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Biomedical subjects

A H Jansen

Publications and source records attributed to A H Jansen.

At least 37 records · Page 2Linked to original sources
PubMed1987

Vitamin K1 increases sister chromatid exchange in vitro in human leukocytes and in vivo in fetal sheep cells: a possible role for "vitamin K deficiency" in the fetus.

The levels of the vitamin K-dependent clotting factors are markedly lower in the human fetus and newborn than in older infants and adults. Direct measurement of vitamin K1 in cord plasma records low or undetectable levels. This phenomenon, although the norm, is referred to as vitamin K deficiency and is a significant risk factor for hemorrhage in the fetus and newborn. Sister chromatid exchange (SCE), which may be used as an index of mutagenic activity, was assayed in cultured leukocytes of placental and adult blood following phytohemagglutinin stimulation. The mean number of SCEs per metaphase in human placental blood was 3.32 +/- SE 0.219 as compared with levels of 5.13 +/- SE 0.273 in young adults (p less than 0.01), and in the presence of added vitamin K1 at a concentration of 1 X 10(-6) M the SCE increased significantly in both adult and placental cells. In vitro SCE dose response curves to K1 in the blood of fetal and maternal sheep were obtained. When five fetal sheep were given 1 mg of K1 by catheter into the femoral vein the SCE increased from 3.94 +/- SE 0.15 preinjection to 5.38 +/- SE 0.23 at 24 h postinjection (p less than 0.01). In the pretreatment fetal sheep, serum vitamin K1 was below detectable levels in all seven animals in which it was assayed and reached levels as high as 0.3 X 10(-6) M 1 h post-K1 injection. The low level of K1 in the fetus may in fact confer some biological advantage by reducing the risk of mutagenic events during a period of rapid cell proliferation.

Adult↗
PubMed1986

Stimulation of fetal breathing activity by beta-adrenergic mechanisms.

Experiments were done on chronically prepared fetal lambs, 125-135 days gestation, to test the effects of various catecholamines on fetal breathing (FB) as well as the influence of isoproterenol on the fetal respiratory response to hypoxemia. Bolus injections of epinephrine, norepinephrine, and isoproterenol (5-20 micrograms) were administered via the lingual artery or femoral or jugular vein during periods of FB activity or apnea. The effects of epinephrine and norepinephrine on FB were variable and not statistically significant. Isoproterenol produced a significant increase in FB, frequency of breathing, and mean inspiratory effort, when infused during rapid-eye-movement (REM) sleep but it failed to induce FB during non-rapid-eye-movement (NREM) sleep. The positive response during REM sleep was absent following pretreatment with 3-5 mg propranolol and after bilateral section of the sinus nerves. The effect of hypoxia on FB was tested before and during constant infusion of isoproterenol (1 microgram/min iv). A reduction of the fetal arterial PO2 by 3-10 Torr produced the characteristic depression of FB in either situation. These results indicate that the fetal carotid body chemoreceptors can reflexly stimulate FB under certain circumstances but that their effectiveness is limited by more powerful inhibitory mechanisms such as those operative during NREM sleep and hypoxemia.

Adrenergic beta-Agonists↗
PubMed1986

Effects of hypercapnia and hypoxemia on fetal breathing after decortication.

The effects of hypercapnia and hypoxemia on breathing movements were studied in 12 chronically decorticated fetal sheep, 127-140 days gestation. The fetal state of consciousness was defined in terms of activity of the lateral rectus and nuchal muscles. Arterial blood pressure was monitored. Fetal breathing was determined by integrated diaphragmatic electromyogram (EMG) and analyzed in terms of inspiratory time (TI), expiratory time (TE), electrical equivalent of tidal volume (EVT), breath interval (TT), duty cycle (TI/TT), mean inspiratory flow equivalent (EVT/TI), and instantaneous ventilation equivalent (EVT/TT). Fetal breathing occurred only during episodes of rapid-eye movements, and the response to hypercapnia consisted of an increase in EVT, TI, EVE, and EVT/TI and a decrease in the coefficient of variation of all measured parameters. Induction of hypoxia during episodes of spontaneous fetal breathing produced a decrease in the rate of breathing and an increase in EVT and TI with no change in the variability of all parameters studied. Since similar responses to hypercapnia and hypoxemia are seen in the intact fetus, we conclude that the cerebral cortex has no obvious effect on the chemical control of fetal breathing.

Animals↗
PubMed1984

Hypercapnia alters sleep state pattern.

Mild hypercapnia in the adult animal does not affect sleep pattern but more severe hypercapnia in the fetus increases the duration of REM sleep. Adult male rats were exposed daily for 2-3 h sessions at random to 6, 7, and 8% CO2 or room air. Breathing CO2 caused a 60% increase in sleep onset latency, a 28% decrease in sleep duration, but no change in percent time spent in REM. However, the duration of REM sleep episodes increased by 30%. Thus, in both fetal and adult animals severe hypercapnia appears to have a similar effect on sleep pattern.

Analysis of Variance↗
PubMed1984

Indomethacin-induced fetal breathing: mechanism and site of action.

The mechanism and site of action of indomethacin-induced fetal breathing (FB) was investigated in 26 chronically prepared fetal lambs. Indomethacin, which preferentially blocks prostaglandin production, was infused into the fetal circulation in two stages, 60 mg in 10 min and 60 mg over 7 h. Indomethacin stimulated sleep-state independent FB that was greatly reduced or abolished by infusions of prostaglandin E2 (PGE2). Infusions of nordihydroguaiaretic acid, which preferentially blocks the synthesis of leukotrienes, had no consistent effect on either fetal sleep or breathing activity when administered alone or after indomethacin. This suggests that the characteristic FB induced by indomethacin is due to inhibition of prostaglandin synthesis (PGE2) and not due to an overproduction of leukotrienes. The indomethacin effect on FB was observed in all fetuses tested including those deprived of peripheral chemoreceptor function, vagotomy, decortication, or spinal cord section at the T1 level. Complete constriction of the ductus arteriosus for many hours had no effect on FB. We conclude that inhibition of PGE2 synthesis stimulates FB by a central mechanism other than the cortex.

Animals↗
PubMed1984

ECoG and breathing activity in fetal lambs after undercut of cerebral cortex.

Reduction of cortical inhibition has been suggested as a possible mechanism for the transition from episodic fetal to continuous postnatal breathing. Twelve fetal lambs were chronically decorticated at 112-115 days gestation. Lateral rectus, neck, and diaphragmatic electromyogram (EMG), electrocorticogram (ECoG), and tracheal and arterial blood pressure were monitored after allowing 3 days for recovery. The fetal lambs were studied for 4-28 days in 2- to 4-h sessions/day. There were no episodes of low-voltage high-frequency ECoG activity. The mean duration (+/- SD) of rapid eye movements (REM) measured by lateral rectus EMG [11 +/- 7.9 min and periods of tonic activity or silence [non-REM (NREM)], 14 +/- 7.4 min] in decorticated fetuses were not statistically different from REM (12 +/- 5.1 min) and NREM (15 +/- 6.8 min) sleep periods in intact fetuses. After decortication, the percentage of time (+/- SD) occupied by different states were phasic diaphragmatic EMG activity 36 +/- 7.8%, tonic diaphragmatic EMG 21 +/- 8.6%, and diaphragmatic silence 43 +/- 14.2%. Phasic diaphragmatic EMG activity occurred together with REM, the latter being present 45 +/- 3.7% of the time. Despite decortication, between 115 and 125 days gestation ECoG changed from a trace alternans to a high-voltage low-frequency pattern. We conclude that the cerebral cortex is not responsible for apnea during fetal life. In addition, these data suggest that the cerebral cortex may normally be the source of ECoG synchrony.

Animals↗
PubMed1983

Drug-induced changes in fetal breathing activity and sleep state.

Drugs reported to stimulate fetal breathing (FB) were injected into a femoral vein of near-term fetal lambs during rapid eye movement (REM) and non-REM (NREM) sleep. The primary response to NaCN, 0.25-0.5 mg, a dose which did not flatten the electrocorticogram, was a brief burst of gasping in any sleep state. When injected during REM sleep, NaCN caused the cessation of spontaneous FB and the onset of gasping. Stimulation of FB was observed infrequently. Caffeine (10 mg) and doxapram (3 mg) frequently caused an immediate change in sleep state or arousal. The incidence of FB increased concomitantly with a change to REM sleep or wakefulness (W), but FB still ceased with the onset of NREM sleep. When administered during an episode of spontaneous FB during REM sleep, both caffeine and doxapram caused stimulation of the frequency and depth of breathing. Pilocarpine (4 mg) caused arousal and gasping followed by prolonged vigorous breathing that was dependent on intact carotid sinus nerves. Indomethacin (120 mg over several hours) did not affect sleep states but induced FB in both NREM and REM sleep. In summary, in the fetus the primary effect of NaCN is to suppress spontaneous FB and induce gasping and the effects of pilocarpine, caffeine, and doxapram are intimately related to sleep states or arousal. Indomethacin causes the conversion from episodic fetal to continuous postnatal-type breathing. These data indicate the importance of assessing fetal state of consciousness in interpreting the respiratory response to drugs.

Animals↗
PubMed1983

Chronic extracellular recording of fetal medullary neuronal activity.

A technique for chronic extracellular recording of neuronal activity in the medullary region of fetal sheep during different sleep states is described. Of 51 recorded neurones, 54% were associated with respiration, blood pressure changes, or muscle electromyograms, and 46% were nonspecific. During apnea (nonrapid-eye-movement sleep) both inspiratory and expiratory neurons had random intermittent activity. Thus apnea is not associated with tonic expiratory neuronal activity.

Animals↗
PubMed1982

Influence of sleep state on the response to hypercapnia in fetal lambs.

The effect of sleep state on the respiratory response to hypercapnia was studied in 14 chronic fetal sheep, 125-140 days gestation. Fetal PaCO2 was raised by 11 to 34 Torr by gradually increasing the maternal FICO2 to 0.09. Fetal sleep state was monitored. Fetal breathing (FB) was analysed in terms of frequency (f), tracheal pressure (TP) and ventilation equivalent (VEq) = sigma TP /min. In 16 out of 17 experiments on apneic fetuses in NREM sleep, the fetuses switched to REM sleep and in 14 instances began to breathe within 2 1/2 min thereafter. The PaCO2 at which apneic fetuses started breathing was 54.8 +/- 8.4 Torr (mean +/- SD). In 4 out of 10 trials on breathing fetuses in REM sleep the fetuses switched to NREM sleep and stopped breathing before removal of the CO2 stimulus. During REM sleep hypercapnia stimulated FB by an increase in TP and by a reduction in the number and duration of apneic pauses. It is concluded that in the fetal lamb CO2 stimulates breathing only during REM sleep and that this stimulus is superimposed on the basic mechanism that stimulated spontaneous FB during this sleep state.

Animals↗
PubMed1981

Effect of carotid chemoreceptor denervation on breathing in utero and after birth.

The influence of the carotid bodies on fetal breathing activity in utero and on the establishment of postnatal breathing was studied. The electrocorticogram, the electromyogram of the lateral rectus and postural muscles, and tracheal and arterial pressures were monitored on chronically prepared intact and carotid sinus-denervated fetal lambs. The denervated fetuses required a longer time for recovery from the operation, but thereafter the sleeping and breathing behavior was similar to that of the control group. Four of the carotid sinus-denervated fetuses were allowed to be delivered spontaneously, and all established regular postnatal respiration despite conclusive evidence of nonfunctional carotid bodies. These experiments indicate that the fetal carotid chemoreceptors are not essential for the spontaneous intrauterine breathing activity during rapid-eye-movement sleep nor for the establishment of effective breathing at birth.

Animals↗
PubMed1980

Respiratory response to somatic stimulation in fetal lambs during sleep and wakefulness.

1. The respiratory response to electrical stimulation of the nose, tail, gum and fibular nerve (nonspecific somatic stimulation) was tested in chronically instrumented fetal lambs during sleep and wakefulness. 2. The respiratory response to somatic stimulation was greatest during REM sleep, lowest during NREM sleep, and intermediate during the awake state (AW). 3. Respiratory responses could follow electrical somatic stimulation up to 2 Hz in any sleep state without changing sleep state. 4. The fetal breathing (FB) response to repetitive stimulation depended on the initial sleep state and whether or not the sleep state was affected by the stimulation. Five patterns of response were seen: a) NREM leads to NREM (initial sleep state and sleep state at end of stimulation)--FB was initiated and did not continue beyond the duration of the stimulation. b) NREM leads to REM sleep--FB was initiated and continued beyond the time of stimulation. c) REM leads to REM sleep--spontaneous FB was enhanced and continued beyond the time of stimulation. d) REM leads to NREM sleep--spontaneous FB was enhanced but did not continue beyond the time of stimulation. e) NREM, REM sleep, Awake leads to Awake--FB was initiated or enhanced and continued beyond the time of stimulation until the onset of NREM sleep.

Animals↗
PubMed1980

Sleep, wakefulness and the monosynaptic reflex in fetal and newborn lambs.

1. Electrocorticogram (ECoG), electromyogram (EMG) of the lateral rectus and antigravity muscles (neck and masseter) and breathing activity (FB) were monitored in chronically prepared fetal sheep of 125-140 days gestation and in newborn lambs up to 11 days postnatal age. 2. Awake state (AW), non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) were defined using standard criteria for ECoG, eye movements and postural muscle tone. 3. The percentage of time the fetuses spent in each state was: NREM sleep 53%, REM sleep 41.4%, and AW 5.6%. 4. Spontaneous intrauterine breathing activity occurred only during REM sleep, but 35% of REM sleep was not associated with FB. 5. Gasps (isolated deep inspirations) appeared occasionally throughout the recording and were not related to any specific sleep state or wakefulness. 6. In the fetus, the monosynaptic reflex (MSR) induced by direct electrical stimulation of the fibular nerve was enhanced by about 75% during REM sleep compared to NREM and AW. In the newborn lamb the adult pattern of suppression of MSR during REM sleep was not seen until several days after birth.

Animals↗
PubMed1980

The role of sympathetic nerves in the activation of the carotid body chemoreceptors at birth in the sheep.

Carotid body chemoreceptor afferent discharge was recorded in the sinus nerve of sheep fetuses within a few days of term, exteriorized from ewes given pentobarbitone anaesthesia, and in six newborn lambs, 7-21 h old. Chemoreceptor discharge, defined as such since it was irregular, had no relation to the heart beat and was excited by hypoxia, hypercapnia, H+ and NaCN, was recorded in only 8 out of 20 fetuses. It was abundant in both the newborn lambs and also in fetus carotid bodies studied in vitro. Although electrical stimulation of the sympathetic fibres to the carotid body excited the fetal chemoreceptors and caused a fall in carotid body blood flow, the fetal chemoreceptors still responded to natural stimuli and drugs in both fetus and lamb after the sympathetic pathway had been cut. Further, there appeared to be clear dissociation of chemoreceptor and sympathetic activation shortly after birth. These results confirm and extend earlier studies and they suggest that, although the sympathetic pathway may contribute to chemoreceptor activation at birth, other, possibly more important, factors must be involved. These are discussed.

Action Potentials↗
PubMed1975

Respiratory effects of H+ and dinitrophenol injections into the brain stem subarachnoid space of fetal lambs.

Mock cerebrospinal fluid (pH 5.37-8.38) or 2,4-dinitrophenol (DNP) (0.15-1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH.

Animals↗