Neuronal adaptation in the hippocampus induced by long-term ethanol exposure.
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Animals↗
Biomedical subjects
D W Walker
Publications and source records attributed to D W Walker.
Cardiovascular, metabolic and endocrine effects of chemical sympathectomy and of adrenal demedullation in fetal sheep.
A procedure in fetal sheep for causing peripheral sympathectomy by regular intravascular guanethidine sulphate administration and for causing adrenal demedullation by intragland injection of acid formalin is reported. Demedullation substantially removed adrenaline from the fetal circulation, but has a small effect only on noradrenaline. Plasma noradrenaline levels were depressed by 50% when demedullated fetuses were also subject to peripheral sympathectomy by guanethidine sulphate treatment. This provides some evidence that the paraganglia in the sheep fetus contributes to resting plasma catecholamines. Furthermore the ability of adrenal demedullation to increase markedly this pool of extra-adrenal chromaffin tissue indicates that in the fetus adrenal activity regulates the growth of these para-aortic bodies. In response to sympathectomy plasma vasopressin concentrations rose substantially, whilst adrenal demedullation caused a small rise. Demedullation and sympathectomy depressed fetal plasma glucose and elevated plasma cortisol. In both sympathectomised and adrenal demedullated fetuses resting heart rate and blood pressure was not depressed. However in those with a depleted peripheral nervous system periods of cardiovascular instability were apparent after 2-3 days of treatment with guanethidine sulphate. Hence there were regular episodes where fetal blood pressure and heart rate fell sharply followed 60-90s later by very large increases in blood pressure sustained for up to 10 min and associated with substantial production of plasma vasopressin and catecholamines. These results show that fine cardiovascular control in the fetus requires an intact sympathetic system as the endocrine system is too slow responding to effectively maintain reflex vascular control.
Adrenal Medulla↗
Chronotropic and inotropic effects on atria of chronic ethanol ingestion in the aging rat.
Both aging and chronic ethanol consumption have been correlated with reduced cardiac chronotropic and inotropic function. This study tested the hypothesis that aging potentiates the negative cardiac effects of chronic ethanol consumption. Using isolated tissue techniques we assessed baseline and maximum automaticity and tension development in atria from 4 groups of Fischer-344 rats (young normal, young ethanol, old normal, old ethanol). Baseline and maximum rate was depressed by aging and further depressed by chronic ethanol ingestion. Baseline and maximum tension was depressed only by aging plus chronic ethanol ingestion.
Aging↗
The nucleotide and derived amino acid sequence of human apolipoprotein A-IV mRNA and the close linkage of its gene to the genes of apolipoproteins A-I and C-III.
Both cDNA and genomic clones encoding human apolipoprotein (apo-) A-IV have been isolated and characterized. Southern blot analyses of apo-A-IV gene-containing cosmids revealed that the apo-A-IV gene is linked to the apo-A-I and apo-C-III genes within a 20-kilobase span of chromosome 11 DNA. The apo-A-IV gene is located about 14 kilobases downstream from the apo-A-I gene in the same orientation, with the apo-C-III gene located between them in the opposite orientation. The nucleotide sequence of the corresponding human apo-A-IV mRNA was determined, and the derived amino acid sequence showed that mature plasma apo-A-IV contained 376 residues. Throughout most of its length, human apo-A-IV was found to contain multiple tandem 22-residue repeated segments having amphipathic, alpha-helical potential. Amino acid substitutions within these homologous segments were generally conservative in nature. A comparison of the sequences of human and rat apo-A-IV revealed a 79% identity of amino acid positions in the amino-terminal 60 residues and a 58% identity in the remainder of the sequences, with the human protein containing 5 extra residues near the carboxyl terminus. An examination of the distribution of apo-A-IV mRNA in different tissues of the rat, marmoset, and man showed that apo-A-IV mRNA was abundant in both the liver and small intestine of the rat, but abundant in both the liver and small intestine of the marmoset and man. It was expressed in only trace amounts in all other tissues that were examined. These findings on the structure and expression of apo-A-IV and the close linkage of its gene to those of apo-A-I and apo-C-III suggest a regulatory relationship between the three genes.
Amino Acid Sequence↗
Effect of hypoxemia on plasma catecholamines in intact and immunosympathectomized fetal lambs.
Fetal lambs treated with sheep anti-mouse nerve growth factor antibodies (anti-NGF) at 80 days gestation subsequently showed a diminished cardiovascular response to intravenous infusion of tyramine (1 mg/min over 10 min) and no significant change in plasma norepinephrine concentrations as measured by reversed-phase high-pressure liquid chromatography and electrochemical detection. At autopsy at 135 days gestation, catecholamine content of the heart, thyroid, kidney, and ileum was reduced by greater than 70% compared with age-matched control fetuses. The anti-NGF-treated fetuses were thus judged to have impaired sympathetic function. When made hypoxemic (arterial PO2 12-14 Torr) for 1 h at 120 or 130 days gestation, anti-NGF-treated fetuses showed no significant change of arterial pressure, heart rate, or plasma catecholamines, whereas control fetuses showed bradycardia, a 28% increase in arterial pressure, and a 670% increase of plasma norepinephrine concentrations. These results suggest that the increase of arterial pressure that occurs during hypoxemia in fetal lambs between 120 and 135 days gestation is attributable to increased activity of the peripheral sympathetic nervous system. The adrenal medulla appears to contribute to the plasma catecholamine pool at rest, but the lack of increased plasma catecholamines during hypoxia after anti-NGF implies that the adrenal medulla was unable to release catecholamines. Possible reasons for this are discussed.
Animals↗
Effect of beta-endorphin on fetal breathing movements in sheep.
It has been suggested that endogenous opioids, such as beta-endorphin (beta-EP), act to depress respiration in the fetus and newborn. We have investigated the effect of infusing beta-EP either intravenously or into a lateral cerebral ventricle on breathing movements and electrocortical activity in eight fetal lambs between 116 and 133 days gestation. Intravenous infusion of beta-EP (200 or 500 micrograms over 1 h) increased plasma beta-EP concentrations 2- to 230-fold and was associated with a small decrease in the percent time spent breathing, from 57.8 +/- 9.1 to 51.3 +/- 8.2%/h (n = 6 exp). There was no change in the amount of high- or low-voltage electrocortical activity. Intracerebroventricular beta-EP infusion (1 or 2 micrograms beta-EP/min for 120 min) was not associated with any change of breathing movements (n = 5 exp) during the period of the infusion. However, in four experiments, in the 6-h period after the end of the beta-EP infusion there were episodes of 2-4 h when the percent time per hour spent breathing exceeded 70%. Electrocortical activity increased in amplitude and distinct episodes of high- and low-voltage activity were sometimes lost in these experiments. We conclude that high concentrations of beta-EP in plasma or cerebrospinal fluid do not totally suppress fetal breathing directly in the fetal lamb.
Animals↗
Cannulation of the utero-ovarian vein in intact ewes: hormone concentrations and blood gas levels during the oestrous cycle and early pregnancy.
A technique for implanting and maintaining catheters in both utero-ovarian veins (UOV) of intact, conscious sheep has been developed. Both UOV catheters remained patent for more than 2 weeks in 72.7% of animals. In non-pregnant ewes, large pulses of PGF2 alpha were observed in UOV plasma collected on days 13 to 16 of the cycle (frequency 1.3 +/- 0.2/12 h; pulse height range 1.0-26.9 ng/ml). In contrast, on days 13 to 16 of gestation, significantly (P less than 0.001) fewer pulses of PGF2 alpha (frequency 0.42 +/- 0.2/12 h) were observed in both UOVs of pregnant ewes, which were significantly (P less than 0.001) smaller in amplitude (pulse height range 1.4-4.9 ng/ml). The maintenance of the corpus luteum (CL) during early pregnancy may therefore directly result from a decreased uterine PGF2 alpha release. During the luteal phase (day 4-12), the PO2 of UOV blood draining an ovary containing a CL (UOV/CL) was significantly higher than blood in the contralateral UOV (P less than 0.001). By days 15 and 16 of the cycle, the PO2 of UOV/CL blood had decreased and was not significantly different to that observed in the contralateral UOV (P greater than 0.1). On day 17, the PO2 of blood in both UOVs was elevated significantly compared to levels observed on the two preceding and the two following days (P less than 0.001). We consider that the higher PO2 in UOV/CL blood resulted from a very high luteal blood flow, and that the decrease on days 15 and 16 of the cycle resulted from a decline in luteal blood flow during luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Inhibition of breathing movements in fetal life: relevance to the sudden infant death syndrome.
Fetal breathing movements are discontinuous and are inhibited by neural mechanisms associated with the development of non-rapid eye movement sleep. Sudden reduction of arterial PO2 also reduces the incidence of breathing movements in the fetus. Recent work which is directed towards identifying the control pathways and neurotransmitters involved in these effects is discussed. The possibility that breathing may also be inhibited in certain situations after birth is addressed, particularly in relation to the ability of hypoxaemia to produce behavioural arousal in the normal newborn infant, but not in fetal life.
Animals↗
Effects of hyperthermia on fetal breathing movements.
High environmental temperature is known to impair fetal growth and development. We now report long lasting changes in fetal breathing activity following the exposure of pregnant ewes to an ambient temperature of 43 degrees C for 8 h. In 16 trials in 10 ewes (119-138 days gestation) heat exposure increased maternal and fetal core temperatures 1.5-2.0 degrees C, and the hyperventilation by the ewe produced a fall in fetal PaCO2 from 53.5 +/- 1.3 to 34.8 +/- 5.3 mmHg (P less than 0.05). Fetal breathing movements decreased in incidence during the hyperthermia but remained episodic (present during low-voltage electrocortical activity) with occasional brief episodes of breathing at high rates (greater than 4 breaths/s). However, 1-2 h after the end of heating, when maternal and fetal core temperature and PaCO2 had returned to normal, fetal breathing movements became continuous, and were augmented 30-100% in amplitude. Fetal breathing movements occurred during both low- and high-voltage electrocortical activity. The results show that a heat load similar to that experienced by sheep in sub-tropical regions in the summer months cause prolonged changes in the central regulation of fetal breathing.
Animals↗
The effects of raising intracranial pressure on breathing movements, eye movements and electrocortical activity in fetal sheep.
Extra-dural or cerebroventricular intracranial pressure was measured in 7 unanaesthetized fetal sheep (123-137 days gestation). Basal intracranial pressure was 6.7 +/- 1.7 mmHg, but there were many transient increases of pressure in association with spontaneous changes of amniotic pressure, fetal intrathoracic pressure, and particularly when the fetal nuchal muscles were active. These spontaneous increases of intracranial pressure were often associated with cessation of breathing movements and change of the electrocorticogram from low to high voltage activity. To test whether increased intracranial pressure influenced breathing movements and electrocortical activity, intracranial pressure was raised either by occluding the superior vena cava for 1 min with an implanted extravascular cuff, or by extra-dural injection of 0.3-1.0 ml of 0.9% NaCl. Increasing the intracranial pressure 5-15 mmHg by either method during low voltage electrocortical activity caused cessation of breathing movements, electro-ocular activity, and change of the electrocorticogram from low to high voltage in a significant proportion of trials. We propose that natural fluctuations of intracranial pressure caused by compression of the fetal body or skull, by body movements or by uterine activity, may cause changes in electrocortical activity and breathing movements.
Animals↗
The three-dimensional morphology of afferent terminal fields in the rat dentate gyrus: periodic variation.
The laminated afferent terminal fields in the rat dentate gyrus molecular layer exhibit differential histochemical staining properties. Dependent variables (e.g., field geometrics, stain intensity) based on this organization can allow evaluation of the effect of independent variables upon the integrity of each afferent, but anatomically justifiable procedures for matching measurement regions across animals are necessary. We describe such a procedure and a serendipitous observation on the normal organization of the terminal fields. From a 10 X 10 mediolateral X anteroposterior array of measurement points per animal, it was determined that each afferent field, and the total molecular layer, exhibits periodic variation in width relative to the granule cell layer. Thus, to reduce statistical variability, either a high dependent variable sampling rate, or sampling within a region of naturally low variability, is suggested. Evidence for such a region is presented, and possible consequences of this novel topology of afferentation are discussed.
Afferent Pathways↗
Lack of long term effect of p-chlorophenylalanine on brain 5-hydroxytryptamine and electrocortical activity in conscious fetal sheep.
Daily infusion of p-chlorophenylalanine (p-CPA) into unanesthetized fetal sheep for 3-6 days did not reduce brain 5-hydroxytryptamine (5-HT) concentrations or produce long-term changes in the pattern of electrocortical activity.
Animals↗
Peripheral and central chemoreceptors in the fetus and newborn.
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Animals↗
Effect of hypoxia on the excitability of two cranial reflexes in unanaesthetized fetal sheep.
In fetal sheep acute hypoxia causes a decreased incidence of breathing movements and motor activity, and the excitability of polysynaptic reflexes in the hindlimbs is depressed. To determine whether this inhibitory effect extends to other areas in the fetal CNS, we have studied the effect of hypoxia on two reflexes with cranial pathways. The digastric (jaw opening) reflex was elicited by stimulation of the dental nerve through a pair of stainless steel electrodes implanted into the mandible (4 fetuses). The thyroarytenoid muscle of the larynx was reflexly activated by stimulation of the superior laryngeal nerve by a cuff electrode (4 fetuses). Low level stimulation at 1.5-2 X threshold was repeated at approximately 2 min intervals for 3-4 h; the stimulation did not alter the pattern of electrocortical activity, breathing movements, or cause arousal. The amplitude of the digastric reflex was greatest during low voltage electrocortical activity; conversely, the amplitude of the thyroarytenoid reflex was greatest during high voltage electrocortical activity. Isocapnic hypoxia lasting 30-60 min (16 trials), in which the PaO2 was reduced to 12-14 mmHg, did not reduce the amplitude of either reflex. The reduction of thyroarytenoid reflex amplitude which normally occurred during low voltage electrocortical activity was not present during hypoxia. These experiments show that the inhibitory effects of hypoxia on spinal reflexes, breathing movements and motor activity do not include these cranial pathways.
Animals↗
Brain mechanisms, hypoxia and fetal breathing.
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Animals↗
Portal vein thrombosis shown by ultrasonography.
While alcoholic cirrhosis is the most common cause of portal hypertension and associated gastrointestinal bleeding, portal vein occlusion can produce similar clinical manifestations. Ultrasonography is an accurate, noninvasive procedure for detecting portal vein thrombosis and distinguishing infrahepatic venous obstruction from intrahepatic obstruction due to cirrhosis.
Abdominal Injuries↗
Breathing in fetal lambs: the effect of brain stem section.
The effects of section of the brain stem caudally (through the upper pons or mid-collicular) or rostrally (through the caudal hypothalamus or anterior commissure-suprachiasmatic nucleus) were studied in fetal lambs from 118 days gestation, after recovery in utero. In lambs sectioned caudally, breathing movements and electrocortical activity were dissociated. After some days recovery breathing tended to become continuous, with an abnormal prolongation of inspiratory time. Isocapnic hypoxia caused an increase in the rate and amplitude of breathing. After carotid denervation hypoxia still caused an increase in the amplitude of breathing. In lambs sectioned rostrally, there was also dissociation between breathing movements and electrocortical activity. Breathing remained episodic, with an incidence similar to that of intact fetal lambs. In two lambs after 10 days of recovery the breathing and electrocortical rhythms returned, from time to time, to their normal phasic relationship. Isocapnic hypoxia caused a diminution or arrest of breathing, as in intact lambs. The cardiovascular effects of transection were examined. Baroreflex sensitivity was normal in those lambs sectioned caudally and enhanced in those sectioned rostrally. It is concluded first that as a result of rostral section, independent episodic rhythms of fetal breathing and electrocortical activity can be dissociated. Secondly, moderate isocapnic hypoxia causes arrest of fetal breathing indirectly, requiring the integrity of a suprapontine mechanism. And thirdly, after caudal section of the brain stem, hypoxia causes enhancement of fetal breathing efforts, independently of the carotid chemoreceptors. Possible mechanisms are discussed.
Animals↗
Effect of hypoxia on polysynaptic hind-limb reflexes of unanaesthetized fetal and new-born lambs.
Polysynaptic reflex excitation of the hind-limb flexor muscles was produced by stimulation of the distal peroneal or common sciatic nerve in ten fetal and six new-born unanaesthetized lambs. In the fetal lambs, stimulation at 1.1-3.25 times threshold for direct activation of the nerve produced a reflex response which was greatest during high-voltage electrocortical activity, being reduced 69 +/- 5.0% (mean +/- S.E. of the mean) during low-voltage electrocortical activity. Reduction of the fetal arterial PO2 from 23.3 +/- 0.58 to 12.2 +/- 0.4 mmHg caused a rapid and reversible reduction of the reflex in all fetal lambs with intact spinal cord, including two whose brain stems were transected at the level of the colliculi. Hypoxia did not alter the amplitude of the reflex in two fetuses in which the spinal cord at L1-2 had been cut several days previously. In new-born lambs reduction of the arterial PO2 to 43 mmHg did not change the reflex amplitude during episodes of quiet wakefulness or slow-wave sleep. Brief reduction of the Pa,O2 to 20-30 mmHg caused a statistically insignificant reduction of reflex amplitude during quiet sleep before behavioural arousal. It is concluded that hypoxaemia activates reticular mechanisms in the pons and medulla of fetal lambs which decrease the excitability of spinal reflex pathways. In the new-born lamb such effects are counteracted or prevented by mechanisms associated with arousal.
Animals↗