Biomedical subjects

S U Hasan

Publications and source records attributed to S U Hasan.

11 recordsLinked to original sources

PubMed1992

Effect of bilateral vagotomy on oxygenation, arousal, and breathing movements in fetal sheep.

To investigate the effects of bilateral cervical vagotomy on arousal and breathing responses, we studied eight sham-operated and eight chronically instrumented unanesthetized vagotomized sheep fetuses between 136 and 144 days of gestation (term approximately 147 days). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, blood pressure, pH, and blood gas tensions. In a randomized order, fetal lungs were distended with four different O2 concentrations: 0 (100% N2), 21, 50, and 100% at a continuous positive airway pressure of 30 cmH2O via an in situ Y-endotracheal tube. Under control conditions, inspiratory time and the duration of the single longest breathing episode decreased from 598 +/- 99 (SD) ms and 24 +/- 10 min in sham group to 393 +/- 162 ms and 11.0 +/- 3.0 min in vagotomized group (P = 0.04 and 0.033), respectively. In response to lung distension with 100% N2, breathing time decreased from 44 +/- 17 to 20 +/- 18% (P = 0.045) in sham-operated fetuses, whereas it remained unchanged in the vagotomized group. In response to 100% O2, fetal arterial PO2 increased in five of eight fetuses sham-operated from 18.2 +/- 5.1 to 227 +/- 45 Torr (P = 0.0001) and in six of eight vagotomized fetuses from 18.5 +/- 4.4 to 172 +/- 39 Torr (P < 0.001). Although arousal was observed in all oxygenated fetuses at the onset of breathing, the duration of arousal was markedly attenuated in vagotomized fetuses (14 +/- 10 vs. 46 +/- 29 min in sham group; P = 0.024). Frequency and amplitude of breathing and respiratory output (frequency x amplitude) increased only in sham group (P = 0.02, 0.004, and 0.0002, respectively). We conclude that in response to lung distension and oxygenation, arousal and stimulation of breathing during active and quite sleep are critically dependent on intact vagal nerves.

Amniotic Fluid↗

PubMed1992

Arterial oxygen tension threshold range for the onset of arousal and breathing in fetal sheep.

Mechanisms for the control of episodic fetal breathing movements or the onset of continuous breathing at birth remain unknown. Lung distension with 100% O2 at a continuous positive airway pressure of 30 cm H2O may induce arousal and continuous breathing. To investigate 1) the threshold range of arterial oxygen tension (PaO2) for the onset of arousal and breathing and 2) the graded response of breathing to various levels of PaO2, we studied 10 fetal sheep between 135 and 142 d of gestation (term = 147 +/- 2 d). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, arterial pH, and blood gas tensions. PaO2 threshold was determined through an indwelling O2 sensor catheter. Fetal lungs were distended at a continuous positive airway pressure of 40 cm H2O with 100% N2 or with O2 ranging from 40 to 100% via an in situ endotracheal tube. At the onset of arousal (n = 10), PaO2, arterial carbon dioxide tension, and Hb O2 saturation increased from control values of 21.7 +/- 0.75 torr (2.9 +/- 0.09 kPa), 41.8 +/- 1.1 torr (5.47 +/- 0.15 kPa), and 52.9 +/- 2.6% to 65.6 +/- 9.6 torr (8.74 +/- 1.28 kPa), 46.9 +/- 1.3 torr (6.25 +/- 0.17 kPa), and 92.9 +/- 2.06%, respectively, whereas the pH decreased from 7.31 +/- 0.006 to 7.27 +/- 0.009 (mean +/- SEM; p = 0.001, 0.04, 0.002, and 0.001, respectively). Seven of 10 fetuses breathed continuously. In these fetuses, PaO2 and arterial carbon dioxide tension further increased and pH decreased; however, no further significant increase in Hb O2 saturation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Hyperoxemia profoundly alters breathing pattern and arouses the fetal sheep.

We have recently shown that hyperoxemia alone or combined with umbilical cord occlusion causes continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). We have not however analyzed the changes in the pattern of breathing associated with these events. To do this, we measured the changes in breathing pattern, electrocortical activity and behaviour on 29 occasions in 15 fetal sheep in late gestation. Fetuses were studied during rest, and during lung distention (about 30 cm H2O) with 100% nitrogen (control), 17% oxygen, 100% oxygen and umbilical cord occlusion. Lung distention was obtained using a high frequency oscillator (Senko Co) and in some fetuses a stroke volume of 0 to 20 cm H2O was used to keep PaCO2 near-constant. We found that lung distention with nitrogen or 17% oxygen did not alter the pattern of breathing or behaviour. In 12 out of 34 (35%) experiments 100% oxygen induced continuous breathing, PaO2 increasing to about 250 torr. In the remaining 22 experiments, PaO2 increased to about 100 torr only and breathing was not continuous but it became continuous upon cord occlusion; with occlusion there was a further increase in PaO2 to 190 torr. The increased breathing with oxygen and occlusion was associated with an increase in breathing output (integral of EMGdi x f), an increase in inspiratory drive (integral of EMGdi/Ti), and a decrease in inspiratory (Ti) and expiratory (Te) times. In ten experiments PaCO2 was kept near-constant and the magnitude of the changes remained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Clinical and physiological responses to prolonged nasogastric administration of doxapram for apnea of prematurity.

We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 +/- 102 g) received doxapram alone and 6 (BW 1,020 +/- 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 +/- 1.9 to 2.1 +/- 0.6 in infants receiving doxapram alone, and from 38.2 +/- 4.4 to 7.9 +/- 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO2 to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.

Apnea↗

PubMed1991

The ventilatory response to endogenous CO2 in preterm infants.

The measurement of the ventilatory response to inhaled CO2 is unphysiologic because the CO2 that normally stimulates breathing is endogenous (tissue or venous CO2). We took advantage of the spontaneous changes in alveolar PCO2 and ventilation occurring in preterm infants during periodic breathing to calculate the ventilatory response to endogenous CO2. This response was obtained in 20 infants and compared with those obtained using the more conventional methods of steady-state inhalation of CO2 (12 infants) and rebreathing of CO2 (11 infants); it was also compared with a transient change in alveolar CO2 obtained by inhalation of 7% CO2 in air for 10 s (CO2 "bolus"; 11 infants). All groups of infants had similar birth weight and gestational ages. To calculate the response to endogenous CO2, delta PACO2 was measured as the difference between lowest and highest PaCO2 and delta VE was the difference between the corresponding instantaneous ventilation. To adjust for circulation time, values for PACO2 were made lowest for the last breath before apnea and highest for the first breath after apnea. The coefficient of variation of the method was 8%. The slope of the ventilatory response to endogenous CO2 was 0.067 +/- 0.009 (mean +/- SE) L.min-1.kg-1.mm Hg PACO2(-1), a value greater than that using steady-state and rebreathing methods (0.038 +/- 0.004 and 0.040 +/- 0.006 L.min-1.kg-1.mm Hg PACO2(-1), respectively), but similar to that of infants inhaling a CO2 "bolus" (0.051 +/- 0.009 L.min-1.kg-1.mm Hg PACO2(-1)).(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗

PubMed1991

The effects of lung distension, oxygenation, and gestational age on fetal behavior and breathing movements in sheep.

Lung distension with 100% O2 at a continuous positive airway pressure of 30 cm H2O may induce continuous fetal breathing movements (FBM) in sheep. The objectives of this study were 1) to investigate the relative roles of lung distension and oxygenation and 2) to test the hypothesis that FBM can be induced during labor, when normally they are greatly reduced or absent. We studied 13 chronically instrumented, unanesthetized fetal sheep between 128 and 144 d of gestation (term = 147 +/- 2 d). Each fetus was instrumented to record sleep states, diaphragm electromyogram, blood pressure, arterial pH, and blood gas tensions. The fetal lungs were distended via an in situ endotracheal tube with four different concentrations of O2 (0, 21, 50 and 100%) at a continuous positive airway pressure of 10, 20 and 30 cm H2O in a randomized order. No change in any recorded physiologic variable was observed at 129 +/- 1 or 132 +/- 1 d of gestation. At 135 +/- 1 and 138 +/- 1 d, in response to a continuous positive airway pressure of 30 cm H2O and 100% O2, pH decreased (p = 0.0004 and 0.005, respectively) and arterial O2 tension increased (p = 0.004 and 0.02, respectively). However, increases in 1) breathing time, 2) breathing time/low-voltage electrocortical activity ratio, 3) duration of arousal, and 4) length of single breathing epochs were observed only at 138 +/- 1 d. Lung distension with N2 resulted in a decrease in FBM. Six fetuses were studied during labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effects of various concentrations of O2 and umbilical cord occlusion on fetal breathing and behavior.

To test the hypothesis that continuous fetal breathing could be induced by hyperoxemia alone or by hyperoxemia and umbilical cord occlusion, even in the absence of a rise in arterial PCO2 (PaCO2), we studied 18 chronically instrumented fetal sheep on 34 occasions using our window model (18). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of approximately cmH2O. Inspired N2, 17% O2, and 100% O2 were given to the fetus during one cycle each. While 100% O2 was given, the umbilical cord was occluded (balloon cuff).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

The effects of naloxone on the changes in breathing and behaviour induced by morphine in the foetal sheep.

In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.

Animals↗

PubMed1990

The effects of brain-stem section on the breathing and behavioural response to morphine in the fetal sheep.

In the unanesthetized fetal sheep the administration of morphine causes initial apnoea followed by hyperpnoea. We thought that a section of the brain at midcollicular level might separate these two effects. Therefore we sectioned the brain stem of five fetuses at 132 +/- 1 (SEM) days of gestation and compared their responses to morphine (17 experiments) with that observed in seven intact fetuses at similar gestational ages (15 experiments). Brain stem sections were confirmed morphologically and histologically. Morphine, 1 mg/kg was injected in the fetal jugular vein during low-voltage electrocortical activity (ECoG). We measured ECoG, eye movements, diaphragmatic activity, blood pressure and amniotic pressure. Sectioned fetuses before the administration of morphine had a complete dissociation between ECoG and breathing activity. With the administration of morphine we found: (i) the length of the apnoea was 139.8 +/- 15.5 min in sectioned fetuses and 17.0 +/- 5.8 min in intact fetuses (P less than 0.01); and (ii) there was no hyperpneic response in the sectioned fetus whereas the length of hyperpnoea in the intact group was 99.1 +/- 11.8 min (P less than 0.001). The results support the idea of two central distinct areas of action of morphine in the fetal brain. The absence of hyperpnoea in the sectioned fetuses suggests that neurons inhibiting the 'respiratory neurons' are located rostrally to the mid-collicular line.

Animals↗

PubMed1989

Decrease in plasma prostaglandin E2 is not essential for the establishment of continuous breathing at birth in sheep.

Depression of prostanoid concentrations by indomethacin induces continuous breathing in fetal sheep, but it is not known whether this is associated with changes in fetal behaviour. Furthermore, the relationship between changes in prostaglandin E2 (PGE2) concentration after delivery and the appearance of continuous breathing has not been examined. We hypothesized that the decrease in fetal PGE2 by infusion of indomethacin would induce continuous breathing and a change in behaviour such that the fetus should come to resemble a newborn lamb; and coinciding with the establishment of continuous breathing at birth, PGE2 concentrations would decrease to a critical level below that present in the fetus. We found that continuous breathing in fetal sheep induced by infusion of indomethacin was related to a decrease in PGE2 from 436 +/- 114 to 189 +/- 73 pg/ml (P less than 0.005) but that this was not associated with fetal wakefulness. In addition, measurements of carotid arterial PGE2 concentrations showed that the beginning of continuous breathing after birth occurred at a plasma concentration of PGE2 of 1245 +/- 260 pg/ml, a value about three times higher than the 422 +/- 53 pg/ml measured in the fetus during breathing activity. Together these findings suggest that PGE2 is not primarily involved in the establishment of continuous breathing at birth.

Animals↗

PubMed1988

Effect of morphine on breathing and behavior in fetal sheep.

To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116-141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗