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S Ioffe

Publications and source records attributed to S Ioffe.

29 records · Page 2Linked to original sources

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↗

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↗

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↗

Effects of maternal alcohol intake and smoking on neonatal electroencephalogram and anthropometric measurements.

Anthropometric data and computerized electroencaphalogram analysis during quiet, indeterminate, and active sleep were obtained from infants of mothers of four groups: (1) heavy drinking mothers (greater than 2 ounces of alcohol per day); (2) nondrinking mothers; (3) smoking, nondrinking mothers; (4) nonsmoking, nondrinking mothers. Infants in groups 1 and 2 were matched as closely as possible for postconceptional age, sex, race, and socioeconomic status. Infants in groups 3 and 4 were matched similarly. Infants of alcoholic mothers had a significantly lower birth weight, length, and head circumference than those from the matched control group. Infants of smoking mothers had lower birth weights and lengths than infants of nonsmoking mothers, but head circumference was identical. Hypersynchrony of the electroencephalogram was seen only in "alcoholic" infants, and power spectral density analysis revealed that the average integrated power was significantly increased in quiet, active, and indeterminate sleep. The greatest increase in electroencephalogram power (212%) was seen in active sleep, and this analysis clearly separated 15 of 17 alcohol-exposed infants from the control infants. These data suggest that alcohol has a specific toxic effect on the fetal brain that is not linked with smoking habits. The neonatal electroencephalogram is affected even in the absence of dysmorphology and thus may be the most sensitive indicator of fetal alcohol toxicity.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗