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Biomedical subjects

L Bennet

Publications and source records attributed to L Bennet.

At least 55 records · Page 3Linked to original sources
PubMed1998

The cerebral hemodynamic response to asphyxia and hypoxia in the near-term fetal sheep as measured by near infrared spectroscopy.

This study examined the hypothesis that the cerebrovascular response to asphyxia of the late gestation sheep fetus is characterized by an increase in cerebrovascular resistance and a fall in cerebral blood flow (CBF) rather than the fall in resistance and increase in CBF which occurs in acute hypoxemia. In eight unanesthetized late gestation fetal sheep (123- to 125-d gestation) we evaluated continuous changes in carotid blood flow (CaBF) as an index of global CBF and total cerebral Hb concentrations as an index of global cerebral blood volume (CBV) using ultrasound flow probes and near infrared spectroscopy respectively. Asphyxia was induced by rapid and complete occlusion of the umbilical cord for 10 min. We also examined the fetal response to 1 h of acute 9% isocapnic hypoxia for comparison purposes. During hypoxia we observed a sustained increase in CaBF (p < 0.05) and CBV (p < 0.01) and a fall in carotid vascular resistance (p < 0.05). During asphyxia there was no significant rise in CBV, a fall in CaBF (p < 0.05), and a rise in carotid vascular resistance (p < 0.01). CaBF fell at a time when mean arterial pressure was elevated (p < 0.01). These data strongly suggest that fetal CBF does not increase and may even fall during severe asphyxia of rapid onset. Furthermore, our near infrared spectroscopy data show that the relative changes in total cerebral Hb concentrations may reflect the type and severity of the insult to which the fetus is exposed.

Animals↗
PubMed1997

The effect of carotid sinus denervation on fetal heart rate variation in normoxia, hypoxia and post-hypoxia in fetal sheep.

OBJECTIVE: To investigate whether carotid sinus nerve reflexes are linked to the increase in heart rate variation in acute (one hour) hypoxia in late gestation fetal sheep DESIGN: Comparison of short term variation between intact and carotid sinus denervated fetuses in normoxia, hypoxia and post-hypoxia. SUBJECTS: Sixteen chronically catheterised pregnant sheep in late gestation. RESULTS: There was no significant difference in short term variation between intact and denervated fetuses in normoxia. In intact fetuses short term variation increased significantly in hypoxia. In denervated fetuses it tended to increase in hypoxia, but this was not statistically significant. During the post-hypoxia period, short term variation increased significantly in denervated fetuses, although at this time it was decreasing in intact fetuses. When the decrease in pH was small intact fetuses showed a significantly greater increase in short term variation than denervated fetuses in hypoxia. In contrast, short term variation increased similarly in both groups when the pH decrease was greater (> 0.03 in early hypoxia and > 0.05 in late hypoxia). CONCLUSIONS: Carotid sinus nerve reflexes have an important influence on heart rate variation in hypoxia and post-hypoxia. It appears that other mechanisms (e.g. a rise in circulating catecholamines) are linked to an increase in heart rate variation when mild acidemia occurs in hypoxia.

Animals↗
PubMed1997

The role of carotid chemoreceptors in the effects of hypoxia on renal blood flow in the late gestation sheep fetus.

Previous studies of the effect of hypoxia on fetal renal haemodynamics have demonstrated a fall, a rise or no change in renal blood flow (RBF). The underlying mechanisms are not understood but involve a balance between neural vasoconstrictor and opposing vasodilator mechanisms. Since carotid chemoreflex mechanisms contribute to vasoconstriction in other fetal vascular beds and in the adult renal vasculature, we examined their effects on RBF during 1 h of acute hypoxia in late gestation fetal sheep (n = 12). Renal blood flow was measured continuously and urine collected at 15 min intervals. Seven fetuses underwent bilateral section of the carotid sinus nerves (CSD fetuses). During hypoxia CSD fetuses showed a transient initial rise in RBF (P < 0.05) and then a subsequent fall (P < 0.05) to levels comparable with that recorded in intact fetuses. There was no change in urine output in either intact or CSD fetuses during hypoxia. Thus the initial fall in RBF during hypoxia is a carotid chemoreflex but other mechanisms, e.g. vasoconstrictor hormones, contribute to the sustained response.

Animals↗
PubMed1996

The role of nitric oxide synthesis in cardiovascular responses to acute hypoxia in the late gestation sheep fetus.

1. In fetal sheep (123-129 days gestation) we investigated the effect of acute isocapnic hypoxia (Pa,O2, 12 +/- 0.6 mmHg) on the fetal heart rate (FHR), mean systemic arterial blood pressure (MAP), carotid blood flow (CBF), femoral blood flow (FBF), carotid vascular resistance (CVR) and femoral vascular resistance (FVR) with the infusion of either the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or saline vehicle. 2. During normoxia, CBF was lower (P < 0.05) and MAP, FVR and CVR were higher with L-NAME than with vehicle infusion (P < 0.01, P < 0.05 and P < 0.01, respectively). FHR fell 15 min after the onset of L-NAME infusion (P < 0.05). During hypoxia in both groups, FHR showed an initial rapid fall (P < 0.05) and subsequent return to prehypoxic levels, and there was a fall in FBF (P < 0.01). MAP increased during hypoxia with vehicle (P < 0.05) but not L-NAME infusion: thus MAP was similar during hypoxia in the two groups. The rebound tachycardia seen during recovery in the vehicle group (P < 0.01) was not evident in the L-NAME group. The rise in CBF and fall in CVR during hypoxia with vehicle (P < 0.01 and P < 0.05, respectively) was absent with L-NAME infusion. FVR rose during hypoxia in both groups (P < 0.05). 3. Thus NOS inhibition alters basal systemic vascular tone in the late gestation fetus. The rise in CBF and fall in CVR during hypoxia is absent with NOS inhibition.

Animals↗
PubMed1996

The effect of halothane on phrenic and chemoreceptor responses to hypoxia in anesthetized kittens.

We examined the effect of halothane on phrenic never and carotid sinus discharge during hypoxia in anesthetized kittens. In 12 animals, phrenic amplitude was measured during normoxia, during isocapnic hypoxia, and after a return to normoxia, both with and without halothane. Without halothane, all animals had an increase in phrenic amplitude during hypoxia. With halothane, half the animals showed an increase in phrenic amplitude followed by a decline. In a second group of animals, recordings were obtained from single or a few fiber strands of carotid sinus nerve. Without halothane, an increase in chemoreceptor discharge frequency during hypoxia was seen. With 1.0% halothane, frequency was decreased during normoxia and did not increase during hypoxia. Thus, halothane's effect on the ventilatory response to hypoxia, as measured by phrenic discharge, is at least partially explained by an effect on peripheral chemoreceptors.

Action Potentials↗
PubMed1996

Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep.

Severe birth asphyxia leads to a transient organic aciduria and increased hypoxanthine excretion. To investigate its origin and timing, we analyzed urine from 12 late gestation fetal sheep in utero subjected to moderately severe isocapnic hypoxia for 1 h. In six fetuses the carotid sinus nerves were cut to determine whether reflex peripheral vasoconstriction contributed to the changes in excretion. After a control period of 1 h, maternal inspired oxygen was reduced for 1 h so that fetal arterial oxygen tension fell significantly from 2.86 +/- 0.12 kPa (mean +/- SEM) to 1.55 +/- 0.04 kPa. The ewes were returned to normoxia, and monitoring was continued for 1 h. Fetal heart rate, arterial blood pressure, and femoral arterial blood flow (intact fetuses only) were recorded, and arterial pH, blood gases, and lactate were measured. Urine collected via a bladder catheter was analyzed for organic acids and hypoxanthine with gas chromatography-mass spectrometry. In intact fetuses, hypoxia increased excretion of hypoxanthine and several organic acids, notably lactic acid and intermediates of valine catabolism. Changes were apparent by 15 min, significant by 45 min, and maximal after reoxygenation. In denervated fetuses, there were small, significant, increases in organic acids and hypoxanthine by 45 min of hypoxia, but there was no surge in excretion posthypoxia. Hypoxia caused a large, significant, fall in femoral arterial blood flow in intact fetuses. We conclude that the extent of the reflex peripheral vasoconstriction, particularly in skeletal muscle, determines the amount of organic acid and hypoxanthine excretion and may explain similar biochemical disturbances after birth asphyxia. Urinary lactic acid measurement has a potential value for grading birth asphyxia.

Animals↗
PubMed1995

The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats.

1. Reports that maternal anaemia in pregnancy is associated with a greater placental: birth weight ratio, which predisposes towards high postnatal blood pressure in the human, led us to examine the effects of maternal anaemia during pregnancy on placental size, fetal and neonatal growth, and blood pressure development in the rat. 2. Nutritional anaemia was induced in female rats prior to mating and maintained throughout pregnancy and up until weaning of the pups. Fetuses were studied at 20 days of gestation (E20). Pups were studied on postnatal days 20 (P20) and 40 (P40), having been weaned onto normal rat chow at 21 days. 3. In the anaemic group placental: fetal body weight ratios were lower compared with controls. Body weights at all ages were lower in the anaemic group than in controls, despite a greater rate of growth in the anaemic group between P20 and P40. 4. At P20 heart weights of the anaemic group were almost twice that of controls, suggesting an alteration in their cardiovascular development. However, paradoxically, the systolic blood pressure of the anaemic group was lower than that of controls. 5. By P40 the systolic blood pressure of the anaemic group (136 +/- 3 mmHg) had increased and was greater than that in control pups (126 +/- 3 mmHg). 6. In conclusion, we have shown that there is a pronounced postnatal rise in systolic blood pressure associated with maternal anaemia during pregnancy, which is not related to a greater placental: birth weight ratio. Before weaning, anaemic pups have a lower systolic blood pressure than controls and there is an important association between the rate of postnatal growth and blood pressure.

Anemia↗
PubMed1995

Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero.

1. We studied the effects of systemic administration of the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor antagonist prazosin on fetal breathing movements (FBM) and electrocortical activity (ECoG) in fetal sheep. In one group of fetuses (group I; n = 7) the effects of phentolamine were measured during normoxia and hypoxia. In the second group of fetuses (group II; n = 8) the effects of either phentolamine, or combined phentolamine and prazosin, or prazosin alone, were measured during normoxia. 2. In group I fetuses, the incidence of FBM increased after phentolamine treatment. An increase in the incidence and mean episode duration of low-voltage ECoG (LV-ECoG) was also measured after phentolamine treatment. These effects of phentolamine persisted during hypoxia. 3. In group II fetuses a pronounced decrease in the incidence of FBM occurred after administration of prazosin following either phentolamine or saline pretreatment. These effects of prazosin on FBM were independent of an effect on ECoG activity. 4. We conclude that catecholamines have a stimulatory role on FBM mediated via an alpha 1-adrenoreceptor mechanism. Phentolamine leads to an increase in FBM by preferentially antagonizing presynaptic alpha 2-adrenoreceptors over postsynaptic alpha 1-adrenoreceptors. This influence of phentolamine on FBM may be secondary to its effect on ECoG. Promotion of LV-ECoG by catecholamines is mediated via an alpha 1-independent mechanism.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Blood pressure and cardiovascular reflex development in fetal sheep. Relation to hypoxaemia, weight, and blood glucose.

We measured mean arterial blood pressure (MAP), fetal heart rate (FHR), the baroreflex, weight, blood gases, blood glucose and lactate in chronically instrumented fetal sheep for 14 days from Day 105 to Day 109 gestation, with or without daily administration of 1 h of acute isocapnic hypoxaemia (arterial O2 partial pressure, PaO2, 11-13 mm Hg; 1 mm Hg = 133 Pa). Fetuses subjected to hypoxia showed no significant differences in MAP or FHR v. control fetuses. However, examination of all fetuses together revealed that there were two distinct groups: those showing a rise in MAP over the 14 days ('pressure up' group, PU), and those in which blood pressure did not increase or showed only a slight decrease ('pressure down' group, PD). PU fetuses were proportionately larger than PD fetuses. In contrast to PU fetuses, PD fetuses had lower blood glucose concentration, arterial O2 saturation (SaO2), PaO2, total haemoglobin, haematocrit and oxygen content, and higher lactate concentration, pH and PaCO2. PU fetuses showed a shift of the baroreflex MAP/R-R interval curve to the right, however, the PD group showed a shift upwards from Day 1 to Day 14. The PD group responded to hypoxia with a greater increase in MAP than the PU group. Thus, repeated acute moderate isocapnic hypoxia does not affect development of MAP or FHR in late gestation fetal sheep. However, MAP follows different trajectories in individual fetuses, related to fetal size and the availability of oxygen and/or glucose. Cardiovascular chemoreflexes and baroreflexes are also different, depending on the MAP trajectory. These data indicate an important association between growth and blood pressure development, and also show that differences in growth are associated with changes in cardiovascular control.

Animals↗
PubMed1994

Carotid sinus nerve section and the increase in plasma cortisol during acute hypoxia in fetal sheep.

1. We studied the effects of acute isocapnic hypoxia on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in sixteen sheep fetuses at 118-125 days of gestation (term is 147 days). Eight fetuses had their carotid sinus nerves cut (denervation); the remaining eight had these nerves left intact. 2. There were no differences in the plasma concentrations of ACTH or cortisol between intact and denervated fetuses during normoxia. 3. Whilst plasma cortisol increased in early (after 15 min) and late (after 45 min) hypoxia in intact fetuses, the rise in cortisol in denervated fetuses was delayed, increasing significantly only by late hypoxia. 4. In contrast, plasma ACTH concentrations were increased in early and late hypoxia in both intact and denervated fetuses. The rise was smaller in denervated fetuses, but was not significantly different from that in intact fetuses. 5. Our results indicate that, in the sheep fetus, carotid sinus nerve section delays the rise in plasma cortisol in response to acute hypoxia without affecting the ACTH response. Further work is needed to establish the mechanism underlying this effect of denervation.

Acute Disease↗
PubMed1994

Effect of carotid denervation on plasma vasopressin levels during acute hypoxia in the late-gestation sheep fetus.

1. We measured plasma concentrations of arginine vasopressin (AVP), arterial, venous and amniotic pressures, and carotid and femoral blood flows in fifteen chronically instrumented fetal sheep at 119-125 days of gestation. In eight of the fetuses the carotid sinus nerves were cut (denervated fetuses); the other seven remained intact and served as controls (intact fetuses). 2. In the intact fetuses during hypoxia there was an increase in plasma [AVP] and in perfusion (arterial-venous) pressure, a transient bradycardia, and an increase in carotid and a decrease in femoral blood flow. Whilst femoral vascular resistance (perfusion pressure/femoral blood flow) increased, there were no changes in carotid vascular resistance during hypoxia. 3. In the denervated fetuses no significant bradycardia, fall in femoral blood flow or increase in femoral vascular resistance was present soon after the onset of hypoxia but plasma AVP increased to similar concentrations to those observed in intact fetuses during hypoxia. 4. We conclude that carotid denervation does not affect plasma [AVP] during hypoxia in fetal sheep. This suggests that (1) AVP release during hypoxia is not mediated by a carotid chemoreflex and (2) AVP does not play an important role in these initial fetal cardiovascular responses. Furthermore, we previously reported that intact fetuses survive acute hypoxia better than denervated fetuses following phentolamine treatment, and we believe this to be due to the action of a non-alpha-adrenergic vasoconstrictor released in part via a carotid chemoreflex. The present results suggest that this vasoconstrictor is not AVP.

Acute Disease↗
PubMed1993

Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep.

1. We studied the effects of acute isocapnic hypoxia on arterial and central venous pressures, carotid and femoral blood flows and heart rate in intact and carotid denervated fetal sheep between 118 and 125 days gestation, after pre-treatment with either saline, atropine or phentolamine. Electrocortical activity (ECoG) and the incidence of fetal breathing movements (FBM) were also compared between intact and carotid denervated fetuses. 2. There were no significant differences between intact and denervated fetuses in any variable measured during normoxia. Soon after the onset of hypoxia a marked bradycardia occurred in intact, but not in denervated fetuses. Femoral blood flow and femoral vascular resistance (perfusion pressure/femoral blood flow) increased in intact, but not in denervated fetuses. Carotid blood flow increased in both groups of fetuses during hypoxia, but carotid vascular resistance did not change. During hypoxia, the incidence of FBM and low-voltage ECoG was similarly reduced in both groups of fetuses. 3. Atropine produced a rise in fetal heart rate during the control period in intact but not in denervated fetuses. At the onset of hypoxia atropine prevented the initial bradycardia seen in intact fetuses. In denervated fetuses a further increase in heart rate occurred throughout the hypoxia. 4. All denervated fetuses treated with phentolamine died during the hypoxic challenge, but nine out of fourteen intact fetuses treated with phentolamine survived. 5. In intact fetuses which survived hypoxia after treatment with phentolamine, the increase in arterial blood pressure was smaller and the increase in femoral resistance did not occur. In these fetuses a rise in heart rate occurred in hypoxia. Carotid vascular resistance decreased during hypoxia after administration of phentolamine. 6. Our results indicate that the initial cardiovascular responses of the late gestation sheep fetus to hypoxia are reflex, and that the carotid chemoreceptors provide the afferent limb of this reflex. The bradycardia is mediated through a muscarinic pathway, as it is blocked by atropine. The femoral vasoconstriction is mediated through an alpha-adrenergic mechanism, mediated both neurally by a carotid chemoreflex and via catecholamines released directly from the adrenal medulla. Both these components are blocked by phentolamine. 7. The differences in survival between intact and denervated fetuses during hypoxia after phentolamine suggest that the carotid chemoreflex response to hypoxia involves mechanisms in addition to vagal efferents to the heart and alpha-adrenergic actions at peripheral blood vessels.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1990

The effects of corticotrophin-releasing factor and two antagonists on breathing movements in fetal sheep.

1. The respiratory effects of corticotrophin-releasing factor (CRF) and the CRF antagonists alpha-helical CRF 9-41 (alpha hCRF) and [DPhe 12, Nle 21-38] rCRF (12-41) (DPhe CRF) have been studied in unanaesthetized fetal lambs of 125-140 days gestation. 2. CRF when given as a 10 micrograms bolus followed by a 5 micrograms h-1 infusion into a lateral cerebral ventricle caused prolonged continuous fetal breathing movements which were stimulated in both amplitude and frequency but which did not persist during hypoxia. 3. Lower doses of CRF (20 ng bolus followed by 10 ng h-1) increased the amplitude but not the frequency of fetal breathing movements which did not become continuous. 4. At higher doses (20 micrograms bolus followed by 10-15 micrograms h-1) CRF induced cerebral convulsions which were also associated with fetal breathing movements of increased amplitude and frequency. 5. The CRF antagonists alpha hCRF and DPhe CRF both inhibited fetal breathing movements and induced a prolonged apnoea which was resistant to the stimulatory effects of 5-6% hypercapnia. 6. We conclude that CRF stimulates breathing movements in the fetal lamb. The finding that administration of the CRF antagonists alone cause apnoea suggests that CRF may have a tonic role in the regulation of fetal breathing movements.

Action Potentials↗
PubMed1990

Almitrine mimics hypoxia in fetal sheep with lateral pontine lesions.

Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species. It acts by stimulating the peripheral chemoreceptors, where it has been shown to accumulate specifically, although its exact mechanism of action is uncertain. In the fetal lamb, however, it produces a profound inhibition of breathing even after denervation of the peripheral chemoreceptors. In this respect its action is similar to hypoxia. To investigate whether almitrine is hypoxia mimetic, we examined the effect of almitrine in nine fetal lambs of 120-130 days gestation. Five had lesions in the lateral pons that changed the fetal depressive response to hypoxia to one of stimulation. In the remaining four fetuses, the lesions did not bilaterally encompass the appropriate area of the pons; thus they still showed the normal fetal depressive response to hypoxia and so acted as controls. Almitrine (10 mg iv) caused a pronounced stimulation of breathing that lasted 406 +/- 26 min in all five fetuses with lesions that caused a stimulatory response to hypoxia. However, in the remaining four fetuses, in which the response to hypoxia was inhibitory, almitrine caused an inhibition of breathing that lasted 184 +/- 28 min. We conclude that the action of almitrine is like that of hypoxia and that, because it acts specifically on the chemoreceptors, it may prove to be a useful tool in the study of possible central chemoreceptor mechanisms.

Almitrine↗
PubMed1990

Apneic effects of cholecystokinin in unanaesthetized fetal sheep.

The effects on breathing movements and sleep state of cholecystokinin octapeptide (CCK-8) and its antagonist, proglumide, have been studied in unanaesthetised fetal lambs of 124-142 days gestation. CCK-8 when given into a lateral cerebral ventricle as bolus injections of 10-500 ng caused dose-related periods of apnea ranging from 63-214 min. When given as a 100 ng bolus followed by a 50 ng/h infusion for 2 h there was a prolonged period of apnea lasting 331 +/- 56 min. There was no effect of CCK-8 when given in higher doses (1-50 micrograms). The antagonist proglumide reversed the apnea induced by CCK-8 infusion, but had no effect when given alone, nor did it affect the normal fetal depressive response to hypoxia. Neither CCK-8 nor proglumide had any effect on electrocortical activity. We conclude that CCK has no role in the inhibitory mechanisms causing the apnea associated with high voltage electrocortical activity or hypoxia in the fetus. Furthermore CCK does not appear to be involved in the regulation of sleep state in the fetal lamb.

Animals↗
PubMed1989

Presence of a diurnal rhythm in fetal prolactin secretion and influence of maternal nutrition.

The possible effect of altered maternal nutrition on fetal prolactin (PRL) secretion and the possible presence of a diurnal rhythm in fetal PRL secretion has been investigated in 11 fetuses aged between 132 and 140 days of gestation. Fetal PRL levels in 4 of 5 ewes fed once a day were high (greater than 40 ng/ml) and exhibited a distinct diurnal rhythm in PRL secretion. Fetal PRL levels in those fetuses where ewes fed 4-hourly (n = 6) were all low (less than 10 ng/ml) and did not exhibit a diurnal rhythm. This study suggests that frequent maternal feeding results in low fetal PRL concentrations and that maternal undernutrition results in high fetal PRL levels that exhibit a distinct diurnal rhythm.

Animals↗
PubMed1989

The neuroprotective actions of a calcium channel antagonist, flunarizine, in the infant rat.

One postulated final common pathway leading to neuronal death after hypoxic-ischemic insults is an increase in intracellular calcium concentrations. We examined the effect of pretreatment with flunarizine, a calcium channel antagonist known to pass the blood brain barrier, on the behavioral and histologic changes after an hypoxic-ischemic insult in the infant rat. The 21-d-old rats were subjected to unilateral carotid ligation, then to 2 h of hypoxia. They were pretreated with either flunarizine (30 mg/kg, intraperitoneally) or with an equal volume of diluent. After 5 days of observation they were killed for histology. Acute behavioral abnormalities were observed in more controls than treatment animals, 52 vs 11% (p less than 0.002). Cerebral injury was almost entirely confined to the ligated side and was significantly worse in the control rats. Full thickness cortical infarction was noted in 56% of controls (n = 27) vs 4% of flunarizine-treated rats (n = 24), (p less than 0.001). Mean and maximum damage scores for all areas assessed including cortex, corpus striatum, thalamus, amygdala, and hippocampus were improved markedly in treatment rats (p less than 0.005). These observations confirm that flunarizine, when given prophylactically, has a neuroprotective effect against hypoxic-ischemic injury in the developing brain.

Animals↗