Effect of ketamine on hypoxic-ischemic brain damage in newborn rats.

The present study tests the hypothesis that ketamine, a dissociative anesthetic known to be a non-competitive antagonist of the NMDA receptor, will attenuate hypoxic-ischemic damage in neonatal rat brain. Studies were performed in 7-day-old rat pups which were divided into four groups. Animals of the first group, neither ligated nor exposed to hypoxia, served as controls. The second group was exposed to hypoxic-ischemic conditions and sacrificed immediately afterwards. Animals of the third and fourth groups were treated either with saline or ketamine (20 mg/kg, i.p.) in four doses following hypoxia. Hypoxic-ischemic injury to the left cerebral hemisphere was induced by ligation of the left common carotid artery followed by 1 h of hypoxia with 8% oxygen. Measurements of high energy phosphates (ATP and phosphocreatine) and amino acids (glutamate and glutamine) and neuropathological evaluation of the hippocampal formation were used to assess the effects of hypoxia-ischemia. The combination of common carotid artery ligation and exposure to an hypoxic environment caused major alterations in the ipsilateral hemisphere. In contrast, minor alterations in amino acid concentrations were observed after the end of hypoxia in the contralateral hemisphere. These alterations were restored during the early recovery period. Post-treatment with ketamine was associated with partial restoration of energy stores and amino acid content of the left cerebral hemisphere. Limited attenuation of the damage to the hippocampal formation as demonstrated by a reduction in the number of damaged neurons was also observed. These findings demonstrate that systemically administered ketamine after hypoxia offers partial protection to the newborn rat brain against hypoxic-ischemic injury.

Recovery, innervation profile, and contractile properties of reinnervating fast muscles following postnatal nerve crush and administration of L-Dopa.

Muscle and peripheral nerve development is clearly dependent on their interaction during early postnatal life. Furthermore, muscle or peripheral nerve activity plays a crucial role in the maturation of the neuromuscular system. In this study, the possible involvement of spinal catecholamines in fast muscle recovery after nerve crush is investigated. Sciatic nerve crush was performed on the fourth to fifth postnatal day. Following that, L-Dopa was administered daily [150 mg/kg body weight (BW)] i.p., until the 21st day after birth. L-Dopa-treated and control groups were then examined electrophysiologically for the contractile properties of extensor digitorum longus (EDL) muscles. Two experimental groups were included in this study: (i) rats whose sciatic nerve was crushed and were treated with L-Dopa and (ii) rats whose sciatic nerve was crushed and were not treated with L-Dopa. The number of motoneurones for both groups was estimated by HRP retrograde labelling. The results showed that the operated L-Dopa-treated EDL muscles of the rats exhibited limited atrophy, slighter impairment of maximal tetanic tension, lesser resistance to fatigue, and polyneuronal innervation than the controls. The number of motoneurones was the same for the operated muscles in both groups of animals and was within the normal ranges. Our findings suggest that catecholamines of locomotion during the early stages of development may have a beneficial effect on fast muscle recovery following nerve crush. The action of L-Dopa is attributed to noradrenaline, which acts through descending spinal noradrenergic pathways, possibly via a(2)-adrenergic receptors at the spinal level.

Ontogenetic development of the locomotor response to levodopa in the rat.

Administration of exogenous levedopa triggers locomotion in young rats prior to the onset of quadripedal movement. The same substance decreases locomotion in adult animals. The ontogenetic development of the response to levodopa was investigated in rats. Intraperitoneal injection of levodopa (150 micrograms/kg body weight) caused characteristic "crawling" or "swimming-like" locomotion patterns in 5- to 6-day-old animals. Noradrenergic mechanisms may be involved in this behavior. In 18- to 20-day-old rats, levodopa caused excessive locomotor activity, including running, jumping, and wall climbing. This effect can be attributed to the activation of postsynaptic dopaminergic receptors that are already present during the early stages of life. At 25-30 days of age, levodopa-induced motor activity was decreased in comparison with that of the 18- to 20-day-old rats, possibly due to changing patterns of D1/D2-dopamine receptor subtype interactions. In contrast to observations in younger rats, the same dose of levodopa suppressed motor activity in 60- to 75-day-old rats. The presence of functional dopamine autoreceptors at this age may account for the change.

beta-Endorphin plasma levels after intravenous administration of GnRH in female rats.

OBJECTIVE: The study investigates the effects of intravenously administered GnRH on plasma beta-endorphin levels in female proestrous rats. STUDY DESIGN: Sixteen adult female proestrous Wistar rats, 220-250 g, were implanted with two indwelling catheters, one intracarotid and one intrajugular. Ten ng GnRH/100 microl distilled water or 100 microl saline (control) were infused in eight animals per group every 20 min from 12:30 to 14:30 h. Blood was withdrawn through the intracarotid catheter just before the initial infusion (12:30 h) and at 14:00, 15:30, 16:30 and 17:30 h for the determination of plasma beta-endorphin levels. The Mann-Whitney test was used for comparison between GnRH-treated and control rats and the Wilcoxon test within each treatment group. RESULTS: beta-Endorphin levels of GnRH-treated rats were not significantly different at any sampling moment neither compared to preinfusion time nor to the corresponding controls. CONCLUSIONS: Intravenously administered GnRH was not sufficient for any possible effect on the secretion of beta-endorphin from rat pituitary and further investigation is needed to demonstrate if a different experimental model would have any significant effect.

High altitude cognitive performance and COPD interaction.

INTRODUCTION: Thousands of people work and perform everyday in high altitude environment, either as pilots, or shift workers, or mountaineers.The problem is that most of the accidents in this environment have been attributed to human error. The objective of this study was to assess complex cognitive performance as it interacts with respiratory insufficiency at altitudes of 8000 feet and identify the potential effect of hypoxia on safe performance. METHODS: Twenty subjects participated in the study, divided in two groups: Group I with mild asymptomatic chronic obstructive pulmonary disease (COPD), and Group II with normal respiratory function. Altitude was simulated at 8000 ft. using gas mixtures. RESULTS: Individuals with mild COPD experienced notable hypoxemia with significant performance decrements and increased number of errors at cabin altitude, compared to normal subjects, whereas their blood pressure significantly increased.

Intracerebroventricular administration of atrial natriuretic peptide prevents increase of plasma ADH, aldosterone and corticosterone levels in restrained conscious dehydrated rabbits.

In order to investigate the effects of centrally administered ANP on plasma ADH, aldosterone and corticosterone levels as well as on blood pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used. Measurements were made on restrained conscious animals one week after the implantation of an indwelling intracerebroventricular (icv) cannula and two indwelling intravascular catheters (intracarotid and intrajugular). Animals were classified into two main groups, those with water available ad libitum ("euhydrated" group) and those who were dehydrated for 24 h ("dehydrated" group) before blood pressure and heart rate recordings and blood sampling for hormonal determination. Each group's individuals were divided into two subgroups of five animals each. Blood samples were collected at 0 min (control) and 30, 60, 90, 120 min following icv administration of 25 microl of either artificial cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microg) in aCSF (25 microl) (subgroups "hANP"). Blood pressure and heart rate were also recorded at the same times. Plasma ADH, aldosterone and corticosterone concentrations were determined using RIA. The results were analysed by analysis of variance (ANOVA). Blood pressure and heart rate values were unaffected by water deprivation or by ANP administration. Mean plasma corticosterone levels at all times (30-120 min) were significantly higher (p<0.001) than those at 0 min time. Plasma corticosterone levels in the "dehydrated+aCSF" group were significantly higher (p<0.05) than in each of the other groups ("dehydrated+hANP", "euhydrated+aCSF", "euhydrated+hANP"). Plasma corticosterone levels in each of those other groups did not differ significantly from one another. Dehydration resulted in a tendency to increase in aldosterone levels (p<0.07), and icv administration of hANP tended (p<0.08) to prevent in the "dehydrated+hANP" experimental group the increase in aldosterone levels observed in the control "dehydrated+aCSF" group from 30 to 120 min. Dehydration resulted in an increase in ADH levels (p<0.0001), and icv administration of hANP prevented (p<0.05) in "dehydrated+hANP" experimental group the increase in ADH levels observed in the control "dehydrated+aCSF" group from 90 to 120 min. The increase of corticosterone and ADH and the tendency towards increase in aldosterone in the control dehydrated groups could possibly be due to the combined stress stimulus of dehydration and restriction in the restrain box. These results indicate that centrally administered ANP, at the concentration achieved in the present study, neither affects blood pressure and heart rate in conscious restrained euhydrated and 24 h-dehydrated NZW rabbits nor decreases the ADH, aldosterone and corticosterone response to dehydration, but does apparently modulate ADH, aldosterone and corticosterone responses to other stimuli in the dehydrated state. In conclusion, the results of this study confirm that brain ANP may have an inhibitory effect on stimulated ADH, aldosterone and corticosterone release.

Histochemical and ultrastructural characteristics of leg muscle fibres in patients with repairative abdominal aortic aneurysm (AAA).

Tibialis anterior (ta) muscle biopsies before and after elective abdominal aortic aneurysm (AAA) repair operation were obtained, in order to observe possible changes after the aortic declamping reperfusion. Open muscle biopsies were taken from each of eight patients (60-75 years old) which were processed for enzyme histochemistry, and for transmission electron microscopy (EM). Morphometric analysis was applied to estimate the number and the area of muscle fibres of each fibre type. Rectus abdominis muscle biopsies were served as controls. Before the operation the predominant elements found were the presence of atrophic muscle fibres, fibre size diversity, localised cellular reactions, increased extent of connective tissue, disappearance, in many cases, of the mosaic pattern, predominance of type I and oxidative fibres, and existence of fibres with core-like structures in the sarcoplasm. Type I fibres consisted of 66.95 +/- 9% of all muscle fibres, the mean cross sectional area of which was 3,372.8 +/- 1,016 microm(2) and of type II fibres was 3,786.5 +/- 6,046 microm(2). After the aortic clamping was performed mitochondrial swelling was found, as well as disorganisation of sarcomeres. After declamping of the aorta, there were also severe edema, local fibre necrosis, and adhesion of leucocytes, whereas muscle fibre areas became 3,935.18 micro 531 microm(2) for type I and 5,804 +/- 1,075 microm(2) for type II. The short ischemic period during aortic clamping and the subsequent reperfusion resulted mainly in ultrastructural changes.

The effect of intraventricularly administered GnRH on plasma beta-endorphin levels of the rat.

This study investigates the effects of intraventricularly administered gonadotropin-releasing hormone (GnRH) on plasma beta-endorphin levels in female proestrous rats. Adult female Wistar rats (220-250 g) were implanted with an indwelling cannula in the third ventricle. Approximately 20 days later, the animals which had established a regular 4-day cycle were implanted with two indwelling catheters, one intracarotid and one intrajugular, on the morning of proestrus. A single injection of 100 ng GnRH dissolved in 5 microliters distilled water or 5 microliters of saline (control) was infused slowly through the cannula in the third ventricle. Blood was withdrawn via the intracarotid catheter just before the infusion (12.30 h) and at 14.00, 15.30, 16.30 and 17.30 h for the determination of plasma beta-endorphin levels. The results indicated that intracerebroventricular infusion of GnRH causes a significant decline of plasma beta-endorphin levels at all time points. It is postulated that GnRH possibly causes desensitization of GnRH receptors, due to the continuous GnRH supply to the pituitary via the blood circulation.

The effects of exercise training on muscle atrophy in haemodialysis patients.

BACKGROUND: Patients with end-stage renal disease on haemodialysis (HD) have limited work capacity. Many structural and functional alterations in skeletal muscles contribute to this disability. METHODS: To evaluate the effects of exercise training on uraemic myopathy, seven HD patients (mean age 44.1+/-17.2 years) were studied. Open muscle biopsies were taken from their vastus lateralis muscle before and after a 6-month exercise rehabilitation programme and examined by routine light- and transmission electron-microscopy. Histochemical stainings of frozen sections were performed and morphometric analysis was also applied to estimate the proportion of each fibre type and the muscle fibre area. Spiroergometric and neurophysiological testing and peak extension forces of the lower limbs were measured before and after exercise training. RESULTS: All patients showed impaired exercise capacity, which was associated with marked muscular atrophy (mean area 2548+/-463 microm2) and reduction in muscle strength and nerve conduction velocity. All types of fibres were atrophied, but type II were more affected. The ultrastructural study showed severe degenerative changes in skeletal muscle fibres, mitochondria, and capillaries. Exercise training had an impressive effect on muscular atrophy; in particular the proportion of type II fibres increased by 51% and mean muscle fibre area by 29%. Favourable changes were also seen on the structure and number of capillaries and mitochondria. These results were confirmed by a 48% increase in VO2 peak and a 29% in exercise time, as well as an improvement in the peak muscle strength of the lower limbs and in nerve conduction velocity. CONCLUSIONS: Skeletal muscle atrophy in HD patients contribute to their poor exercise tolerance. The application of an exercise training rehabilitation programme improved muscle atrophy markedly, and therefore had beneficial effects in overall work performance.

Effects of intracerebroventricular administration of atrial natriuretic peptide (ANP) on blood pressure, heart rate and plasma ADH and corticosterone levels in normal and dehydrated rabbits.

In order to investigate the effects of centrally administered Atrial Natriuretic Peptide (ANP) on plasma ADH and corticosterone levels as well as on blood pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used. Measurements were made on restrained conscious animals one week after the implantation of an indwelling intracerebroventricular (i.c.v.) cannula and two indwelling intravascular catheters (intracarotid and intrajugular). Animals were classified into two main groups, those with water available ad libitum ("euhydrated" group) and those who were dehydrated for 24h ("dehydrated" group) before blood pressure and heart rate recordings and blood sampling for hormonal determination. Each group's individuals were divided into two subgroups of five animals each. Blood samples were collected at 0 min (control) and 30; 60, 90, 120 min following i.c.v. administration of 25 microliters of either artificial cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microgram) in aCSF (25 microliters) (subgroups "hANP"). Blood pressure and heart rate were also recorded at the same times. Plasma ADH and corticosterone concentrations were determined by RIA. The results were analysed by ANOVA. Blood pressure and heart rate values were unaffected by water deprivation or by ANP administration. Mean plasma corticosterone levels at all times (30-120 min) were significantly higher (p < 0.001) than at 0 min time. Plasma corticosterone levels in the "dehydrated + aCSF" group were significantly higher (p < 0.05) than in each of the other groups ("dehydrated + hANP", "euhydrated + aCSF", "euhydrated + hANP"). Plasma corticosterone levels in each of those other groups did not differ significantly from one another. Dehydration resulted in an increase in ADH levels (p < 0.0001) and i.c.v. administration of hANP prevented (p < 0.05) in "dehydrated + hANP" experimental group, the increase in ADH levels observed in the control "dehydrated + aCSF" group from 90 to 120 min. The increase of corticosterone and ADH in the control dehydrated groups could possibly be due to the combined stress stimulus of dehydration and restriction in the restrain box. These results indicate that centrally administered ANP, at the concentration achieved in the present study, neither affects blood pressure and heart rate in conscious restrained euhydrated and 24h-dehydrated NZW rabbits nor decreases the ADH and corticosterone response to dehydration, but does apparently modulate ADH and corticosterone responses to other stimuli in the dehydrated state. In conclusion, the results of this study confirm that brain ANP may have an inhibitory effect on stimulated ADH and corticosterone release.