml), but rose in the later stages of labor (cervical dilatation, > 4 cm) to 70.3 +/- 8.2 pg/ml and peaked during delivery at 113 +/- 13.3 pg/ml. Chromatography of plasma from women at delivery, pregnant women not in labor, and nonpregnant controls to separate beta-endorphin from cross-reacting beta-lipotropin showed mean beta-endorphin to beta-lipotropin molar ratios of 0.22-0.27 in the three groups, with no significant differences among the groups. In 23 subjects in whom simultaneous maternal and umbilical cord plasma samples were obtained, there was no correlation between the beta-endorphin immunoactivity in the paired samples, supporting the concept that fetal beta-endorphin is not of maternal origin. In 13 fetal umbilical cord samples, ACTH was measured in addition to beta-endorphin immunoactivity. A close correlation (r = 0.836) was observed between the concentrations of the two peptides, suggesting that in the fetus, as in the adult, beta-endorphin and ACTH are processed in parallel from a common precursor.

Adolescent↗

Amniotic fluid fluorescence polarization value as a predictor of respiratory distress syndrome.

Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene in amniotic fluid lipid aggregates was measured to determine the ability of this technique to prospectively predict respiratory distress syndrome. Prior retrospective studies have shown that an FP value of less than or equal to 0.336 correlated best with a lecithin to sphingomyelin ratio of greater than 2.0. Fluorescence polarization values of amniotic fluid samples obtained within 48 hours of birth from 161 pregnancies were correlated with neonatal outcome. Samples from 149 pregnancies had FP values of less than or equal to 0.336 and samples from 12 pregnancies had FP values of greater than or equal to 0.336. No infants delivered from the former group developed RDS and eight of 12 infants from the latter group developed RDS (P less than 0.001). In the entire population the test had a sensitivity of 100% and a specificity of 97%. When 37 infants with birth weights less than 2,500 gm were studied, the FP value remained a highly reliable predictor of the infant at risk for developing RDS (P less than 0.001). In this subset the test had a sensitivity of 100% and a specificity of 90%. L-S ratios were performed on 96 samples and the results correlated well with FP values (P less than 0.001). We conclude that the amniotic fluid FP value is a reliable index of fetal lung maturity and the risk for developing RDS. The FP value also has specific technical and diagnostic advantages over the L-S ratio.

Amniotic Fluid↗

Relationship of fetal bradycardia to maternal administration of lidocaine in sheep.

The casual relationship between the use of lidocaine and fetal bradycardia and the effect of the drug on maternal and fetal hemodynamics were studied on 13 chronically instrumented pregnant sheep. Lidocaine was infused intravenously to the mother for 60 minutes during arterial lidocaine concentrations were maintained at 2 to 5 microgram per milliliter in the mother and at less than 2 microgram per milliliter in the fetus. A decrease in uterine blood flow and an increase in uterine vascular resistance and uterine activity occurred immediately following the administration of lidocaine to the ewe. These changes were followed by a transient fetal bradycardia in 12 out of 17 experiments, accompanied by a decrease in fetal PaO2 values. These phenomena were seen in the absence of such predisposing conditions as maternal hypotension and fetal acidosis. It would appear that the mechanism responsible for a transient fetal bradycardia following regional obstetric anesthesia, particularly paracervical block anesthesia, in the initially nonasphyxiated fetus may in part be related to a brief decrease in perfusion of intervillous spaces. The bradycardia can occur at low lidocaine concentrations in both the maternal and fetal blood in a range similar to that observed in clinical practice.

Anesthetics, Local↗

Arginine vasopressin during gestation and parturition in sheep fetus.

The possible correlation between plasma arginine vasopressin (AVP) concentration and the processes leading to parturition was assessed in 11 chronically catheterized pregnant ewes. Samples of blood withdrawn intermittently during a 20-day period preceding labor and during parturition were analyzed for AVP by a specific radioimmunoassay, as well as for pH, PaCO2 and PaO2. Fetal AVP was 1.74 +/- 1.55 pg/ml and maternal AVP 1.47 +/- 0.74 pg/ml (mean +/- SD). No preparturient rise in fetal vasopressin was noted, but levels increased progressively during labor to reach peak levels in cord blood (range 7.5--8,000 pg/ml). There was no consistent rise in maternal vasopressin during the same interval. A relationship between prolonged antepartum intrauterine asphyxia and increases in fetal vasopressin was noted. It is concluded that the markedly elevated levels of vasopressin observed in cord blood are the result of intrapartum 'stress', but are not related to the initiation of parturition.

Animals↗

Plasma beta-endorphin and beta-lipotropin in the human fetus at delivery: correlation with arterial pH and pO2.

Beta-endorphin-like immunoactivity was measured in the umbilical cord plasma of 45 term human fetuses. Mean concentration was 91 +/- 16 (SEM) pg/ml,an the normal adult level of 30.7 +/- 2.7 pg/ml. This immunoactivity was further characterized in 10 cases by Sephadex G-50 chromatography to separate beta-endorphin from beta-lipotropin (beta-LPH). Mean beta-endorphin and beta-LPH concentrations were 57 +/- 12.8 and 455 +/- 101 pg/ml, respectively. Both were higher (P less than 0.01) than the mean beta-endorphin and beta-LPH concentrations reported in the adult. The mean molar beta-endorphin to beta-LPH ratio was 0.35 in the fetus and 0.36 in the adult. In 17 fetuses whose umbilical arterial and venous concentrations were measured separately, mean beta-endorphin-like immunoactivity was higher in the artery than in the vein. A highly significant negative correlation (r = -0.831; P less than 0.001) was present between umbilical arteiral pH and beta-endorphin-like immunoactivity. A negative correlation (r = -0.611; P less than 0.005) with arterial pO2 was also noted. We conclude that high levels of beta-endorphin-like immunoactivity, composed of both beta-endorphin and beta-LPH, circulate in the human fetus at term, and that hypoxia and secondary acidosis may be major stimuli to the release of these peptides.

Adult↗

Amniotic fluid microviscosity determined by fluorescence polarization: methodology and relation to gestational age.

The fluorescence polarization of 116 amniotic fluid specimens obtained from 22 isoimmunized pregnant women was determined. The degree of fluorescence polarization of amniotic fluid provides an index of microvisocity in lipid aggregates that is dependent on the lecithin-to-sphingomyelin ratio and the degree of saturation of fatty acid side chains. We confirmed the reproducibility of the measurement of amniotic fluid microviscosity (coefficient of variation, 2.0%). The measurements are not effected by bilirubin concentration of amniotic fluid dilution. The pattern of change of amniotic fluid microviscosity during gestation parallels the expected development of the surfactant system. Amniotic fluid microviscosity is high during early gestation and abruptly and sequentially decreases between the 28th and 36th week of gestation. Since the measurements are an accurate reflection of the biochemical properties of amniotic fluid lipids and parallel the development of the surfactant system, we conclude that amniotic fluid microviscosity may well serve as an indicator of the process of fetal lung maturation.

Amniotic Fluid↗

Renal response of fetal lamb to complete occlusion of umbilical cord.

The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure.

Acid-Base Equilibrium↗

Determination of fetal lung maturity by fluorescence polarization of amniotic fluid.

The degree of fluorescence polarization (P value) of 1,6-diphenyl-1,3,5-hexatriene has been shown to be an excellent indicator of the lecithin/sphingomyelin (L/S) ratio in laboratory prepared liposomal dispersions. In order to test the validity of this technique in amniotic fluid, the L/S ratio and P value of 161 amniotic fluid specimens were determined. In 127 the P value was less than or equal to 0.336 and the L/S ratio was greater than or equal to 2. In 26 the P value was greater than 0.336 and the L/S ratio was less than 2 (P less than 0.05). The amniotic fluid P value is affected by blood or meconium but not by surgical lubricants or bilirubin. We concluded that the degree of fluorescence polarization of amniotic fluid indicates fetal lung maturity as reliably as the L/S ratio. However, this method has important technical and practical advantages that make it more applicable for a clinical laboratory.

Amniotic Fluid↗

Effects of terbutaline on the pregnant baboon and fetus.

The effects of terbutaline on the mother and fetus were evaluated in 8 near-term pregnant baboons. Significant suppression of postoperative spontaneous and oxytocin-augmented uterine activity was achieved with infusion rates of 0.36 and 0.56 microgram/kg/min, respectively. Maternal and fetal blood pressure and acid-base states as well as fetal heart rate were unaffected by the administration of terbutaline to the mother, but a mild maternal tachycardia was observed. Both maternal and fetal blood glucose increased during terbutaline infusion. Direct administration of terbutaline to the fetus did not alter the fetal cardiovascular or acid-base state. It is concluded that in the baboon, terbutaline is an effective tocolytic agent with minimal untoward effects on either mother or fetus.

Acid-Base Equilibrium↗

The effect of diazoxide on uterine blood flow in pregnant sheep.

Diazoxide, a labor inhibiting agent, was administered intravenously at various rates to seven pregnant, near-term sheep to evaluate its effect on cardiovascular and uterine hemodynamics. Uterine blood flow was measured with electromagnetic flow transducers. Rapid administration of diazoxide resulted in a profound maternal tachycardia with hypotension, an increase in uterine vascular resistance, and a significant decrease in uterine blood flow. With slow infusion of the drug, the changes in heart rate and blood pressure were minimized, uterine vascular resistance was decreased, and uterine blood flow was maintained. Therefore, slow infusion appears to be the preferred method for inhibiting labor with diazoxide.

Animals↗