Biomedical subjects

L Carmichael

Publications and source records attributed to L Carmichael.

At least 37 records · Page 2Linked to original sources

PubMed1990

Oxygen consumption in the fetal lamb during sustained hypoxemia with progressive acidemia.

To investigate the fetal ability to compensate for a sustained reduction in O2 delivery (DO2; umbilical blood flow X umbilical venous O2 content), studies were carried out on eight chronically instrumented fetal lambs made hypoxemic for 7.8 +/- 0.8 (+/- SE) h by lowering maternal inspired O2 concentration to 9-10%. After 1.7 h of hypoxemia, fetal arterial PO2 had fallen from 18.4 +/- 1.2 to 10.4 +/- 0.5 mmHg. Umbilical venous O2 content fell initially by 41.1 +/- 1.8%, but the fall in DO2 was only 23.7 +/- 5.6%, caused by a 29.3 +/- 7.9% rise in umbilical blood flow. Fetal O2 consumption (VO2) was increased significantly by 29.5 +/- 15.2%. However, fetal vascular pH (7.332-7.281) and base excess (0.5 to -4.3 meq/l) were decreased while blood lactate levels were increased (1.55-7.22 mM). With continued hypoxemia, the metabolic acidemia worsened and led to progressive declines in umbilical venous O2 content and DO2. However, VO2 was maintained at the control level until delivery had fallen by 72.5% and arterial pH was 6.843, at which time VO2 decreased by 37.5 +/- 10.7%. It is concluded that the ability of the fetus to compensate for sustained hypoxemia is limited by the progressive metabolic acidemia.

Acid-Base Equilibrium↗

PubMed1990

Blood flow and oxygen delivery to fetal organs and tissues during sustained hypoxemia.

To examine the fetal cardiovascular responses to a sustained reduction in O2 delivery (DO2), studies were conducted on 13 chronically instrumented fetal lambs (128-138 days gestation) made hypoxemic for 7.9 +/- 0.5 h by lowering maternal inspired O2 concentration to 9-10%. Fetal descending aortic PO2 fell initially from 18.0 +/- 1.0 to 10.7 +/- 0.6 mmHg, whereas pH decreased progressively from 7.326 +/- 0.006 to 6.843 +/- 0.023. Blood flow to the cerebral hemispheres, myocardium, and adrenal glands rose maximally by 110.2 +/- 22.5, 253.7 +/- 41.1, and 338.7 +/- 55.0%. Cerebral hemispheric DO2 fell progressively, whereas DO2 to the myocardium and adrenal was maintained until 7.9 h, when it fell significantly. There was also a rise in blood flow to brown adipose tissue. Blood flow to the gut and skeletal muscle was maintained, whereas flow to the spleen and kidney fell. DO2 to all these tissues fell markedly because of the progressive decline in blood O2 content. It is concluded that fetal cardiovascular function was well maintained in the face of severe hypoxemia and marked acidemia.

Animals↗

PubMed1990

Indomethacin reversal of ethanol-induced suppression of ovine fetal breathing movements and relationship to prostaglandin E2.

The effects of indomethacin on the ethanol-induced suppression of fetal breathing movements and fetal arterial plasma and cerebrospinal fluid (CSF) PGE2 concentrations and maternal arterial plasma PGE2 concentration were determined in the near-term fetal lamb. Eight conscious instrumented pregnant ewes (between 130 and 133 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight, and the fetus received 6-h intravenous infusion of indomethacin (1 mg/h per kg fetal body weight) commencing 30 min later. Serial fetal and maternal arterial blood samples (n = 8) and fetal CSF samples (n = 5) were collected at selected times throughout the 12-h study for the determination of PGE2 concentration. Fetal breathing movements were monitored continuously throughout the experimental period. Maternal ethanol infusion resulted in initial suppression (P less than 0.05) of fetal breathing movements for 2 h below pretreatment value, followed by a rapid increase in the incidence of fetal breathing movements after the onset of fetal indomethacin treatment. Fetal and maternal plasma PGE2 concentrations and fetal CSF PGE2 concentration were increased (P less than 0.05) above the pre-infusion value during the administration of ethanol and 1 h thereafter. Fetal indomethacin treatment suppressed (P less than 0.05) to undetectable levels fetal plasma and CSF PGE2 concentrations, which then became similar (P greater than 0.05) to pretreatment by 12 h. There was a positive correlation between fetal plasma and CSF PGE2 concentrations. There was an inverse correlation between the incidence of fetal breathing movements and fetal CSF PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effect of ethanol on ovine fetal and maternal plasma prostaglandin E2 concentrations and fetal breathing movements.

The effect of maternal administration of ethanol on fetal and maternal plasma prostaglandin E2 (PGE2) concentrations and fetal breathing movement was determined in the near-term pregnant ewe. Six conscious instrumented pregnant ewes (between 129 and 134 days of gestation; term, 147 days) were studied on two successive days (day 1 and day 2). On each of the two days of the experiment, there was a 1-h period of maternal infusion of ethanol (1 g ethanol/kg total body weight) or an equivalent volume of normal saline. Animals were assigned to two groups with one group (n = 3) receiving ethanol on day 1 and saline on day 2, and the other group (n = 3) receiving saline on day 1 and ethanol on day 2. Fetal and maternal blood samples were collected at selected times for blood ethanol determination (n = 2), and plasma was obtained for the determination of PGE2 concentration (n = 6). Fetal breathing movements were monitored continuously during the experimental periods. Maternal saline infusion had no effect (P greater than 0.05) on fetal breathing movement and fetal and maternal plasma PGE2 concentrations (187 +/- 25 (SEM) pg/ml and 196 +/- 32 pg/ml, respectively). Maternal ethanol infusion suppressed (P less than 0.05) fetal breathing movement below preinfusion levels for 8 h and increased (P less than 0.05) both fetal and maternal plasma PGE2 concentrations to 314 +/- 55 pg/ml and 306 +/- 25 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1989

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↗

PubMed1989

Regional blood flow change in the lamb during the perinatal period.

Regional blood flow distribution was studied with a radioactive-labeled microsphere technique in 11 unanesthetized fetal sheep (139 to 143 days' gestation). After cesarean delivery each neonatal lamb was studied at 2 and 24 hours of age. Blood flow to the cerebral hemispheres and adrenal glands decreased progressively after birth and correlated inversely with the postnatal rise in arterial oxygen content (r = -0.77, p less than 0.001 and r = -0.52, p less than 0.01, respectively). Blood flow to the gastrointestinal tract and kidneys changed little despite the known increase in blood flow from the late fetal to the early neonatal period. Skeletal muscle and brown fat blood flow were both increased when measured at 2 hours after birth, with an even greater increase in their respective oxygen deliveries presumably reflecting their increased metabolic activity with thermogenesis at this time. Variable blood flow changes are thus evident over the immediate perinatal period. In some cases these changes reflect birth-related changes in either blood gases or functional activity whereas in others the changes simply reflect a continuum from the late fetal to the early neonatal period.

Animals↗

PubMed1989

Control of fetal breathing in the human fetus between 24 and 34 weeks' gestation.

The effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements was studied in 30 healthy pregnant women between 24 and 34 weeks' gestation to determine whether gestational age influences the fetal respiratory response to alterations in carbon dioxide levels. The percent time of fetal breathing movements correlated significantly with maternal end-tidal PCO2, increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation for each of the three gestational age groups studied. However, the slope of this response for the 28- to 30-week group (3.29) and for the 32- to 34-week group (3.66), although similar to that of the term fetus, was significantly greater than that for the 24- to 26-week group (1.18, p less than 0.001). We conclude that the carbon dioxide level in the preterm fetus (as in the term fetus) is an important stimulus for the generation of respiratory movements. However, a developmental change is evident; the 24- to 26-week fetus demonstrates a decreased respiratory response to tonic carbon dioxide input. This may account for the decreased incidence of fetal breathing movements in the fetus of younger gestational age.

Carbon Dioxide↗

PubMed1989

Adrenocorticotropic hormone, cortisol, and progesterone changes in the lamb during the perinatal period.

Although the changes in circulating concentrations of adrenocorticotropic hormone, cortisol, and progesterone are well established for the fetal and neonatal lamb, there is little information on these hormones in the immediate perinatal period. We have examined the relationship between these hormones and systemic blood gas tensions and substrate concentrations in the perinatal period. Measurements were made in arterial blood of seven unanesthetized fetal sheep at 138 to 141 days' gestation during low- and high-voltage electrocortical activity. After cesarean delivery each newborn lamb was studied again at 2, 5, and 10 minutes and at 2 and 24 hours while awake. There was no correlation between fetal or maternal adrenocorticotropic hormone, cortisol, or progesterone and fetal electrocortical activity. Within 2 to 5 minutes of delivery there was a dramatic increase in neonatal immunoreactive adrenocorticotropic hormone concentrations associated with an increase in plasma cortisol. Neonatal Pao2 rose progressively, but a mixed respiratory and metabolic acidosis was evident during the first 10 minutes after delivery. This was partially corrected by 2 hours of neonatal life and was fully corrected by 24 hours of life. We conclude that rapid responsiveness of the fetal pituitary-adrenal axis occurs in response to birth in the absence of active labor, and we suggest that this may have survival value for the preterm fetus.

Adrenocorticotropic Hormone↗

PubMed1989

Effect of acute, multiple-dose ethanol on maternal and fetal blood gases and acid-base balance in the near-term pregnant ewe.

The effect of ethanol on maternal and fetal blood gases and acid-base balance was determined in six conscious instrumented near-term pregnant ewes for maternal intravenous infusion of 3 g ethanol/kg total body weight administered as six doses of 0.5 g ethanol/kg total body weight over 8 h. Maternal and fetal blood ethanol concentrations, determined in two animals, were maximal at 8 h (3.74 and 3.82 mg/mL, respectively) and were virtually identical during the 24-h study. Maternal and fetal blood gases and acid-base balance were not significantly altered during and after ethanol administration compared with preinfusion values. The data demonstrate that, during near-term ovine pregnancy, the equivalent of a binge-type drinking episode does not produce fetal hypoxia or acidosis. Furthermore, these data do not support the postulated involvement of ethanol-induced fetal hypoxia in the mechanism of ethanol teratogenesis.

Acid-Base Equilibrium↗

PubMed1989

Cerebral oxidative metabolism in lambs during perinatal period: relationship to electrocortical state.

Cerebral oxidative metabolism and regional blood flow were studied, with changes in behavioral state over the immediate perinatal period, to determine the change in cerebral metabolism at birth and the relationship to behavioral activity. Nine unanesthetized fetal sheep (139-142 days gestation) were each studied during a period of high-voltage and low-voltage electrocorticogram (ECOG) activity and then again after cesarean delivery at 2 h of age while awake and at 24 h of age while awake and during a period of high-voltage ECOG sleep. Preductal arterial and sagittal vein blood samples were analyzed for O2 content, blood gases, and pH. Blood flow was measured with a radioactive microsphere technique. Cerebral oxidative metabolism showed no significant perinatal change, although a coupling to behavioral state was evident with significant increases during both the perinatal low-voltage ECOG state and the awake state at 24 h. Blood flow to the brain showed a significant perinatal decrease after birth and state-related increases during both the prenatal low-voltage ECOG state and the awake state at 24 h consistent with the tight coupling of flow and/or O2 delivery to metabolic needs reported for normal brain tissue. The cerebral metabolic rate of the prenatal low-voltage ECOG state suggested a level of functional excitation comparable with that of the awake state after birth, supporting the importance of the rapid-eye-movement (REM) state mechanism as a source of endogenous stimulation during the perinatal period of brain growth and development.

Animals↗

PubMed1989

Development of tolerance to ethanol-induced suppression of breathing movements and brain activity in the near-term fetal sheep during short-term maternal administration of ethanol.

The effect of short-term maternal ethanol administration on the ethanol-induced suppression of fetal breathing movements, electrocortical (ECoG) activity, and electroocular (EOG) activity was determined in the near-term fetal sheep. Twelve conscious instrumented pregnant ewes (between 125 and 139 days of gestation; term, 147 days) received 1-h intravenous infusion of 1 g ethanol/kg total body weight daily for six days (n = 6) or an equivalent volume of normal saline daily for six days (n = 6). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g ethanol/kg total body weight. A further six ewes received 1-h intravenous infusion of 1 g ethanol/kg total body weight (n = 3) or an equivalent volume of normal saline (n = 3) daily for thirteen days with both groups receiving 1 g ethanol/kg total body weight on day fourteen. Fetal ECoG and EOG activities, and fetal breathing movements were monitored continuously over the post- operative and experimental periods. Saline infusion had no significant effect on the parameters studied. Fetal breathing movements were suppressed for 8 h after the first ethanol dose, and were not significantly suppressed after fourteen days of once-daily, maternal ethanol administration. Low-voltage ECoG and EOG activities were suppressed for 3 h after the first ethanol dose, and were not significantly suppressed after seven days of repeated ethanol administration. Maternal and fetal blood gases and acid-base balance were not significantly affected by maternal ethanol administration. These data demonstrate that short-term maternal administration of ethanol results in the development of tolerance to ethanol in the mature fetus.

Animals↗

PubMed1989

Indomethacin antagonizes the ethanol-induced suppression of breathing activity but not the suppression of brain activity in the near-term fetal sheep.

The effect of indomethacin on the ethanol-induced suppression of fetal breathing movements, low-voltage electrocortical (ECoG) activity, and electro-ocular (EOG) activity was studied in the near-term fetal sheep. Ten conscious instrumented pregnant ewes (between 129 and 131 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight and simultaneous fetal treatment with either indomethacin (2 mg/kg fetal body weight/h) (n = 5) or an equivalent volume of phosphate buffer (n = 5) intravenously for 9 h. Fetal ECoG activity, EOG activity, and fetal breathing movements were monitored continuously over the experimental periods. In animals treated with ethanol and buffer (n = 5), fetal breathing movements were suppressed for 8 h and low-voltage ECoG and EOG activity was suppressed for 2 h below preinfusion levels. In animals treated with ethanol and indomethacin (n = 5), fetal breathing movements were elevated for 13 h but low-voltage ECoG and EOG activity remained suppressed for 3 h below preinfusion levels. The data suggests that indomethacin can antagonize the ethanol-induced suppression of fetal breathing movements, but does not alter the ethanol-induced suppression of ECoG or EOG activity.

Animals↗

PubMed1989

Epidemiology of anencephaly in Texas, 1981-1986.

The incidence of anencephalic births among Texas residents for the period 1981 through 1986 is described. The annual incidence of this birth defect varied from 3.8 to 4.3 cases per 10,000 total births (live births and stillbirths). The highest mean annual incidence was found in East Texas and South Texas. Within all ethnic and racial groups studied, females had higher rates of anencephaly than males, and Spanish-surnamed residents had the highest incidence of this defect, with 5.0 cases per 10,000 live births. Mothers with three or more previous live births or a history of stillbirths were more likely to have anencephalic offspring than were those without these documented histories. Differences in the incidence of anencephalic births between Spanish-surnamed and non-Spanish-surnamed whites were not explained by differences in parity.

Anencephaly↗

PubMed1989

Cerebral oxidative metabolism during sustained hypoxaemia in fetal sheep.

Cerebral oxidative metabolism was determined in 9 unanaesthetized fetal sheep near term, during a normoxic control period and during sustained hypoxaemia induced by lowering maternal inspired O2 concentration to 11-8% with 3% CO2 added. Preductal arterial and sagittal vein blood samples were analyzed for oxygen content, blood gas tensions and pH. Cerebral blood flow was measured with a radioactively-labelled microsphere technique. Induced fetal hypoxaemia resulted in a metabolic acidaemia which was progressive over several h. Cerebral oxygen consumption was initially marginally decreased in response to induced hypoxaemia with cerebral blood flow increased thus maintaining O2 delivery coupled to cerebral oxygen consumption. With a worsening metabolic acidemia, pHa below 7.15, cerebral blood flow fell as mean arterial pressure fell, but cerebral oxygen consumption was little changed as fractional O2 extraction now increased. With sustained hypoxaemia and profound metabolic acidaemia, pHa below 7.00, fractional O2 extraction also fell resulting in a terminal fall in cerebral oxygen consumption to less than 50% of control values. Although the initial marginal decrease in cerebral oxygen consumption in response to induced hypoxia may represent a protective mechanism whereby the fetal brain decreases nonessential functions thus lowering oxidative needs, the terminal fall in cerebral oxygen consumption suggests pathological alterations within the brain at this time.

Animals↗

PubMed1988

Fetal heart rate and activity patterns in growth-retarded fetuses: changes after vibratory acoustic stimulation.

Seventeen pregnant women who subsequently were delivered of infants with birth weights less than the third percentile were studied for examination of fetal heart rate and fetal activity patterns before and after a 5-second external vibratory acoustic stimulation. None of the fetuses was acidotic at birth. A reduced time was noted during which accelerations in heart rate occurred (50% less) and long-term fetal heart rate variability (25% less) in small for gestational age fetuses compared with age-matched, normally grown fetuses. The incidence of gross fetal body movements was significantly lower (40% less) in small for gestational age fetuses than in those who were appropriate for gestational age. Fetal heart rate and fetal activity patterns after stimulation with the electronic artificial larynx in small for gestational age fetuses were similar to those of appropriate for gestational age fetuses.

Acoustic Stimulation↗

PubMed1988

The role of carbon dioxide in the generation of human fetal breathing movements.

To determine the role of carbon dioxide in the generation of fetal respiratory movements, the effect of induced maternal hypocapnia and hypercapnia on fetal breathing movements, gross body movements, and fetal heart rate was studied in 12 healthy pregnant women near term. Patients were studied for a 1-hour control period breathing room air followed by four randomized 15-minute study periods with patients breathing either room air, a prepared gas mixture with 2% or 4% carbon dioxide, or undergoing controlled hyperventilation as determined by monitoring end-tidal PCO2. The percentage of time fetal breathing movements correlated significantly with maternal end-tidal PCO2 (r = 0.62, p less than 0.01), increasing with maternal breathing of 2% and 4% carbon dioxide and decreasing with maternal hyperventilation. Fetal gross body movements, fetal heart rate, and fetal heart rate variability showed no significant changes. It is concluded that as in adults, the carbon dioxide level in fetuses is an important stimulus for the generation of respiratory movements, acting independent of a change in behavioral state. It is hypothesized that tonic carbon dioxide level input is an important determinant of fetal respiratory center drive, but little or no phasic carbon dioxide input exists because of continuous placental excretion, thus resulting in the episodic occurrence of breathing movements with changes in the fetal behavioral state.

Adult↗

PubMed1988

Effects of multiple-dose maternal ethanol infusion on fetal cardiovascular and brain activity in lambs.

Ethanol (2 gm/kg of maternal body weight administered in four equal doses of 0.5 gm/kg over 5 hours) was infused intravenously into nine chronically prepared pregnant ewes between 124 and 137 days' gestation. The data demonstrated a dose-response relationship between fetal arterial ethanol concentrations and the incidence of fetal breathing movements. Suppression of normal fetal electrocortical activity occurred at a low ethanol concentration and returned to control values at a time of very high arterial ethanol concentrations. This experimental model of a binge drinking episode further supports the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.

Animals↗

PubMed1988

Fetal heart rate and fetal activity patterns after vibratory acoustic stimulation at thirty to thirty-two weeks' gestational age.

Twenty pregnant women between 30 and 32 weeks' gestational age were studied to examine the effects of a 5-second external vibratory acoustic stimulus on the fetal heart rate, fetal heart rate variability, and fetal activity patterns. There was an immediate significant increase in the basal fetal heart rate for 10 minutes compared with controls. There was also a significant increase in the mean duration of fetal heart rate accelerations without any change in the number of fetal heart rate accelerations. There were no changes in long-term fetal heart rate variability, fetal breathing, and gross fetal body movements.

Acoustic Stimulation↗