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S J Knopp

Publications and source records attributed to S J Knopp.

8 recordsLinked to original sources
PubMed2001

Developmental changes in the hypoxic ventilatory response in C57BL/6 mice.

C57BL/6 mice are the strain into which most null mutations for neurotransmitters or their receptors are backcrossed. A number of these transgenic mice have recently been shown to have an abnormal respiratory phenotype; however, the postnatal development of the ventilatory response to hypoxia has not been characterized in C57BL/6 mice. The effect of 8% oxygen for 5 min was examined in mice at five periods from P1 to P30 using a body plethysmograph. Neonatal and juvenile animals from P7 to P30 showed a biphasic pattern in hypoxia in which the increase in minute ventilation achieved in the first min declined towards baseline by the fifth minute and was decreased below baseline in the first minute of return to air breathing. In contrast P1-P3 C57BL/6 mice had a sustained increase in both respiratory frequency and tidal volume and their minute volume remained above baseline on return to air. The decline in oxygen consumption, measured in the fifth minute of hypoxia, was not different in P1-P3 mice compared to P8-P10. These results suggest that the earliest response to hypoxia of the respiratory system in this strain is not characterized by a time dependent depression as seen in older animals and in species whose motor systems are relatively more developed at birth.

Aging↗
PubMed1997

Non-NMDA receptors modulate respiratory drive in fetal sheep.

1. Experiments were carried out in unanaesthetized fetal sheep to evaluate the significance of non-N-methyl-D-aspartate (non-NMDA) receptor neurotransmission in the expression of fetal breathing movements. Catheters placed in the trachea and amniotic fluid and electrodes beneath the parietal bones and in the nuchal muscle were used to monitor breath amplitude and frequency and fetal behavioural state. 2. Experiments were carried out by instillation of neurotransmitter agonists, antagonists or receptor modulators into the cerebrospinal fluid (CSF) of the fourth ventricle by means of a chronic catheter introduced through the foramen magnum. 3. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased respiratory rate in a dose dependent manner by lengthening both inspiratory time (T1) and expiratory time (T0). 4. Kainate and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) increased breath amplitude. Instillation of the antagonist 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f) quinoxaline (NBQX) prior to administering AMPA resulted in apnoea, which was not overcome by the agonist. 5. Cyclothiazide, which has been shown to prevent desensitization of AMPA receptors, caused an increase in both breath amplitude (152 +/- 73%; mean +/- S.D.; P = 0.004) and frequency (46 +/- 37%; P = 0.049). 6. These data suggest that glutamate acting at non-NMDA receptors is an essential component for the expression of fetal breathing movements, and that under resting conditions these non-NMDA receptors are desensitized following glutamate synaptic release.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

GABAergic and glutamatergic effects on behaviour in fetal sheep.

1. Studies were carried out in unanaesthetized fetal sheep at 125-135 days gestation to investigate neurotransmitters involved in behavioural state. 2. Catheters and electrodes were chronically placed to record tracheal and arterial pressure, electrocortical activity (ECoG), nuchal muscle activity and to instill drugs into the cerebrospinal fluid (CSF) of the fourth ventricle. 3. Administration of the N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphopentanoic acid (AP5) or (+)-5-methyl-10,11-dihydro-5H-dibenzol[a,d]cyclohepten-5,10- iminemoleate (MK-801) increased the incidence of fetal behaviour characterized by low voltage ECoG, nuchal muscle activity and an increase in mean arterial blood pressure from 4.1 +/- 6 to 60.6 +/- 6.2% (mean +/- S.E.M.) (AP5; P = 0.003) and from 7.6 +/- 3.6 to 50.8 +/- 7.0% (MK-801; P = 0.004; values are expressed as the percentage of each 60 min period in which the state was present). 4. The incidence of fetal breathing during periods of low voltage (LV)-ECoG and nuchal muscle activity was 83.1 +/- 5.6%. The incidence of fetal breathing during LV-ECoG associated with nuchal muscle atonia was 63.1 +/- 5.0% before AP5 or MK-801 and 64.4 +/- 9.8% after instillation of these drugs. The amplitude of fetal breaths increased from 4.0 +/- 0.3 mmHg in low voltage ECoG periods to 6.7 +/- 0.8 mmHg (P = 0.006) during periods of low voltage with nuchal muscle activity. There was no significant change in breath timing during these periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of central adenosine on brainstem blood flow in fetal sheep.

The effect of the adenosine analogue R-N6-(phenylisopropyl)adenosine (R-PIA) on blood flow to the medulla and pons was examined in unanaesthetized fetal sheep. Microspheres labelled with isotopes were used to determine blood flow before and after instillation of 0.2 or 0.5 microgram R-PIA into the cerebrospinal fluid of the fourth ventricle. Blood flow to the medulla, which had a mean value (+/- S.E.M.) of 285 +/- 41 ml min-1 (100 g)-1 during the control period, was not changed by the central instillation of R-PIA. Blood flow to the pons was also not affected. These data indicate that central adenosine, which depresses respiratory drive in fetal sheep, acts by mechanisms independent of removal of carbon dioxide from the brainstem.

Animals↗
PubMed1994

A cholinergic mechanism involved in fetal breathing during the high voltage ECoG state.

The effects of muscarinic cholinergic neurotransmission on fetal breathing was determined by administration of carbachol or carbachol plus a muscarinic receptor antagonist into the cerebrospinal fluid of the fourth ventricle in unanesthetized fetal sheep. In the hour following the instillation of carbachol (1.0 microgram), the incidence of fetal breathing in high voltage electrocortical state (ECoG) increased to 63 +/- 11.7 (SEM) percent compared to 1.2 +/- 0.9 after instillation of vehicle (Ringer solution). The cholinergic agonist increased breath amplitude from 4.5 +/- 0.4 to 10.6 +/- 1.4 mmHg. These effects were eliminated when the M1 receptor antagonist pirenzepine (50-100 micrograms) was administered with carbachol but not by antagonists which are relatively selective for M2 or M3 receptors. When administered alone, muscarinic receptor antagonists did not effect the incidence or amplitude of fetal breathing in low voltage. These data indicate that the apnea which occurs during high voltage in the sheep fetus involves an inhibition of acetylcholine acting at M1 muscarinic receptor bearing neurons.

Animals↗
PubMed1991

The effect of centrally administered adenosine on fetal breathing movements.

The central effects of the adenosine analogue L-2-N6-(phenylisopropyl) adenosine (L-PIA) on breathing movements was determined by making injections into the fourth ventricle in unanesthetized fetal sheep. Administration of 0.5 micrograms L-PIA reduced the percent time during which fetal breathing occurred from 48.0 +/- 5.2 (SEM) to 19.5 +/- 6.1. Inspiratory slope was reduced to 62 +/- 5.5 and to 43 +/- 5.7 percent of the control values when 0.2 and 0.5 micrograms L-PIA were given respectively. The effects of L-PIA on the percent time fetal breathing movements occurred and on inspiratory slope were prevented by the prior systemic administration of theophylline (plasma concentrations approximately 15 micrograms/ml). When the vehicle for L-PIA, dimethyl sulfoxide in Ringer solution was given into the fourth ventricle or when 0.5 micrograms L-PIA was given systemically, there was no effect on fetal breathing. None of these protocols resulted in a change in sagittal sinus blood pH, PO2 or, PCO2. These data indicate adenosine acts at the brain stem to depress fetal respiratory drive.

Adenosine↗
PubMed1990

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↗