Search PubMed⌕ Search

Biomedical subjects

J Seylaz

Publications and source records attributed to J Seylaz.

At least 163 records · Page 9Linked to original sources

Relaxation by dopaminergic agonists in cerebral and peripheral arteries (in vitro).

The receptors involved in dopamine-induced relaxation were investigated in whole segments of rabbit middle cerebral (M.C.A.) and central ear arteries (C.E.A.) by measuring pressure changes in a constant-flow in vitro set-up. Drug administrations were made in the perfusate. During treatment with high-K+ solution to induce active contraction, and in the presence of 3 x 10(-5) M phenoxybenzamine to prevent alpha-adrenergic contractions, cumulative concentration-response curves were obtained for dopamine, apomorphine, bromocriptine and piribedil. The effects of the dopamine receptor antagonists, sulpiride, haloperidol and droperidol, and a beta-adrenergic antagonist, propranolol, were tested on the concentration-response curves obtained with dopamine. The results can be summarized as follows: the dopaminergic agonists had a relaxant effect in 50% of C.E.A. and in 70% of M.C.A. after alpha-adrenergic receptor blockade. This effect was blocked by the 3 antagonists in the M.C.A., and this antagonism appeared to be competitive in the case of sulpiride. In the C.E.A., haloperidol and droperidol exerted complex effects on the dopamine relaxation, and sulpiride had inconsistent effects. Propranolol reduced the concentration-dependent relaxation in the C.E.A., but did not modify the relaxant effect of dopamine in the M.C.A. The present results are consistent with the hypothesis that dopaminergic agonists relax cerebral arteries by acting on specific receptors. The relaxant action on the C.E.A. seems more complex and may occur partly via beta-adrenergic receptors.

Animals↗

Validity of cerebral blood flow measurements obtained with quantitative tracer techniques.

A great number of results for the cerebral blood flow obtained in the animal with quantitative tracer techniques have been collected from the literature. They are exposed in order to compare both normal flow values in different laboratory species, and the characteristics, accuracy and sensitivity of each technique. A dramatic overall dispersion of flow values is observed, allowing neither the flow level particular to each species to be estimated, nor the average value provided by a given technique to be found. The physiological and technological causes of such a dispersion are discussed. Several techniques seem to have limitations which even alter the interpretation of their results, and especially the origin of the local or regional blood flow results. Other techniques may be criticized from the quantitative standpoint, but give more reliable results.

Anesthesia, General↗

Parasympathomimetic influence of carbachol on local cerebral blood flow in the rabbit by a direct vasodilator action and an inhibition of the sympathetic-mediated vasoconstriction.

1 Two sorts of effect of carbachol on local cerebral blood flow (caudate nucleus) have been studied: (a) a direct action on the arterial smooth muscle; (b) an interaction with the adrenergic (sympathetic) constrictor system which innervates the vascular system of this nucleus. 2 Continuous measurements of the following variables were performed in lightly anaesthetized rabbits: local blood flow (caudate nucleus), arterial blood pressure, PaO2, PaCO2. 3 After blockade of the nicotinic synapses in the superior cervical sympathetic ganglion by local hexamethonium injection, carbachol was infused into the common carotid artery, thus minimizing systemic effects of this drug. Infusions of 0.6, 1.3 and 2.5 micrograms kg-1 min-1 induced mean increases in caudate blood flow of about 8, 17 and 37% respectively, without notable modifications of other variables measured. 4 The dilator effect of 2.5 micrograms kg-1 min-1 carbachol was reduced to a mean of 12% after intravenous injection of 0.5 mg/kg atropine, and could be totally abolished by higher doses (1 to 1.5 mg/kg). 5 Administration of 2.5 micrograms kg-1 min-1 of carbachol diminished by more than 50% the reduction in caudate blood flow induced by postganglionic stimulation of the cervical sympathetic chain, but did not affect the reduction of flow obtained by intravenous infusion of noradrenaline (2.5 to 5.0 micrograms kg-1 min-1). This inhibition of the adrenergic (sympathetic) system by carbachol was not modified by high doses of atropine (1 mg/kg i.v.). 6 We conclude that: (a) the local cerebral blood flow of a deep structure can be significantly modified by activation of vascular muscarinic receptors; (b) activation of non-muscarinic prejunctional cholinoceptors can cause inhibition of the sympathetic fibres innervating the vascular bed of the same structure.

Animals↗

Multiregional cerebral blood flow changes induced by a cholinomimetic drug.

The effect of parasympathomimetic drug, carbachol, on regional cerebral blood flow was tested in the rabbit with the 14C-ethanol tissue sampling technique. Intracarotid injection of carbachol significantly increased flow with respect to untreated control animals in 6 out of 10 structures sampled. However, compared with animals to which atropine was also administered, the flow increases were greater with carbachol alone. These effects are discussed in terms of muscarinic and nicotinic activation.

Animals↗

Is there an active mechanism limiting the influence of the sympathetic system on the cerebral vascular bed? Evidence for vasomotor escape from sympathetic stimulation in the rabbit.

The influence of the cervical sympathetic chain on cerebral circulation in the rabbit was studied by means of 3 complementary techniques. Two dynamic techniques involving chronically implanted probes were used: blood flow in the caudate nucleus (CN) was measured by thermal clearance; tissue PO2 and PCO2 in the same structure were measured by mass spectrometry. Other variables measured continuously and simultaneously included arterial blood pressure (BP), PaO2 and PaCO2. The third technique was a tissue sampling method based on the Fick principle and using 14C1 ethanol as tracer. Blood flow in 7 regions was measured at stable BP, PaO2 and PaCO2. Stimulation of the sympathetic chain at 15 Hz induced mean maximal decreases in CN blood flow of 23.9% (thermal clearance) and 24.4% (ethanol technique). Mean decrease of PO2 in the CN at 15 Hz was 16.6%. Significant falls in blood flow were observed with the ethanol technique in all 7 structures measured. During prolonged stimulation (greater than 1 min) CN blood flow and PO2 were found to escape towards the baseline level, which was sometimes even exceeded during the stimulation (blood flow). Stimulation frequency had only a very moderate influence on the rate of escape, and no evidence of a metabolic mechanism was found, although injection of barbiturate decreased the escape. These results are discussed with respect to the conflicting evidence on the effects of sympathetic stimulation in the brain, and to possible mechanisms for the escape phenomenon.

Anesthesia, General↗

The cholinergic pathway to cerebral blood vessels. II. Physiological studies.

The effect of stimulating the greater superficial petrosal nerve (g.s.p.n.) upon retroglenoid venous blood flow has been tested in anaesthetized, paralysed and artificially ventilated rats. In 11 out of 15 tests, blood flow increased by an average of 25% with a time to peak response of 28 s. This response was abolished with the injection of atropine 0.1 mg kg-1 injected intra-arterially. With both petrosal nerves intact, the administration of 6-7% CO2 in air or 15% O2 in N2 caused average increases in blood flow of 105% and 45% respectively. These responses were not affected by bilateral section of the g.s.p.n. Similar experiments were carried out in 5 anaesthetized, spontaneously breathing rabbits in which, in addition to PaCO2 and PaO2, PO2, PCO2 and blood flow in the caudate nucleus were measured continuously using chronically implanted mass spectrometer catheters and heated thermistors. Caudate nucleus blood flow increased in response to hypoxia and hypercapnia and this response was not significantly affected by section of one or both g.s.p.n., sinus or vagus nerves. With section of sinus and vagus nerves, blood flow changed passively with arterial pressure.

Animals↗

Measurement of regional cerebral blood flow by intravenous injection of Xe133.

Clearance of Xenon 133 following intravenous injection has been used to perform atraumatic measurements of regional cerebral blood flow (rCBF). rCBF was computed by a two-compartmental analysis of the clearance curves associated with a correction for Xenon recirculation based on the end-tidal tracer concentration. Direct comparison was made between the results of this method and those obtained from the reference intracarotid method. A systematic analysis has shown that the results of the non-invasive method depend on the part of the clearance curves chosen for computation of rCBF. The best concordance with the intra-carotid method was found when the analysed part of the curve was situated between 3 and 11 min. after the beginning of the injection. Under these conditions, the differences between the results from the two methods did not exceed 10% of the flow values even for low flows. Such precision makes the atraumatic measurements of rCBF by intravenous injection of Xenon valuable for clinical applications.

Cerebrovascular Circulation↗

Quantitative changes in regional cerebral blood flow of rats induced by alpha- and beta-adrenergic stimulants.

Cerebral blood flow was measured with the 14C-ethanol technique in 8 regions (frontal, parieto-temporal and occipital cortex, caudate nucleus, thalamus, cerebellum, mesencephalon, and pons) of rats. The highest flow values (83-89.5 ml/100 g/min) were found in cortical areas, whereas pons had the lowest flow (48 ml/100 g/min). Intravenous infusion of noradrenaline or adrenaline markedly reduced rCBF (by 22-48% of control levels) in all regions except thalamus, mesencephalon, and pons. The noradrenaline-induced reduction was blocked, and the effect of adrenaline reversed, after pretreatment with the alpha-receptor antagonist, phentolamine. Isoprenaline infusion markedly augmented rCBF in thalamus, mesencephalon, pons, and also in the caudate nucleus. The response was reduced by the beta-receptor antagonist, propranolol. The experiments show the presence and heterogenous distribution in the cerebrovascular bed of slpha- and beta-adrenoceptors that can be activated by sympathomimetics given systematically. If noradrenaline was allowed to pass the blood-brain barrier after osmotic opening with urea, an increased regional flow was obtained, probably due to a mechanism where the vasodilator effect secondary to activation of cerebral metabolism predominated over the direct vasoconstrictor effect of the amine.

Adrenergic alpha-Agonists↗

Intracerebral gas partial pressure changes under vasoactive drugs. A mass spectrometry study.

An original technique based on mass spectrometry has been used to measure simultaneously in undrugged, freely-breathing animals local PO2 and PCO2 in the brain (caudate nucleus) and arterial PO2 and PCO2 in the aorta. Injection of vasoactive drugs brought about significant modifications of the partial pressures of the physiological gases in the brain. The origin of these variations was discussed, based on the combination of 3 possible factors: cerebral vascular changes, systemic metabolic changes (PaO2 and PaCO2) and local metabolic changes. It was demonstrated that local variations of PCO2 cannot be held to be responsible for the modifications of cerebral blood flow induced by papaverine or the sympathomimetic drugs.

Animals↗

Continuous measurement of gas partial pressures in intracerebral tissue.

A mass spectrograph technique has been developed for measurement of physiological gas partial pressures locally in the brain. The sampling cannula is implanted stereotaxically and remains in situ for several weeks. It is a thin cylinder in shape, and is covered with a thin polyethylene membrane across which gas molecules can be sampled continuously. The conductance of this membrane is well adapted to the limited rate of replacement of gas molecules afforded by the cerebral tissue, hence there is no depletion around the cannula; this depletion has until now been the major problem of this technology. The present technique provides a continuous measurement with fast response time, which is directly proportional to the partial pressures of the gases. The variations can be expressed as a percentage of the base-line value.

Animals↗

[Action of vaso-active drugs on gasz of cerebral tissue. Experimental study by mass spectrometry (author's transl)].

The authors describe a method for measuring cerebral tissue respiration by mass spectrometry. The first applications concern the action of vaso-active drugs on intracerebral PCO2 and PO2. The information gained with this method may prove of value in elucidating the mechanisms of drug action and the regulatory mechanisms of cerebral blood flow. Further prospects of experimentation offered by the method are mentioned.

Animals↗

Radiation scattering and the determination of regional cerebral blood flow by radioisotope clearance.

The sources of error involved in the measurement of regional cerebral blood flow (rCBF) with radioactive tracers in man have been studied. This report shows that one of the main sources is the weakness of the energy emitted by the tracers used. Clearance curves obtained with scalp detectors are subject to interference: the radiation measured originates not only in the region studied but also, by scattering, from the rest of the brain. Because of the weak energy levels involved, the scattered radiation contributes significantly to the total measured radiation, and for the same reason it is impossible to distinguish clearly the scattered radiation from that arriving directly. These systematic errors in rCBF measurements were studied quantitatively by in vitro tests and computer simulation, and limits were established for resulting alterations of all varialbes determined (grey and white matter flow, mean flow, compartment weight). It was concluded that the biologic origin of a modification of rCBF can be affirmed only in the case of changes of at least 10%.

Cerebrovascular Circulation↗

Quantitative multiregional blood flow measurements during cervical sympathetic stimulation.

The ethanol tissue sampling method for rCBF measurement was used to obtain information on the effects of cervical sympathetic stimulation in 8 cerebral structures in the non-anaesthetized rabbit. Sympathetic stimulation induced flow decreases of 12-29% according to structure, confirming the capability of this nerve to significantly reduce rCBF. Furthermore, a regional differentiation of cerebral structures into an 'anterior' group (mean decrease 22%) and a 'posterior' group (mean decrease 12%) with different reactivity to stimulation was established, thus confirming previous work in this laboratory with a local thermoclearance technique, and histochemical studies on sympathetic innervation to cerebral arteries and arterioles. These results provide strong evidence of the functional nature of the sympathetic nervous system in CBF regulation. The complementary nature of the ethanol technique (quantitative, multiregional measurement) and the local thermoclearance technique (continuous, semiquantitative measurements in 2-3 regions), and the absence of anaesthesia and significant trauma, means that combination of these two techniques offers considerable advantages in research on dynamic phenomena of the kind studied here.

Anesthesia↗