Occupational vibration during pregnancy.
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Environmental Exposure↗
Biomedical subjects
R M Abrams
Publications and source records attributed to R M Abrams.
Inhalational administration of cocaine in sheep.
A pipe for administration of inhaled cocaine and its pyrolytic products in laboratory animals was developed and tested. In-vitro trials showed 30.0 +/- 5.2% (mean +/- SE) recovery of cocaine in solvent. Five non-pregnant ewes were instrumented with tracheal T-tubes and vascular catheters. After surgical recovery, ewes received three doses of cocaine (free base) in a randomized fashion; 2 mg/kg and 4 mg/kg both by inhalation, and 2 mg/kg intravenously. Arterial blood samples were collected and assayed for cocaine and its major metabolites by high performance liquid chromatography. Blood pressure and heart rate were continuously recorded. Cocaine administered by inhalation was eliminated with a half-life of 1.6 +/- 0.5 min (mean +/- SE) compared to 3.4 +/- 0.9 following intravenous administration (p less than 0.03). Likewise, clearance values were greater following inhalation, 5532 +/- 1756 ml/min/kg, than following intravenous administration, 163 +/- 20.6 ml/min/kg (p less than 0.04). Both routes of administration led to significant elevations in blood pressure, 7.5% increase after smoking vs 20% increase after intravenous administration. No correlation was found between inhalational dose of cocaine and peak plasma cocaine concentration.
Administration, Inhalation↗
Behavioral state transition and local cerebral blood flow in fetal sheep.
Local cerebral blood flow in four near term fetal sheep was evaluated continuously before and after natural alternations in fetal behavioral state. Measurements were made in fetuses several days following an aseptic surgery to place electrodes for behavioral state recordings as well as heated and reference thermojunctions in cortical and subcortical tissue. These thermojunctions were used to qualitatively assess local cerebral blood flow. The time of transition between rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) was based on visual inspection of strip chart recordings of electrocortical, electroocular, and neck electromyographic activity and application of published criteria for their assessment. To confirm that transition had occurred, the amplitude of the spectrum of the electrocorticogram in one-third octave bands centered around 1 Hz and 20 Hz was measured before and after the transition point. Mean cerebral blood flow rose significantly by 24 s (P less than 0.05) after the transition from NREMS to REMS and fell by 12 s after the transition from REMS to NREMS (P less than 0.05).
Animals↗
Disposition of cocaine in pregnant sheep. I. Pharmacokinetics.
Cocaine abuse by pregnant women is increasingly recognized as causing serious health consequences for mother and newborn. To assess the placental transfer and fetal effects of cocaine, we studied its pharmacokinetics following intravenous administration to the pregnant ewe and fetus. Following bolus doses of 0.5-4.0 mg/kg to ewes, cocaine appeared within 30 s in fetal circulation, with peak concentrations occurring in 4-5 min. The disappearance of cocaine in the fetal plasma paralleled that in maternal plasma, suggesting that a rapid equilibrium of cocaine occurred between maternal and fetal compartments. The mean half-life of cocaine in the fetus across doses (4.4-5.0 min) was similar to that in the ewe (4.0-5.6 min). Plasma clearance of cocaine in the ewe did not appear to vary according to dose. The fetal exposure to cocaine, as indicated by the area under the fetal plasma concentration versus curve, was a linear function of maternal cocaine dose (r = 0.96, p less than 0.01). These results demonstrate rapid placental transfer of cocaine after maternal administration in an animal model and rapid metabolism by mother and fetus.
Animals↗
Disposition of cocaine in pregnant sheep. II. Physiological responses.
We studied maternal and fetal blood pressure, heart rate, arterial blood gases and fetal behavioral state alterations in response to maternally administered cocaine hydrochloride in 11 pregnant sheep. Cocaine administration to the ewe caused a dose-dependent increase in maternal blood pressure and heart rate and in fetal blood pressure, and a decrease in fetal arterial oxygen tension. In the ewe, blood pressure changes corresponded linearly to dose administered (r = 0.88, p less than 0.001). Blood pressure changes were correlated to peak plasma cocaine concentration in the ewe (r = 0.52, p less than 0.01) and in the fetus (r = 0.43, p = 0.05). In addition, in 7 of 8 fetuses which had entered rapid eye movement (REM) sleep within 5 min of maternal cocaine administration, REM sleep was abruptly terminated either by the cocaine, fetal hypoxia or some other nonspecific event caused by the maternal cocaine administration. Maternal cocaine administration causes maternal and fetal hemodynamic alterations that have potential adverse effects in pregnancy.
Animals↗
Cocaine alters behavioral states in fetal sheep.
Intrauterine cocaine exposure causes subtle neurologic abnormalities in human newborn infants; however, the mechanism for these abnormalities is not known. To investigate whether cocaine alters fetal behavioral state, the electrocortical, electro-ocular and neck muscle electrical activity was monitored in 7 chronically instrumented fetal sheep before and during both saline and cocaine HCl infusions directly to the fetus. Saline infusion to the fetus had no effect on the percentage of time spent in rapid eye movement sleep compared to no infusion (37.5 +/- 11.6% vs 46.3 +/- 4.6%, mean +/- SD, P greater than 0.1). Cocaine infusion directly to the fetus had no effect on fetal arterial pO2, but did increase mean arterial pressure from 53.6 +/- 15 mmHg to 61.0 +/- 21 mmHg (P less than 0.01). In addition, during cocaine infusion, the percentage of time spent in rapid eye movement sleep dropped to 3.9 +/- 5.1% (P less than 0.0001) and the average duration of rapid eye movement epochs decreased from 10.1 +/- 3.0 min precocaine infusion to 1.9 +/- 2.6 min during cocaine infusion (P less than 0.02). The influence of cocaine was noted in a frequency analysis of the electrocorticogram. The amplitude of the energy centered at 1 Hz during cocaine infusion (73.8 +/- 4.0 dB) was greater than the amplitude during rapid eye movement sleep (65.5 +/- 4.7 dB) and less than the amplitude during non-rapid eye movement periods (79.9 +/- 4.5 dB) (P = 0.01). Cocaine appears to alter fetal behavioral state directly and this may play a role in the abnormal behavior in newborn infants exposed to cocaine in utero.
Animals↗
Local cerebral glucose utilization in normoxemic and hypoxemic newborn lambs.
To determine if hypoxemia altered local cerebral glucose utilization (LCGU) in newborn lambs, and where these alterations occurred, we measured LCGU using the 2-[14C]deoxyglucose [( 14C]DG) autoradiographic technique in lambs made hypoxemic by gradual reduction in inspired oxygen concentration. In 5 normoxemic control lambs, aged 3 days. LCGU of the cerebral cortex and white matter was higher than published values of LCGU in similar structures in near term normal fetuses and 2-4 times higher than reported values in normoxemic puppies. LCGU was highest in vestibular nuclei and auditory structures, followed by cerebellar nuclei, cerebral subcortical structures, and white matter. In 6 hypoxemic newborn lambs (paO2 14-18 torr) consistent increases in LCGU were noted only in the corona radiata compared to the values obtained in the normoxemic control lambs (36.5 +/- 8.1 vs. 23.9 +/- 1.7 mumol/100 per min, mean +/- S.D., P less than 0.02). This increase in LCGU in white matter was clearly noted in autoradiographs in which thin dark central regions within white matter often reached high into the gyri. In the hypoxic group. LCGU of the corona radiata superseded the value in many gray matter structures. In addition, patchy increases of [14C]DG utilization were present in the cerebral cortex of two hypoxemic lambs. Acute hypoxemia increases glucose utilization of the corona radiata to values equivalent to many gray matter structures, and leads to heterogeneous glucose metabolism in the cerebral cortex, but does not alter LCGU in other gray matter structures of newborn sheep.
Animals↗
Local cerebral blood flow is increased in rapid-eye-movement sleep in fetal sheep.
Behavioral state-induced changes in fetal cerebral blood flow were continuously monitored with a simple thermal dilution method. Thermojunctions were heated 1.5 degrees C above reference thermojunctions implanted contralaterally in various cerebral cortical and subcortical structures of four near-term fetal sheep. Temperature difference in rapid-eye-movement sleep was lower than in non-rapid-eye-movement sleep (p = 0.014), reflecting convective heat loss from increased blood flow. Temperature difference also varied significantly with the locus of placement in the brain (p = 0.003), reflecting, in part, regional differences in cerebral blood flow. The thermocouple method gives qualitative, continuous information on local cerebral blood flow that could be useful in monitoring the vascular response to changing functional activity during prenatal brain development.
Animals↗
Sound environment of the fetal sheep.
The internal sound pressure levels within the intact amnion of pregnant ewes surgically implanted with a hydrophone was determined during conditions of quiet and during sound field exposures to broadband and octave-band noise. Measurements were made of sound pressures outside and inside the ewe, and sound attenuation through maternal tissues and fluids was calculated. Sound pressures generated by low frequencies (less than 0.25 kHz) were 2 to 5 dB greater inside than outside the ewe. Above 0.25 kHz, sound attenuation increased at a rate of 6 dB per octave. For 4.0 kHz, sound attenuation averaged 20 dB. The sound pressure recorded at different locations within the amnion with respect to the sound source varied by up to 6 dB. The internal noise floor in the absence of externally generated sounds was as low as 50 dB (spectrum level) above 0.2 kHz. Thus the fetus is developing in an environment that is rich with internal and external sounds.
Acoustic Stimulation↗
Effect of high-intensity sound on local cerebral glucose utilization in fetal sheep.
The effects of external noise on fetal sheep cerebral glucose utilization were determined with the [14C]deoxyglucose method. Seventeen animals were prepared at 130 days gestation with catheters and electrodes for assessing fetal behavioral state. Five to 7 days later, 7 animals were studied under normal laboratory sound conditions (65-70 dB), 5 animals were exposed to 105-120 dB broadband noise levels produced by two earphones applied to the abdomen of the ewe, and 5 fetuses were stimulated with an electronic artificial larynx (EAL), positioned on the abdomen directly over the fetal head. There were no significant differences between local cerebral glucose utilization in controls and earphone ewes, and no obvious alteration in behavioral states. However, there were marked, significant differences in glucose utilization along the central auditory pathway during EAL stimulation. These autoradiographs revealed isofrequency-like bands in medial geniculate body and irregular darkening of cortex of the temporal lobe. Total time spent in clearly defined high and low voltage electrocortical activity did not change during EAL stimulation.
Animals↗
Effects of sound on fetal cerebral glucose utilization.
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Acoustic Stimulation↗
Local cerebral glucose utilization non-selectively elevated in rapid eye movement sleep of the fetus.
The [14C]deoxyglucose method for measuring local cerebral glucose utilization was employed in an effort to identify regions of the brain which participate in the increased neuronal activity of rapid eye movement (REM) sleep. The study was conducted in near term fetal sheep in which REM periods are of sufficient duration to obtain reliable data with this method. Neither the postulated executive centers of REM sleep nor those structures in the brainstem known to participate in the electrical activity peculiar to this sleep phase were found to have selectively elevated rates of glucose utilization. Rather, these regions shared equally with virtually all other structures in having rates higher than those which accompany non-REM sleep.
Animals↗
Intrauterine noise levels produced in pregnant ewes by sound applied to the abdomen.
Sound pressure in amniotic fluid was created by application of either an electronic artificial larynx or a standard audiometric earphone to the abdominal surface of pregnant ewes. Sound transmission was assessed with a hydrophone placed near the ear of the fetus within the intact amnion. Sound pressures produced by the electronic artificial larynx located directly over the hydrophone averaged 134.9 dB, whereas the highest sound pressure produced by a similarly placed earphone was 95.2 dB. Sound transmission decreased dramatically with increasing distance between the sound source and the hydrophone; this may account for some of the variability in fetal response when the sound test is used clinically. Caution is recommended in administering the sound test until the effects of high noise levels on the fetus are better understood.
Abdomen↗
Carboxy- and oxyhemoglobin in pregnant ewe and fetus after inhalation of marijuana, marijuana placebo and tobacco cigarette smoke.
We measured carboxyhemoglobin (HbCO) and oxyhemoglobin (HbO2) percent saturations and blood gases in four near-term pregnant ewes and their fetuses, during and for 6 hours after 9-12 minutes of smoke inhalation from one high-potency marijuana cigarette (M), a marijuana placebo cigarette (P), and a reference tobacco cigarette (T). Maternal HbCO reached maximum levels at or soon after the exposure (M, 2.8%; P, 3.5%; T, 6.3% above baseline) and fell to baseline values by 6 hours. Fetal HbCO rose slowly reaching a plateau at 3 hours (M, 0.7%; P, 1.1%; T, 2.0% above baseline) which was maintained for at least three additional hours. Reductions in maternal and fetal HbO2 after exposure to marijuana placebo and reference tobacco cigarettes reflected these rises in HbCO. After exposure to marijuana cigarettes, however, fetal HbO2 dropped precipitously by 17% of baseline and showed a prolonged rate of return to presmoking HbO2 levels. Although P exposure caused a greater change in HbCO in the fetus than did M, it had a less-profound effect on fetal oxygenation.
Animals↗
Effect of ketamine on local cerebral glucose utilization in fetal sheep.
Ketamine hydrochloride was infused intravenously in eight near-term fetal sheep, in doses ranging from 4.6 to 62.2 mg/kg. Local cerebral glucose utilization was determined by the [14C]deoxyglucose method. Heterogeneity in density of autoradiographs, a prominent feature in untreated fetal brains, was greatly diminished in animals receiving greater than 18 mg/kg, with differences between cerebral cortical gray and white matter virtually disappearing at high doses. In striking contrast to the pale, washed-out appearance in autoradiographs of most cerebral, cerebellar, and brain stem structures was a relatively high density of entorhinal cortex, hippocampus, lateral olfactory tract, and olfactory bulbs. Local cerebral glucose utilization of most gray and white matter structures was elevated in one ketamine-treated fetus experiencing a marked drop in PO2 during the study.
Animals↗
Local cerebral glucose utilization in fetal sheep exposed to noise.
Rate of local cerebral glucose utilization in fetal sheep was measured in conditions of normal laboratory ambient sound (65 to 70 dB sound pressure levels) and broadband noise (105 and 120 dB sound pressure levels) delivered by two earphones situated on the abdominal surface of the ewe. Broadband noise had neither a visible effect on the ewe nor specific effects on the fetal arterial pH, PaO2, PaCO2, and plasma glucose concentration. However, glucose utilization of many cerebral structures was elevated in noise-exposed fetuses.
Animals↗
Effects of cochlear ablation on local cerebral glucose utilization in fetal sheep.
Local cerebral glucose utilization was measured by the [14C]-deoxyglucose method in five near-term fetal sheep in whom bilateral ablation of the cochleae had been accomplished aseptically 5 to 8 days earlier. The tympanic membrane and ossicles were removed and all turns of each cochlea were unroofed with destruction carried to the modiolus. Mean local cerebral glucose utilization of 33 of 34 gray matter structures and four of four white matter structures in operated animals were significantly lower (p less than 0.05) than that in unoperated control fetuses. The depression in local cerebral glucose utilization was greatest (p less than 0.002) in brain stem auditory nuclei, in which the mean rate of glucose utilization was approximately 25% of the levels in unoperated fetuses. The pattern of glucose utilization in these structures was clearly altered, with a reversal of the normal distribution in density of the inferior colliculus. Tonotopic bands of high local cerebral glucose utilization frequently seen in autoradiographs of inferior colliculus in unoperated fetuses were not observed in operated fetuses. These results show that the glucose utilization of the brain, and by implication the normal growth and maturation of the brain, depends on an intact auditory system during prenatal life.
Animals↗
Custom-made vaginal balloons for strengthening circumvaginal musculature.
A technique for making individualized silicone rubber intravaginal balloons is described. The method entails investing alginate vaginal impressions in silicone rubber and casting a resin model which is then dipped repeatedly in a Silastic Dispersion (Dow Corning, Q7-2213). The range of forces developed by circumvaginal muscles during maximum contractions was determined to be 0.5-4 lbs. Pressure-volume relationships of the balloons showed that the pressure of filling fluid was an accurate replica of the mean pressure in the vagina.
Female↗