Quantified EEG analysis monitoring in a novel model of general anaesthesia in rats.

The aim of this research was to evaluate the safety and reliability of an anaesthetic mixture (Equitensine: pentobarbital, chloral hydrate, dihydroxypropane, ethanol) which, unlike other 'classic' anaesthetics, such as ketamine [The Electroencephalogram in Anaesthesia, Springer, Berlin, 1984], has been demonstrated not to induce alterations in the extracellular concentrations of cerebral excitatory amino acids. Quantified EEG analysis monitoring and behavioural observation were used to quantify the degree and the time course of the changes in cerebral electrical activity, analgesia and sedation induced, in rats, by the compound under investigation. Equitensine (0.

Ischemia-induced glutamate release in rat frontoparietal cortex after chronic alcohol and withdrawal.

High doses of ethanol increase stroke risk: in this context, a role for excitatory amino acids has been proposed. The present results show that, in frontoparietal cerebral cortex, chronic ethanol treatment (10% v/v in drinking water for 28 days) was able to slightly reduce glutamate release (evaluated through transdialysis coupled with high-pressure liquid chromatography) following focal ischemia as regards non-treated ischemic rats. This reduction was, however, not associated with decreased cerebral damage.

Acute cerebral focal ischaemia alters the adrenergic and NANC responses in the bisected rat vas deferens.

1. Disturbances of the autonomic nervous system are common in right hemisphere stroke patients, including a marked decline in male sexual functions. There is a lack of information on the influence of stroke on male secondary sex organs such as the vas deferens.

The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat.

Focal ischemia was induced in the fronto-parietal region of rat brain, by injection of Rose Bengal, followed by light activation. Focal ischemia was accompanied by formation of PGD(2) peaking 60-90 min post irradiation and declining thereafter. Increased Cycloxygenase-2 (COX-2) expression was also observed.

Effect of acute alcohol on ischemia-induced glutamate release and brain damage.

Epidemiological studies show that chronic ethanol consumption at high doses enhances the risk of cerebral stroke. The mechanisms responsible for the greater vulnerability of alcoholics' brains to stroke have to be completely understood, but a role for excitatory amino acids has been suggested. In order to study the interaction between alcohol and ischemia, we investigated the effect of acute alcohol administration in a model of focal cerebral ischemia.

Influence of different anaesthetics on extracellular aminoacids in rat brain.

We used different anaesthetic procedures to study the possible effects of anaesthesia on extracellular aminoacid concentration in rat brain. Glutamate, aspartate and glycine concentrations were determined by HPLC in samples collected from the right fronto-parietal region of the rat brain cortex by transcerebral microdialysis before and up to 2 h following anaesthesia induction. Anaesthesia induced by ketamine, alone or in association with xylazine, caused a significant decrease in the levels of glutamate, aspartate and glycine, compared to before anaesthesia values (range: 27-72% according to the time of sampling and to the anaesthetic used).

Inhibition of prostanoid synthesis protects against neuronal damage induced by focal ischemia in rat brain.

Changes in prostanoids concentration and effects of the non-specific COX inhibitor indomethacin on prostanoids levels and extension of tissue damage were studied following focal ischemia induction in the fronto-parietal region of rat brain. Ischemia was induced in animals bearing a transcerebral microdialysis probe by injection of Rose Bengal, a photosensitive dye, followed by light activation. Prostanoid levels were determined in the dialysate using immunoenzymatic techniques.

Effect of idebenone on in vivo serotonin release and serotonergic receptors in young and aged rats.

The effect of idebenone on the serotonergic system was evaluated in the aging rat by measuring the kinetic constants of 3H-5HT and 3H-ketanserin binding sites in the cerebral cortex of rats at 3, 15 and 24 months of age following acute and subchronic administration of the drug. Idebenone displayed no in vitro affinity toward any population of serotonin receptors and did not modify their kinetic parameters after a single dose of 100 mg/kg, at any age tested. A subchronic treatment with the drug for 21 days at the dose of 30 mg/kg did not induce any relevant change in 3- and 15-month-old rats, whereas it significantly increased the density of both 3H-5HT and 3H-ketanserin binding sites in 24-month-old rats, where a lower number of receptors is detected as a consequence of aging.

Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in brain cortex of rats.

A photochemical method using the Rose Bengal dye as thrombogenic agent was employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A transcerebral microdialysis probe was used to collect samples from ischemic cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within the first hour occurred.

K-opioid receptor changes in experimental models of cerebral ischaemia and atherosclerosis in the rabbit.

Thromboembolic phenomena and transient ischaemic attacks (TIA) are considered the basis of ischaemic pathologies. The aim of the present research is to investigate the involvement of k-opioid receptors in cerebral blood flow (CBF) impairment which results in experimental stroke or dietary atherosclerosis in rabbits. CBF measurement showed a significant decrease in rabbits submitted to embolization and/or atherosclerosis.

[The effect of superoxide dismutase and catalase on the delayed toxicity of doxorubicin].

The production of oxygen-free radicals has been proposed as a determinant of the delayed toxicity of doxorubicin. The aim of the present investigation was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) and catalase (CAT) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks.

[The prevention of the myocardial toxicity of doxorubicin with superoxide dismutase].

The production of oxygen free radicals during anthracycline therapy has been proposed as a determinant of the toxicity of anthracyclines. Oxygen radical generation might specifically affect the myocardium because of the low antioxidant defense systems in cardiac tissue. The aim of the present investigations was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model.

Ischemic cerebral pathologies and K opioid receptors in rabbits.

Recently it has been suggested that endogenous k-opioid receptors may have a physiopathological role in ischemia induced neurodegeneration. The aim of this research is to show that in experimental thromboembolic (obtained mechanically using microspheres injected in the carotid) and atherosclerotic pathologies (obtained through a special diet) there is a common mechanism which involves mediation by dynorphine and the receptor compartment considered. The results, obtained using receptor binding techniques, showed a statistically significant increase in the number of k-opioid receptors (Bmax) without variations in the affinity (Kd) for the 3H dynorphine.

Effect of flunarizine on the delayed cardiotoxicity of doxorubicin in rats.

The calcium antagonist flunarizine (FLN) was tested for its ability to prevent doxorubicin (DXR)-induced cardiotoxicity in the rat. A cumulative dose of 9.0 mg/kg of DXR was administered i.

Prevention of doxorubicin-induced cardiomyopathy by reduced glutathione.

The aim of the present investigation was to evaluate the potential cardioprotective effect of reduced glutathione (GSH) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a well-documented rat model. DXR was administered i.v.

Evaluation of the cardiovascular toxic effect of recombinant interleukin-2 in rats.

Cardiac and vascular toxicity of recombinant interleukin-2 (rIL-2) was evaluated by in vitro and in vivo experiments in rats. Using isolated spontaneously beating atria, no changes were detected in heart rate or myocardial contractility in response to rIL-2 treatment at concentrations ranging from 0.1-100 U/ml.

Kappa-opioid receptor changes and neurophysiological alterations during cerebral ischemia in rabbits.

Endogenous opioids have been shown to produce beneficial effects in experimental stroke. To evaluate both neurophysiological and biochemical parameters, we induced massive cerebral ischemia in 11 rabbits according to the method standardized in our laboratory, using microspheres injected through the internal carotid artery. Binding studies were performed in the 11 embolized, in nine control, and in five sham-operated rabbits using the appropriate concentration of [3H]dynorphin A (1-8).

Effect of ICRF-187 pretreatment against doxorubicin-induced delayed cardiotoxicity in the rat.

Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats.

Effect of glutathione and N-acetylcysteine on in vitro and in vivo cardiac toxicity of doxorubicin.

The effects of two sulfhydryl compounds, glutathione (GSH) and N-acetylcysteine (NAC), on the cardiotoxicity of doxorubicin (DXR) were tested on in vitro and in vivo models. DXR was administered to rats as 4 weekly i.v.

The rat model in the comparative evaluation of anthracyclines cardiotoxicity.

In the present investigation, the cardiotoxic effects of three anthracycline analogs (doxorubicin, 4'-epi-doxorubicin and 4'-deoxy-doxorubicin) were compared. For this purpose, 9.0 mg/kg of doxorubicin, divided into three closely spaced subdoses, were injected intravenously in rats.

Evaluation of cardiotoxicity of a new anthracycline derivative: 4'-deoxy-4'-iodo-doxorubicin.

The present study in rats was performed to evaluate the cardiotoxic activity of 4'-deoxy-4'-iodo-doxorubicin (4'-deoxy-4'-I-DXR), a new anthracycline derivative with interesting antineoplastic properties and possible lower cardiotoxicity than doxorubicin (DXR). DXR produced ECG alterations consisting of a progressive and irreversible prolongation of SaT and QaT. In contrast, in 4'-deoxy-4'-I-DXR-treated rats the increase in SaT and QaT duration was significantly lower than that observed in DXR-treated rats and slightly increased over controls.

Trifluoperazine does not affect doxorubicin cardiotoxicity in the rat.

Sprague Dawley rats received doxorubicin (DXR) at a dose of 3 mg/kg i.v. every third day for a total of three administrations, according to an acute and delayed cardiotoxicity experimental model previously described.

Effect of adriamycin on myocardial contractility and on the action of antibiotic ionophores.

In the isolated guinea pig atria adriamycin exerted a negative inotropic effect; calcium ionophores A23187 and X537A increased the force of contraction. In the presence of adriamycin only the positive inotropic effect of ionophore A23187 was significantly reduced. It may be deduced that adriamycin shows its negative inotropic effect by inhibiting the entry of extracellular Ca++ into the myocardial cells and the release of Ca++ from intracellular stores.