PubMed Health⌕ Search

Biomedical subjects

J M Bissonnette

Publications and source records attributed to J M Bissonnette.

At least 37 records · Page 2Linked to original sources

Vascular lactic acid infusions do not alter the incidence of fetal breathing movements or their inhibition by acute hypoxemia.

Hypoxemia transiently inhibits the incidence of fetal breathing movements (FBM), but their incidence returns to normal after several hours despite maintained hypoxemia. We hypothesized that the lactic acidosis associated with prolonged systemic hypoxemia might mediate the adaptation of the hypoxemic inhibition of FBM. In sheep fetuses, the incidence of FBM was measured in a control hour and during 6 h of i.v. infusion of L-lactic acid, which raised the blood lactate concentrations to levels seen with moderate hypoxemia. FBM were observed at the same incidence as during control during each of the first 4 h (all approximately 40%). In the 5th h of lactic acid infusion, fetal hypoxemia was induced by lowering maternal inspired oxygen fraction and FBM occurred only 8 +/- 1% (SEM) of that hour. In a subsequent normoxemic recovery hour, the incidence of FBM remained below control levels. In the same animals on a different day, a similar hypoxemia induced without the acid infusion caused a comparable inhibition of FBM, but the incidence of FBM returned to the control level in a subsequent recovery hour. A moderate peripheral lactic acidosis does not blunt the inhibition of FBM evoked by acute hypoxemia and is not a likely explanation for the return of FBM during prolonged hypoxemia but actually might mediate some of the inhibition.

Acidosis, Lactic↗

Theophylline stimulates fetal breathing movements during hypoxia.

The respiratory responses to theophylline during normoxia and hypoxia were determined in 13 unanesthetized fetal sheep. Theophylline (plasma levels approximately 111 mumol/L) increased the incidence of fetal breathing movements measured over 120 min from 37.7 +/- 4.8% to 61.1 +/- 5.7% (SEM) in normoxic fetuses. In isocapnic hypoxia (arterial O2 tension approximately 1.86 kPa), theophylline increased the incidence from 20.0 +/- 6.3 to 52.0 +/- 6.1%. Theophylline also resulted in an increase in the slope of inspiration during both normoxia and hypoxia. We conclude that adenosine modulates fetal respiratory drive during normoxia and hypoxia.

Adenosine↗

The effect of electrocortical state on cerebral carbohydrate metabolism in fetal sheep.

We measured hemispherical cerebral blood flow and arteriovenous differences across the cerebral cortex for glucose, oxygen, and lactate during the two primary electroencephalographic patterns (high and low voltage) in unanesthetized, near-term fetal sheep. Oxygen consumption was 127 mumol/min/100 g brain in high voltage and was 14% higher in low voltage. Glucose uptake was 19 mumol/min/100 g and was 37% higher in low voltage. Cerebral blood flow was 112 ml/min/100 g and was 29% higher in low voltage. The glucose:oxygen quotient increased from 0.91 in high voltage to 1.08 in low voltage. There was a net lactate efflux of 3.2 mumol/min/100 g during low voltage compared to a net influx of 3.3 mumol/min/100 g in high voltage. During high voltage the fetal brain uses a small amount of lactate for oxidative metabolism. During low voltage, glucose uptake exceeds the oxygen uptake needed for completely aerobic consumption, and a portion of the energy utilized by the brain is produced anaerobically.

Animals↗

The effect of elevated blood glucose on the electroencephalogram and cerebral metabolism during short-term brain ischemia in fetal sheep.

The effect of cerebral ischemia on cerebral metabolism and the electroencephalogram was studied with and without prior glucose infusion in near-term normoxic fetal sheep. At normal blood glucose levels, the electroencephalogram decreased in amplitude during ischemia. At elevated blood glucose levels the electroencephalographic amplitude was much less attenuated by ischemia although Fast Fourier Transforms revealed a shift toward slower frequencies. Under either normal or elevated blood glucose conditions, ischemia caused cerebral oxygen consumption to decrease, glucose uptake to increase, and a net efflux of lactate to occur. Elevated blood glucose appears to help maintain electroencephalographic activity during ischemia, perhaps by fueling additional anaerobic energy production. The relationship between the electroencephalogram, brain metabolism, and brain damage remains to be defined.

Animals↗

Pregnancy loss in a small chorionic villus sampling series.

Two previous reports have suggested that the pregnancy loss rate with chorionic villus biopsy is high in the initial 100 to 300 cases. In the initial 211 cases of this study, the total pregnancy loss rate (7.1%) and losses not attributed to induced abortion or cytogenetic abnormality (2.8%) do not support this contention.

Abortion, Spontaneous↗

Effects of cephalic hypotension, hypertension, and barbiturates on fetal cerebral flood flow and metabolism.

The effect of altered perfusion pressure (cephalic arterial pressure minus sagittal venous pressure) on cerebral blood flow was examined in chronically catheterized fetal sheep under ganglionic blockade. Perfusion pressure was decreased by partial inflation of a brachiocephalic artery occluder and increased by an intravenous angiotensin II infusion. Cerebral flood flow was measured with radiolabeled microspheres. On average, 45% +/- 3% (SEM) reductions in perfusion pressure were accompanied by 49% +/- 4% decreases in cerebral blood flow. Increases in perfusion pressure of 42% +/- 3% were associated with 45% +/- 7% increments in cerebral flood flow. The cerebral oxygen consumption was not significantly altered in either case. We also investigated the effect of pentobarbital on fetal cerebral oxygen consumption and cerebral blood flow at normal and at altered perfusion pressure. At normal perfusion pressure pentobarbital caused a 27% +/- 5% decrease in cerebral oxygen consumption that was associated with a 44% +/- 4% decrement in cerebral blood flow and a slight widening of the arteriovenous oxygen content gradient. In this hypometabolic cerebral state, alterations in perfusion pressure were again accompanied by proportional changes in cerebral blood flow. Both perfusion pressure and the cerebral oxygen consumption appear to be important determinants of fetal cerebral blood flow.

Animals↗

Cerebral carbohydrate metabolism during severe ischemia in fetal sheep.

The effect of cephalic hypotension on brain metabolism was studied in 10 unanesthetized, normoxic (PaO2 greater than 17 mm Hg), late-gestation fetal lambs. Perfusion pressure (cephalic arterial minus sagittal venous pressure) was 40 +/- 1 mm Hg (SEM) during control and was reduced to 10 +/- 1 by occlusion of the Grachio-cephalic artery. Cerebral blood flow was measured with microspheres, and arterial and sagittal vein blood samples were analyzed for oxygen content, glucose, and lactate. During the occlusion, oxygen consumption decreased from 125 +/- 8 to 95 +/- 4 (p less than 0.05) (all values mumol 100 g-1 min-1), and glucose uptake increased from 20 +/- 3 to 25 +/- 1 (p less than 0.05). During the control period, there was no net lactate flux; during the occlusion, lactate excretion was 5.7 +/- 1.4 (p less than 0.005). The control glucose and oxygen uptakes demonstrated a normal 6:1 molar ratio; however, during the occlusion, 9.4 mumol 100 g-1 glucose min-1 were taken up in excess of expected aerobic glucose metabolism. If all of this glucose were anaerobically metabolized to lactate, three times the measured efflux would be produced. The transport properties of the fetal blood-brain barrier may be important factors in perinatal brain injury.

Animals↗

Effect of asphyxia on respiratory activity in fetal sheep.

Hypoxia in fetal sheep depresses respiratory activity. To determine if this effect is counterbalanced by hypercarbia we studied the effects of two levels of asphyxia produced by occlusions of the maternal uterine artery. Moderate asphyxia (PaO2 16.8 +/- 1.6 (SEM) PaCO2 48.9 +/- 1.0 torr) produced no changes in the percent time fetal breathing movements occupied each hour which ranged from 25.6 +/- 7.0 to 32.4 +/- 6.2%. However, a more marked asphyxia (PaO2 12.0 +/- 0.3, PaO2 57.0 +/- 1.6) resulted in a decrease in fetal respiratory activity to 8.7 +/- 3.7% during the first hour. This depression was sustained over the next 2 h but by the 5th hour breathing had returned to 26.2 +/- 7.3%. We concluded that hypercarbia can offset the respiratory inhibition of acute moderate hypoxia, but not that of a more marked lowering of PaO2 in fetal sheep. Severe asphyxia causes an initial inhibition of respiration which is followed by a return to normal respiratory activity.

Analysis of Variance↗

Effect of monosaccharide on dehydroascorbic acid uptake by placental membrane vesicles.

Dehydroascorbic acid (DHA), the oxidized form of vitamin C, is transported across the microvillous surface of the human placental syncytiotrophoblast by the D-glucose transporter. The existence of this mechanism suggests that maternal hyperglycemia may influence placental transfer of vitamin C. Therefore, we examined the effect of monosaccharides, equilibrated across the membrane, on the uptake of 0.5 mmol/L DHA by placental membrane vesicles. Relative to uptake in the absence of monosaccharide, the rate of DHA uptake was enhanced by up to 90% in the presence of 3-O-methyl-D-glucose equilibrated across the membrane. Comparable results were obtained with D-glucose and D-galactose. An inward-directed monosaccharide concentration gradient inhibited DHA uptake. However, with elevated equilibrium concentrations of monosaccharide, the magnitude of such uptake inhibition was reduced. Relative to DHA uptake at normal blood glucose concentrations (5 mmol/L), the results suggest that moderate maternal hyperglycemia does not alter, but that severe hypo- or hyperglycemia decreases, placental uptake of DHA from the maternal circulation.

3-O-Methylglucose↗

Acute anemic hypoxemia produces a transient depression in fetal respiratory activity.

Isovolemic anemia was produced in 11 unanesthetized fetal sheep by withdrawal of blood and replacement with saline-dextran. Fetal hematocrit fell from 36 +/- 1 to 19 +/- 1% (SE). Fetal breathing movements, which were present during 34.4 +/- 5.5% of 3 h before the anemia, occurred 10.1 +/- 5.3, 14.8 +/- 4.4, and 27.1 +/- 6.7% in the 3 h following. The anemia caused a fall in arterial O2 concentration from 8.4 +/- 0.3 to 3.6 +/- 0.1 vol% and sagittal vein PO2 fell from 15.4 +/- 0.5 to 12.4 +/- 0.3 Torr. Cerebral metabolic rate during the period of anemia was 2.9 +/- 0.1 ml.100 g-1.min-1, which was unchanged from the control value of 3.0 +/- 0.2 ml.100 g-1.min-1. Sagittal vein PCO2 (54.2 +/- 1.4 Torr) remained constant after the fetus was made anemic. We conclude that respiratory activity in the sheep fetus is depressed by anemic hypoxemia but that the effect is transient.

Animals↗

The effect of a calcium channel blocker (nifedipine) on uterine blood flow in the pregnant goat.

The purpose of this study was to analyze the changes in maternal uterine blood flow, maternal arterial blood pressure, and maternal heart rate with the intravenous administration of nifedipine in pregnant, unanesthetized pygmy goats. Bolus injections of 2.5 to 45 micrograms/kg of maternal weight were used. Uterine blood flow did not fall significantly. A transient fall in maternal arterial blood pressure occurred in the first minute after the injection, but the pressure returned to normal after 5 minutes. Maternal heart rate increased immediately after the bolus of nifedipine and returned toward the control value by 30 minutes.

Animals↗

Chorionic villus sampling: first-trimester prenatal diagnosis of partial 10q trisomy in a family with a 4/10 translocation.

Direct chromosome preparations of cells obtained through chorionic villus sampling at 8 weeks' gestation in a patient whose spouse is a balanced translocation carrier revealed a fetus with an unbalanced karyotype. Knowledge of the abnormality allowed the family to make a decision in regard to continuation of the pregnancy earlier than would have been possible with the routine procedure of amniocentesis. Although the risks of chorionic villus sampling are currently being investigated, it appears that this technique has great potential for early diagnosis, affording psychological advantages, as well as a safer termination in the event of an abnormal fetus.

Abortion, Therapeutic↗

The effect of carbonic anhydrase inhibition on breathing movements and electrocortical activity in fetal sheep.

Fetal breathing movements (FBM) indicated by repetitive negative intrathoracic pressures and biparietal electrocorticograms (ECoG) were recorded from 8 fetal sheep for 3 h before (control) and 3 h after the administration of a carbonic anhydrase inhibitor, acetazolamide. FBM and the low voltage (LV) ECoG state occurred 36 +/- 5% (SEM) and 60 +/- 3% of the control period, respectively. Virtually no FBM occurred during high voltage (HV) ECoG while in 57 +/- 6% of the LV state the fetuses were making FBM. The peak magnitude of the negative intrathoracic (tracheal) pressure deflections was 4 +/- 1 Torr. Following acetazolamide the incidence of FBM rose to 53 +/- 4% (P less than 0.01) but there was no significant change in the incidence of the LV state (58 +/- 3%). Most of the increase in the incidence of FBM remained confined to periods of LV ECoG activity so that an increased proportion of this state (88 +/- 2%, P less than 0.001) was occupied with respiratory efforts. The amplitude of the FBM also increased to 8 +/- 1 Torr (P less than 0.05). The increased incidence and depth of FBM is most likely due to an elevated hydrogen ion concentration and differs from a fetal respiratory acidosis induced by increasing the inspired CO2 fraction to the ewe in that the respiratory stimulation induced by acetazolamide is not associated with an increased incidence of the permissive LV ECoG state.

Acetazolamide↗

Monosaccharide uptake by erythrocytes of the embryonic and adult chicken.

Rates of monosaccharide uptake by adult and 10-18 day old embryonic chicken erythrocytes were quantitated. The rate of carrier-mediated, stereospecific transport decreased 28% from day 10 to day 14 of incubation and was unchanged thereafter. At no time, however, did the rate of carrier-mediated transport by embryonic erythrocytes differ significantly from that of the adult cells. The rate of transfer by simple diffusion was 3-5 fold faster in embryonic than in adult erythrocytes. Uptake by simple diffusion decreased slightly as the embryo developed. Chronic hyperoxic incubation (70% O2) had little influence on total monosaccharide uptake by embryonic erythrocytes.

3-O-Methylglucose↗

Insulin hypoglycemia, cerebral metabolism, and neural function in fetal lambs.

The effect of insulin-induced hypoglycemia on cerebral oxidative metabolism (CMRO2) was studied in nine late gestational fetal lambs using the radiolabeled microsphere technique for cerebral blood flow and brachiocephalic to sagittal sinus blood O2 content differences. After 4 h insulin infusion to the fetus, arterial glucose fell from control levels of 0.96 +/- 0.11 (SE) to 0.69 +/- 0.09 mmol X l-1. CMRO2 was reduced from 199 +/- 23 to 155 +/- 22 mumol X 100 g-1 X min-1 (P less than 0.05), and cerebral glucose uptake fell from 31 +/- 4 to 25 +/- 4 mumol X 100 g-1 X min-1 (P less than 0.02). During both euglycemia and hypoglycemia, 6 mumol glucose were taken up for each micromole of O2, indicating that glucose was the sole metabolic substrate for oxidative metabolism. Although there was no change in fetal electrocortical activity during the hypoglycemia, fetal breathing movements were present only 19.4 +/- 3.4% of the hypoglycemic hours compared with 36.8 +/- 2.6% of the control period (P less than or equal to 0.01). These results suggest that during rapidly induced fetal hypoglycemia, blood-brain barrier transport of glucose can limit cerebral glucose and O2 uptake, and this decrease in cerebral metabolism is associated with a lowered incidence of fetal breathing movements.

Animals↗

Monosaccharide transport into hemocytes of a sipunculan worm Themiste dyscrita.

The hemerythrin-containing blood cells, or hemocytes, of the sipunculan worm Themiste dyscrita were found to have a stereospecific and nonconcentrative monosaccharide transport system. The transport system transferred both D-glucose and 3-O-methyl-D-glucose (3-OMG), and transport into cells by this system was rapid, reaching 50% equilibrium in approximately 20 s at 10 degrees C with an initial concentration gradient of 0.1 mM; the contribution to total uptake by simple diffusion was very small. 3-OMG uptake showed saturation kinetics with a low half-saturation constant (Km less than or equal to 0.1 mM). The uptake of labeled 3-OMG by the hemocytes was strongly inhibited by unlabeled 3-OMG, 2-deoxy-D-glucose, alpha- and beta-D-glucose, D-galactose, and D-mannose. It was moderately inhibited by D-xylose, only slightly by alpha-methyl-D-glucoside and D-fructose, and uninhibited by sucrose, L-glucose, or D-sorbitol. Phloretin was more potent than phloridzin in blocking entry of 3-OMG. Cytochalasin B did not bind tightly to the T. dyscrita transporter and was not a potent inhibitor of transport; it half-maximally inhibited 3-OMG transport at 0.1 mM. Therefore, despite some differences the data suggest functional similarities in the mechanism of monosaccharide transport into blood cells of mammals and this invertebrate.

3-O-Methylglucose↗

Effect of acute hypoglycaemia on cerebral metabolic rate in fetal sheep.

Studies were carried out in 11 fetal sheep four days after surgery for insertion of catheters and electrocortical leads. After a 3 h control period an insulin infusion was given to the ewe and maintained for the next 4 h. Fetal arterial glucose fell from 0.85 +/- 0.10 to 0.57 +/- 0.06 mM (SEM) while oxygen content was unchanged (3.80 +/- 0.24 to 3.75 +/- 0.21 mM). Cerebral uptake of oxygen and glucose were determined from samples drawn simultaneously from the axillary artery and sagittal vein and cerebral blood flow (microsphere technique). There was no significant change in uptake of either oxygen or glucose by the fetal brain. We conclude that a rapid fall in fetal glucose levels with no change in oxygen content does not result in decrease in cerebral metabolism measured over a short term.

Animals↗

The effect of indomethacin on breathing movements and cerebral blood flow and metabolism in the fetal sheep.

Indomethacin, a cyclo-oxygenase inhibitor, stimulates virtually continuous breathing movements in the fetal sheep. We measured blood flow (radioactive microsphere distribution) to major brain regions and analyzed arterial and sagittal vein blood samples for oxygen and carbon dioxide tensions, pH and for oxygen contents and glucose concentrations in 13 fetal lambs between 122-132 days of gestation. The measurements were done before and again after 4 to 5 h of an indomethacin infusion. We found that indomethacin caused a mild arterial acidosis and hypoxemia and a 23 +/- 6% (SEM, P less than 0.01) decrease in blood flow to the cerebral hemispheres. Similar decreases were also observed in all other brain regions except for the cerebellum. Arteriovenous concentration differences for both oxygen and glucose widened such that there was no significant change in cerebral metabolism. Sagittal vein hydrogen ion concentration was 44.3 +/- 0.06 nmoles 1(-1) during control and rose by 4.5 +/- 1.4 nmol.1(-1) (P less than 0.01) with the indomethacin. These results are consistent with the hypothesis that one mechanism by which indomethacin augments the incidence of fetal respiratory efforts is by stimulating central chemoreceptors.

Animals↗