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R M Abrams

Publications and source records attributed to R M Abrams.

At least 19 recordsLinked to original sources

Effect of cocaine on electrocortical activity in fetal sheep.

The effect of cocaine on the behavioral state of six fetal sheep was studied during gestational ages between 128-135 days. Two to eight days after surgery, fetuses received either a continuous 60 min intravenous infusion of cocaine HCl (33.4 mg) or saline. The infusions were preceded and followed by control periods of 102 min. Cocaine induced a disruption in fetal behavioral state cyclicity and a decrease in the amount of time spent in rapid eye movement sleep (P < 0.01) and non-rapid eye movement sleep (P < 0.05) during the infusion, but not during the recovery period. Spectral amplitude of the electrocortical activity at all three cortical locations increased within most one-third octave bands between 0.8-4 Hz and decreased within most bands between 16-25 Hz (P < 0.05) compared to controls. There were no differences in spectral amplitude between pre- and post-cocaine periods at any location over the 25 frequency bands studied (P > 0.6) except for one frequency band centered at 12.5 Hz. The effects of a one hour cocaine infusion on fetal cortical electrical activity are diffuse, but short-lived, and occur independently of changes in fetal oxygenation.

Animals

Sound levels in the human uterus.

OBJECTIVE: We sought to determine the degree to which noises and voices are attenuated or enhanced as they pass into the uterus. METHODS: In eight parturients, a hydrophone in the uterus was used to measure sound pressure levels for externally generated one-third-octave band noises, male and female voices, and the subject's voice. RESULTS: Low-frequency sounds (0.125 kHz) generated outside the mother were enhanced by an average of 3.7 dB. There was a gradual increase in attenuation for increasing frequencies, with a maximum attenuation of 10.0 dB at 4.0 kHz. Sound attenuation was slightly less if the insonation was from in front of the woman rather than behind. Intrauterine sound levels of the mother's voice were enhanced by an average of 5.2 dB, whereas external male and female voices were attenuated by 2.1 and 3.2 dB, respectively. The effect of frequency on attenuation, the differences between front and back insonation, and the differences between speakers in attenuation were all statistically significant. CONCLUSIONS: The intrauterine environment is rich with externally generated sounds. This may imply fetal risk from maternal noise exposure and may aid in understanding fetal imprinting from prenatal exposure to voices.

Acoustics

Disposition and pharmacodynamics of methamphetamine in pregnant sheep.

To determine the placental transfer of methamphetamine, its subsequent fetal disposition, and its hemodynamic effects, we administered methamphetamine intravenously to 15 pregnant ewes 3 days after placement of maternal and fetal vascular catheters. Methamphetamine crossed the placenta within 30 seconds of its administration. Although the ewes had higher peak concentrations, the fetuses' longer elimination half-life ultimately led to higher fetal than maternal methamphetamine concentrations. The ratio of fetal tissue to plasma drug concentration 2 hours after administration was highest in the lung, followed by the placenta, kidney, intestine, liver, brain, and heart. Methamphetamine caused a 54% to 63% rise in maternal blood pressure, a 20% to 37% increase in fetal blood pressure, and a drop in fetal oxyhemoglobin saturation and arterial pH. We conclude that methamphetamine, in doses at or below what is commonly abused, has effects that could be detrimental to the health of the mother and her fetus.

Animals

Effects of vibration frequency and tissue thickness on intrauterine sound levels in sheep.

Pure-tone sinusoidal mechanical vibratory stimuli ranging in frequency from 4 to 4000 Hz were applied to the ventral abdominal wall of pregnant ewes, and intrauterine sound pressure levels were recorded with a hydrophone 5, 10, 15, and 20 cm from the surface. There were significant decreases in sound pressure levels with increasing frequencies (p less than 0.0001) and increasing depth (p = 0.01). There was no significant interaction between these two variables. An electronic artificial larynx was also activated on the abdominal wall, resulting in quite high sound pressure levels (mean, 119 dB) measured 5 cm from the surface, with a significant decrease in sound pressure levels as the thickness of the intervening maternal tissues increased (p = 0.005). These results suggest that the frequency of vibratory stimulus used and the thickness of the maternal abdominal wall could influence fetal response to the vibroacoustic stimulation test by affecting intrauterine sound pressure levels.

Acoustic Stimulation

Intraabdominal sound levels during vibroacoustic stimulation.

Vibroacoustic stimulation is widely used in the United States as a test for fetal well-being, yet little information is available on the adequacy of the electronic artificial larynx that is commonly used as the stimulator. To determine whether the intraabdominal sound pressure level was dependent on the static force applied to the electronic artificial larynx, we measured the sound pressure level at a position 20 cm from the surface of the anterior abdominal wall in nonpregnant ewes. The electronic artificial larynx was pressed against the surface with three levels of static force: mild, moderate, and strong. Between mild and strong static forces there was a trend toward a reduction in sound pressure level at the fundamental frequency (85 Hz) and the overtones (170 to 1600 Hz) (p less than 0.08). To further examine the relationship between the static force of sound source against the abdomen and the intraabdominal sound pressure level, sine wave oscillations between 20 Hz and 4.0 kHz were produced with an industrial shaker. With a constant dynamic force (0.16 N) applied to the shaker across frequencies, the sound pressure level was greatest at lower frequencies (100 to 110 dB) and less at higher frequencies, above 1.0 kHz (60 to 80 dB). Consistent with the electronic artificial larynx experiments, strong application of the shaker resulted in greater transmission of sound than did mild application (p less than 0.02).

Abdomen

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

Energy metabolism.

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Adenosine Triphosphate

Vaginal blood flow during the menstrual cycle.

Six nulliparous young women slept 16 to 27 consecutive nights in a clinical research center. Vaginal blood flow was estimated from rates of removal of heat from the vaginal wall by a cooled probe inserted by the women immediately upon awakening. Plasma levels of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were determined. Measured also were vaginal temperature and systolic and diastolic blood pressures. Systematic changes during the cycle were detected for all variables except systolic blood pressure. Rising levels of estradiol during late follicular phase were not correlated significantly with vaginal blood flow rates.

Adult