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Biomedical subjects

R Gagnon

Publications and source records attributed to R Gagnon.

At least 19 recordsLinked to original sources

Single and repeated doses of the vasodilator/beta-adrenergic antagonist, carvedilol, block cirazoline- and isoproterenol-mediated hemodynamic responses in the conscious rat.

The purpose of this study was to evaluate the effects of carvedilol, a beta 1&2-adrenergic blocker and vasodilator, on cirazoline-mediated changes in arterial blood pressure and isoproterenol-mediated changes in heart rate after acute and chronic administration. Conscious, chronically instrumented male Sprague-Dawley rats were injected with carvedilol (1 mg/kg, IV), prazosin (0.3 mg/kg, IV), or propranolol (1 mg/kg, twice daily for 8 days. After administration of the first dose of carvedilol on day 1, the vasopressor response to cirazoline (60 +/- 3 mmHg predrug) and the isoproterenol-induced tachycardia (152 +/- 13 beats/min predrug) were blocked (e.g., 7 +/- 4 mmHg postdrug and 11 +/- 3 beats/min postdrug, respectively). After the administration of carvedilol on day 8, the cirazoline vasopressor response was 2 +/- 1 mmHg and the isoproterenol-induced tachycardia was 4 +/- 3 beats/min, indicating effective alpha 1- and beta-adrenergic blockade after chronic dosing with carvedilol. Prazosin blocked the cirazoline-induced vasopressor response on both days 1 and 8 but had no effect on the isoproterenol-induced tachycardia. Propranolol blocked the isoproterenol-induced tachycardia on both days 1 and 8 but had no effect on the cirazoline vasopressor response. These data indicate that only carvedilol effectively blocked both alpha- and beta-adrenergic hemodynamic responses and that the antagonism of these responses with carvedilol was not diminished after chronic dosing of twice-a-day treatment for 8 days.

Adrenergic alpha-Agonists

Diurnal changes in the profile shape and range of motion of the back.

The diurnal height change reported to occur in young adults was investigated to characterize changes in the lumbar range of motion, spinal profile, and range of motion of the back. Twelve subjects aged 18-22 years were measured using stereophotography and standard clinical examinations in the evening and after a minimum of 8 hours of complete bed rest. The average increase in height was 20 mm. Forty percent of the height increase took place in the lumbar spine without change in the depth of the lordosis, and forty percent took place in the thoracic curve with a decrease in the kyphosis. The remaining 20% of the height increase was not located, but no measurements were taken of the cervical spine. Range of motion studies revealed that lumbar flexion, as measured using the lumbar flexion increment, was decreased in the morning, and straight leg raise was decreased when measured clinically but not when measured photographically. Extension, rotation, and femoral stretch test were not affected. The authors conclude that stereophotogrammetry offers an accurate, noninvasive way to study spinal profiles. Further work is needed to assess and quantify the relative motion of the skin and the underlying structures.

Adult

Perinatal assessment of cerebral flow velocity wave forms in the human fetus and neonate.

The temporal relationship between changes in cerebral Doppler flow velocity wave forms, ductal patency, blood gases, and blood pressure during the transition from intrauterine to newborn life was assessed longitudinally in 16 healthy term fetuses and newborns. Doppler flow velocity wave forms were obtained from fetal cerebral arteries (anterior cerebral, internal carotid, and basilar) before birth, within 8 h after birth, and again at 24 and 48 h after birth. The resistance index was used as a measure of vascular resistance. The resistance index of the cerebral arteries studied increased significantly between the antenatal and 8-h study periods. This was followed by a significant decrease below fetal levels by the 24-h study period, with little change thereafter. We conclude that in the newborn human, as in the newborn lamb, the transition from fetal to immediate newborn life is associated with an increase in cerebral vascular resistance and thus a decrease in cerebral blood flow in response to the increase in arterial oxygenation. The subsequent decrease in the cerebral resistance index between 8 and 24 h of life cannot be explained by a loss of ductal shunting nor by associated changes in newborn blood gases or blood pressure, but may rather reflect a remodeling of the circulation due to impedance matching.

Blood Flow Velocity

The fetal sound environment during vibroacoustic stimulation in labor: effect on fetal heart rate response.

Nine pregnant women near term, with medical indications for internal monitoring during labor, were studied to determine the transmission of sound across maternal soft tissues during vibroacoustic stimulation with an electronic artificial larynx. A miniaturized hydrophone was placed transcervically at the level of the fetal neck under ultrasound guidance. Intrauterine sound pressure levels were measured before and during stimulation applied at 1 and 0 cm from the surface of the maternal abdomen. When the electronic artificial larynx was placed at a distance of 1 cm from the maternal abdomen, the intrauterine sound pressure level averaged 75 dB at frequencies between 0-5000 Hz. However, when the electronic artificial larynx was firmly applied on the maternal abdomen, intrauterine sound pressure levels were enhanced by more than 20 dB (P less than .001) and averaged 95 dB at all frequencies between 87-20,000 Hz. Baseline intrauterine sound pressure levels consisted of low-frequency sound with intensity of 85 dB at 12.5 Hz, decreasing to 60 dB at 100 Hz and less than 40 dB above 200 Hz. There was a significant correlation (r = 0.78, P less than .02) between the duration of the first fetal heart rate (FHR) acceleration following stimulus and the overall intrauterine sound pressure level at the time of the stimulus. Our data suggest that a threshold of 94 dB intrauterine sound pressure level is necessary to produce a consistent FHR response during active labor.

Acoustic Stimulation

The interaction of behavioural state, heart rate and resistance index in the human fetus.

The association and possible interactions of fetal behavioural state, fetal heart rate and vascular resistance was studied in 23 healthy pregnant women between 36 and 40 weeks' gestation. Doppler flow velocity waveforms were obtained from fetal cerebral (anterior cerebral, internal carotid and basilar), descending aorta and umbilical arteries during fetal behavioural state 1F and repeated during 2F. The Resistance Index (RI) was used as a measure of vascular resistance. Decreased vascular resistance was observed in all vessels except the umbilical artery during fetal behavioural state 2F compared to 1F (P less than 0.001). A significant interaction was observed between fetal heart rate and fetal behavioural state on the RI of the vessels studied, with a greater negative slope for RI plotted against fetal heart rate in fetal behavioural state 2F (-0.00139) compared to 1F (0.00005) (P less than 0.001). We conclude that the transition from fetal behavioural state 1F to 2F is associated with a significant reduction in cerebral and systemic vascular resistance, with no apparent change in placental resistance. Furthermore, fetal behavioural state and fetal heart rate interact, demonstrating a stronger association of fetal heart rate and RI in fetal behavioural state 2F in keeping with an increase in baroreflex sensitivity at this time.

Behavior

Back pain and spinal changes in microgravity.

We believe that investigations into back pain and spinal changes in microgravity will contribute significantly to our knowledge and understanding of factors that cause back pain and the influence of spinal cord distraction on sensory and autonomic dysfunction. This information may have clinical implications for the treatment and rehabilitation of patients with spinal cord injury, for the care of patients during and after corrective spinal surgery, for the care and treatment of patients with chronic pain syndromes, and may potentially provide us with the opportunity to learn more about demyelinating diseases.

Back Pain

Behavioural assessment of fetal health.

The assessment of behavioural activity of the fetus is widely used to assess fetal health in clinical practice as part of the biophysical profile as well as the nonstress test. Considerable information regarding normal activity patterns of healthy human fetuses have been obtained from 24 to 40 weeks gestation. It is this information which has provided the scientific foundation for the development of fetal assessment protocols. Studies in chronically-catheterized fetal sheep have demonstrated that acute hypoxemia leads to an inhibition of fetal breathing movements although prolonged reductions in oxygen delivery to the fetus in the absence of acidemia are associated with adaptation by the fetus and subsequent return to normal incidence of behavioural activity. The behavioural responses of the fetus to specific stimuli including vibroacoustic stimulation have been examined in relation to gestational age as well as type of stimulus, it is proposed that fetal acoustic stimulation could possibly be used to assess fetal neurological function although prior to it being accepted as an universal method for assessing fetal health it is essential that a greater understanding of the mechanisms involved in fetal responses to sound and vibration be determined using appropriate experimental techniques.

Behavior

The care and feeding of a psychotherapy research team.

Although psychotherapy research teams have been in existence since the 1940s, one of the reasons they are not more popular is the absence of literature on how they operate. There is essentially no literature on the organization and administration of psychotherapy research teams, on the management of their everyday practical issues, decisions, and problems. In order to open the way for a dialogue on these matters, an inside view is provided of one relatively productive psychotherapy research team. The topics include the mission and goal, nature and size of the team, administrative locale, team contract, meetings and homework, leadership and decision-making, the research tape library, and what team members get from participation on the team.

Clinical Competence

The effect of maternal hyperoxia on behavioral activity in growth-retarded human fetuses.

Thirteen pregnant women who subsequently were delivered of infants with birth weights less than the 3rd percentile were studied for examination of fetal heart rate and fetal activity patients during maternal administration of oxygen at a concentration of 50% or room air for 2 hours. None of the fetuses was acidotic at birth. Maternal transcutaneous PO2 levels increased from 79 +/- 3 mm Hg to 158 +/- 10 mm Hg for the 2 hours of observation. The results indicated that maternal hyperoxia produced sustained fetal breathing activity that was almost 100% higher than that in room air (analysis of variance, p = 0.024). Gross fetal body movements, fetal heart rate accelerations, and fetal heart rate variability increased significantly with increasing observation time (analysis of variance, p less than 0.01), but were not significantly altered by maternal hyperoxia or room air. We conclude that despite significant change in fetal breathing activity, ultrasonographic observation of fetal behavioral activity during maternal hyperoxia could not be used to differentiate severely growth-retarded from normally grown human fetuses. We speculate that altered fetal heart rate and fetal body movement patterns usually associated with intrauterine growth retardation might be related to altered development of the fetal central nervous system and are not reversible during prolonged maternal administration of oxygen.

Analysis of Variance

The intrauterine sound environment of the human fetus during labor.

Ten pregnant women near term with medical indications for internal monitoring during labor were studied to quantify the intrauterine sound environment. The intrauterine background noise was measured with a miniaturized hydrophone placed transcervically at the level of the fetal neck under ultrasonographic guidance. In eight women no cardiovascular noise was audible and the intrauterine noise consisted predominantly of low-frequency noise (less than 100 Hz) from 60 to 85 dB. Above 100 Hz, the sound pressure level was less than 60 dB, decreasing to 40 dB above 500 Hz. In only two women maternal cardiovascular sounds were audible during uterine relaxation and disappeared during uterine contraction. Maternal bowel sounds and maternal vocalization were well above the intrauterine background noise. Because of this relative quietness, we hypothesized that the fetal acoustic environment could be altered significantly during antenatal vibratory acoustic stimulation.

Acoustic Stimulation

Cytotoxicity, sister-chromatid exchanges and DNA single-strand breaks induced by 4-oxo-4-(3-pyridyl)butanal, a metabolite of a tobacco-specific N-nitrosamine.

The tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is metabolized by alpha-carbon hydroxylation to reactive diazohydroxides and aldehydes. The aim of this study was to determine the relative ability of one NNK-derived aldehyde, 4-oxo-4-(3-pyridyl)butanal, to induce cytotoxicity, sister-chromatid exchanges (SCEs) and DNA single-strand breaks (SSBs) in V79 cells. Our data demonstrate that this aldehyde is cytotoxic for V79 cells (IC50 = 0.4 mM) and induces SCEs at concentrations ranging from 0.01 to 0.5 mM. DNA SSBs were observed at concentrations ranging from 0.05 to 1 mM and were repaired within 8 h. When V79 cells were cultured with primary hepatocytes, there was a reduction in the frequency of SCEs induced by the aldehyde. This suggests that hepatocytes can partially deactivate the aldehyde. Our results suggest that this aldehyde is one of the reactive intermediates generated during NNK metabolism.

Animals

Vibratory acoustic stimulation in 26- to 32-week, small-for-gestational-age fetus.

Seven pregnant women with early-onset (less than 32 weeks' gestation) intrauterine growth retardation were studied to examine fetal heart rate and fetal activity patterns after vibratory acoustic stimulation. All studies were done between 26 and 32 weeks' gestation. All fetuses but one were not acidotic at birth. There was a reduced time during which accelerations (50% less), long-term fetal heart rate variability (25% less), and body movements (60% less) occurred in small-for-gestational-age fetuses compared with these times in age-matched normally grown fetuses. Fetal heart rate and fetal activity patterns were not significantly altered after stimulation with the electronic artificial larynx. We hypothesized that severe, early-onset (less than 32 weeks' gestation), chronic nutritional deprivation of human fetuses is associated with a delay in the functional maturation of fetal sensory receptors.

Acoustic Stimulation

Relationship between fetal heart rate and umbilical blood flow velocity in term human fetuses during labor.

Fourteen pregnant women between 37 and 41 weeks' gestational age, who subsequently were delivered of healthy newborn infants, were studied to examine the effects of spontaneous changes in fetal heart rate on the flow-velocity waveforms in the umbilical artery. The women were in active labor and under epidural anesthesia at the time Doppler measurements were made. There was a significant positive relationship between end-diastolic flow velocity and fetal heart rate. The umbilical artery peak-systolic/end-diastolic ratio was best correlated with the negative reciprocal transformation of the instantaneous fetal heart rate value and end-diastolic flow velocity. No significant correlation was found between fetal heart rate, umbilical artery peak-systolic/end-diastolic ratio, and peak-systolic flow velocity. An upper limit of 3.0 for a normal umbilical artery peak-systolic/end-diastolic ratio was acceptable only if the instantaneous fetal heart rate was greater than or equal to 130 beats/min.

Blood Flow Velocity

Effect of prolonged hypoxemia on fetal heart rate accelerations and decelerations in sheep.

Experiments were conducted in 10 chronically catheterized fetal sheep to determine the effect of 24 hours of hypoxemia in the absence of progressive acidemia on fetal heart rate accelerations and decelerations. Fetal hypoxemia was produced by mechanically restricting uterine blood flow with a vascular clamp placed around the maternal common internal iliac artery. Fetal arterial oxygen tension decreased from 22.3 +/- 1.8 to 17.8 +/- 1.5 mm Hg at 2 hours and remained low for the 24-hour experimental period. Fetal pH decreased from 7.34 +/- 0.01 to 7.20 +/- 0.05 at 2 hours and returned to normal values by 12 hours. No significant change was observed in the number or characteristics of fetal heart rate accelerations or decelerations during the 24-hour control period. There was a significant increase in the number of accelerations from 48 +/- 4 to 63 +/- 4 per hour at 8 hours of hypoxemia followed by a return to control values by 12 hours. There was no significant change in the mean amplitude or duration of accelerations. There was a significant increase in the number of decelerations per hour with an associated increase in the mean amplitude but a decrease in the mean duration of decelerations during the first 16 hours of hypoxemia. We conclude that prolonged hypoxemia in fetal sheep leads to an initial increase in the number of both accelerations and decelerations in fetal heart rate followed by a return to normal patterns indistinguishable from those of the normoexemic fetus.

Animals

Fetal heart rate patterns in the small-for-gestational-age human fetus.

A total of 24 pregnant women with growth-retarded fetuses were studied to examine the distribution of fetal heart rate accelerations between 30 and 40 weeks' gestation, as compared with those of fetuses of normal growth that were matched for gestational age and length of fetal heart rate tracings. Growth-retarded fetuses had significantly lower PO2 levels in the umbilical artery at birth (3 mm Hg less) than did healthy fetuses (p less than 0.05), but without metabolic acidosis. There was a larger proportion of small amplitude (less than 10 beats/min) and a smaller proportion of large amplitude (greater than 20 beats/min) fetal heart rate accelerations in the small-for-gestational-age fetuses than in the fetuses of normal growth. Although the number of accelerations was significantly reduced (50% less) in growth-retarded fetuses compared with healthy fetuses, there was no significant difference in the mean basal fetal heart rate and the mean number of decelerations between the two groups. Currently used definition of an acceleration as greater than or equal to 15 beats/min for greater than or equal to 15 seconds was applicable only in fetuses of normal growth. We hypothesized that a decrease in absolute acceleration frequency might be a useful index to detect the chronically hypoxemic fetus before severe metabolic acidosis and irreversible damage occurred.

Blood Gas Analysis

Human fetal behavioral states after vibratory stimulation.

A total of 14 healthy pregnant women between 37 and 41 weeks' gestational age were studied to determine the effects of a 5-second external vibratory stimulus (100 Hz, square wave) on human fetal behavioral states. Fetal behavioral state observations were made with simultaneous recordings of fetal heart rate, gross fetal body movements, and fetal eye movement between 8:30 AM and 4:00 PM. During the first episode of behavioral state 1F (quiet sleep state) greater than or equal to 10 minutes duration on two consecutive half days, the vibratory stimulus was placed on the surface of the maternal abdomen over the fetal head. Each fetus received one 5-second vibratory stimulus during either the first or second half day of observation. The time at which the instrument was applied but no vibratory stimulus was administered was considered as the control period. All women were then observed for 2 hours after the control period and after stimulation. A transition period from a quiet sleep state to a stable active sleep state (state 2F, rapid eye movement sleep) averaged less than or equal to 3 minutes after stimulation, as compared with 23 minutes after the control period. These changes in fetal behavioral states persisted for 20 minutes after vibratory stimulation. There also was an immediate and sustained increase in long-term fetal heart rate variability, the number of fetal heart rate accelerations and gross fetal body movement during the first 20 minutes after stimulus, without changes in basal fetal heart rate. We hypothesize that changes in fetal behavior seen after application of low frequency vibratory stimulus are more physiologic than the profound changes in fetal heart rate and gross fetal body movement previously described after vibratory acoustic stimulation with an electronic artificial larynx.

Behavior

Effects of low-frequency vibration on human term fetuses.

Thirteen healthy pregnant women between 37 and 41 weeks' gestational age were studied to examine effects of a 5-second external vibratory stimulus (100 Hz, square wave) on fetal heart rate, fetal breathing, and gross fetal body movement patterns. All fetuses were stimulated during an episode of low fetal heart rate variability (mean minute range less than or equal to 32 milliseconds for greater than or equal to 5 minutes) lasting at least 5 minutes. There was an immediate and sustained increase in long-term FHR variability, number of FHR accelerations, and gross fetal body movements after stimulation. Fetuses made breathing movements more irregularly after vibratory stimulus. We hypothesize that external low-frequency vibratory stimulus, applied during episodes of low fetal heart rate variability, causes a change from a state of quiet sleep to a state of rapid-eye-movement sleep in healthy term fetuses.

Acoustic Stimulation