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Biomedical subjects

A J Porsius

Publications and source records attributed to A J Porsius.

At least 73 records · Page 4Linked to original sources
PubMed1981

Central effects of paraoxon on haemodynamics in the cat.

Application of paraoxon into the left vertebral artery (8--80 micrograms) or both the left and right vertebral artery (4--8 micrograms) of the anaesthetized cat evoked dose-dependent depressor effects, whereas heart rate was not influenced significantly. Also after systemic administration of paraoxon (150--825 micrograms . kg-1), while peripheral muscarinic receptors were blocked, depressor effects were still observed. Dose-response curves for the depressor response to paraoxon were established. Infusion of low doses of dexetimide via the vertebral artery prevented the hypotensive action of paraoxon. The distribution of this antimuscarinic drug in the brain was investigated. The depressor effect of paraoxon can be attributed to both a decrease in peripheral resistance and cardiac output. Decerebration and midcollicular transection were carried out in order to elucidate the site and mechanism of action. The depressor effect of paraoxon seems to be mediated by a central mechanism of action located within the lower brain stem. It is concluded that stimulation of muscarinic receptors in the pontomedullary region gives rise to the observed changes in haemodynamic parameters. Muscarinic receptors in the hypothalamus seem to be of minor importance for the hypotensive action of paraoxon.

Anesthesia↗
PubMed1981

Muscarinic effects of various isoarecaidine esters in sympathetic ganglia.

1 The pressor effects of various tertiary and quaternary isoarecaidine esters in both pithed and anaesthetized rats are reported. In order to elucidate the mechanism of action, various experiments were carried out with the quaternary isoarecaidine methyl ester (Q-4-Me). 2 Treatment with mecamylamine, dexetimide, reserpine and phentolamine abolished or reduced the pressor response to Q-4-Me, whereas pretreatment with cocaine gave rise to a prolonged pressor effect. Plasma noradrenaline levels were significantly increased after the infusion of Q-4-Me. 3 From the results it can be concluded that the pressor effects brought about by the quaternary compounds can be attributed to stimulation of nicotinic and muscarinic receptors in sympathetic ganglia. The consequences of interaction with muscarinic receptors predominate over the effects due to minimal interference with nicotinic receptors by the drug.

Anesthesia↗
PubMed1981

Central cardiovascular effects of physostigmine in the cat; possible cholinergic aspects of blood pressure regulation.

The cental actions of the lipophilic cholinesterase inhibitor physostigmine were investigated by infusing very low doses (0.8 micrograms up to 18 micrograms per kg) into the left vertebral artery of the anaesthetized cat. A dose as low as 2.7 micrograms per kg reduced blood pressure by about 35%. High doses caused bradycardia. Occlusion of the right vertebral artery shifted the dose-response curve to the left. It seems likely that the hypotension was due to stimulation of muscarinic receptors in the pontomedullary region, since pretreatment with dexetimide administered via the vertebral artery strongly reduced the effect. Mecamylamine and the adrenergic blocking agents metoprolol and piperoxan, infused into the vertebral artery, could not reduce the depressor response and the bradycardic action. Both bilateral cervical vagatomy and peripherally applied N-methylatropine did not change the hypotensive action of physostigmine. This observation points towards a reduction of sympathetic outflow as the possible cause of the depressor effect. Atenolol, given intravenously, diminished the bradycardia to a great extent, whereas N-methylatropine did not significantly alter the negative chronotropic action of physostigmine. These results suggest a dominant role for the sympathetic system in reducing cardiac frequency. After intravenous administration, only doses higher than 28 micrograms per kg evoked hypotension, which could not be blocked by intravenously administered N-methylatropine. However, centrally infused dexetimide considerably antagonized this effect, indicating that the hypotension was brought about by a central action and not evoked peripherally. Application of the drug via the external carotid arteries resulted in hypotension after considerably higher doses than those following administration via the vertebral artery, indicating the pontomedullary region as the main site of action. It is concluded that the present experimental data obtained with physostigmine support the hypothesis that ACh might have a transmitter role in the central haemodynamic control.

Acetylcholine↗
PubMed1981

The influence of physostigmine on sympathetic outflow and haemodynamics by an action upon the pontomedullary region of the cat.

Administration of physostigmine into the left vertebral artery of the anaesthetized cat elicited a simultaneous decrease of various haemodynamic parameters. This action seems to be mediated by the sympathetic nervous system since interruption of spinal sympathetic pathways by means of thoracicolumbalectomy prevented both the depressor effect and the negative chronotropic action of physostigmine. Moreover, the simultaneous decrease in blood pressure and splanchnic nerve activity produced additional evidence in support of the involvement of the sympathetic nervous system with respect to the observed changes in haemodynamics. The influence of midcollicular transection and pithing upon the cardiovascular effects of physostigmine confirms the earlier established central mechanism which is located within the lower brain stem. It is concluded that stimulation of structures within the pontomedullary region gives rise to the observed changes in haemodynamic parameters. The sympathetic part of the autonomic nervous system plays a dominant role in the depressor effect of physostigmine.

Animals↗
PubMed1980

The simultaneous infusion of drugs via the left and right vertebral artery of the cat; a modified animal model for the study of possible central actions of drugs upon the lower brain stem.

The development of a modified animal model for the administration of drugs via the vertebral arteries (v.a) of the cat is the subject of the present study. It has been demonstrated that drugs infused via the left v.a. (the "classical" model) accumulate mainly within the left part of the medulla oblongata and pons. This unilateral, leftsided distribution is different from that after intravenous application, since equal drug concentrations are measured at both sides after peripheral administration. Moreover, the results demonstrate that equihypotensive doses of the depressor agent isoarecaidine propyl ester (IAPE) infused either i.v. or via the left v.a. give rise to much higher drug concentrations in the lower brain stem when the latter route of administration is applied. This discrepancy is attributed to the unsymmetrical distribution pattern within the pontomedullary region when the drug is administered via the left and right v.a. Therefore drugs were simultaneously infused via the left and right v.a. Then the aforementioned discrepancy is not observed. Moreover, drug concentrations in the left and right sides are of the same order of magnitude and correspond with those obtained after the equihypotensive dose given i.v. Bilateral infusion of clonidine, arecoline and IAPE into the v.a. results in a significant increase in potency when compared with the administration via the left v.a. Conclusively, the modified vertebral artery model can be considered to be a more appropriate method to test possible central actions of drugs upon the pontomedullary region. The presented administration technique imitates the i.v. route with respect to drug concentrations in this brain region and the corresponding pharmacological effects. However, the dose to be administered is only a fraction of i.v. dose.

Animals↗
PubMed1979

The effects of desmethylimipramine on the pharmacological actions of alpha methyldopa in man.

The effect of pretreatment with the tricyclic antidepressant desmethylimipramine (DMI) 75 mg daily for 3 days on the action of oral methyldopa 750 mg was investigated in a double blind crossover design in volunteers. DMI pretreatment caused a small but not significant increase in supine systolic and diastolic blood pressure and heart rate. However, the effects of methyldopa on lying and standing blood pressure and heart rate were not markedly altered by pretreatment. In particular, the fall in standing blood pressure after methyldopa was present with and without DMI and the sedative action of methyldopa was similar. DMI alone reduced saliva production. No evidence was found that tricyclic antidepressant drugs significantly modify the hypotensive effect of methyldopa in man.

Adult↗
PubMed1979

Comparison between the pressor response and the rise in plasma catecholamines induced by acutely elevated intracranial pressure.

The influence of an abrupt elevation of intracranial pressure (ICP) on arterial blood pressure and on plasma catecholamines was studied and compared both in anaesthetized rats and cats. In rats, the elevation of ICP to 160 mm Hg caused an immediate rise in mean arterial blood pressure (MAP) and heart rate. Plasma noradrenaline and adrenaline also increased, though much slower than the circulatory changes. The duration of the pressor response was reduced after either reserpinization or adrenalectomy and virtually abolished after a combination of both pretreatments. The rise in plasma noradrenaline and adrenaline was virtually abolished in rats pretreated with reserpine or subjected to bilateral adrenalectomy. Acute elevation of ICP up to 160 mm Hg also caused pressor and chronotropic responses in cats, which were reduced by preceding reserpinization and adrenalectomy and abolished by a combination of both pretreatments. The rise in plasma noradrenaline was similar to that in rats, also with respect to its development, which proved to be much slower than that of the circulatory changes. The rise in plasma adrenaline was much less pronounced in cats. Pretreatment with reserpine or adrenalectomy virtually abolished the ICP-induced rise in plasma noradrenaline. Reserpine pretreatment had relatively little influence on the rise in plasma adrenaline but bilateral adrenalectomy virtually abolished it. In venous blood directly obtained from the adrenal gland the rise in plasma noradrenaline ICP elevation caused a rapid increase in plasma catecholamines, which could be reduced by pretreatment with reserpine. Our experiments confirm the hypothesis that the elevation of ICP causes an increase in sympathetic tone. The determination of plasma catecholamines, however, is not an adequate method to study rapidly occurring changes in sympathetic tone.

Adrenal Glands↗
PubMed1978

The central action of various arecaidine esters (arecoline derivatives) on blood pressure and heart rate in the cat. Comparison with the peripheral effects.

The central action of various arecaidine esters (arecoline derivatives) on the cardiovascular system has been studied. Central injection of these cholinergic drugs into the vertebral artery of the cat gives rise to a hypotensive effect, whereas heart rate is not affected. It is concluded that the blood pressure lowering effect is brought about by stimulating central muscarinic receptors. Moreover, the experimental results indicate that the central muscarinic receptors behave in the same way towards their agonists as do the peripheral muscarinic receptors.

Animals↗
PubMed1978

The central actions of nicotine on blood pressure and heart rate after administration via the left vertebral artery of anaesthetized cats. Distribution of nicotine into the brain after central application.

After injection into the vertebral artery of anaesthetized cats, low does of nicotine (10(-9)--10(-8) mol = 0.5--5 micrograms . kg-1) induce potent cardiovascular effects. The hypotensive action is always accompanied by a severe bradycardia. Dose-response curves for these pharmacological actions have been established. It is concluced that nicotinic receptors in the medulla oblongata and pons are involved. Administration of 10(-8) mol = 5 micrograms (radioactive) nicotine/kg into the left vertebral artery gives rise to a specific distribution pattern. Nicotine mainly accumulates into the ponto-medullary area, whereas higher brain regions (hypothalamus) contain only insignificant amounts. The experimental results suggest that the nicotine-like effect of endogenous acetylcholine might play an important physiological part in the central regulation of blood pressure and cardiac frequency.

Animals↗
PubMed1976

Metabolic degradation of propanidid by various tissues. Short communication.

The very short anaesthetic action of 3-methoxy-4-(N,N-diethylcarbamoyl-methoxy)-phenylacetic acid propylester (propanidid, Epantol) is due to its rapid hydrolysis in vivo. In this study, the rates of degradation of this drug under the influence of various isolated tissues have been established. The drug was hydrolysed much more rapidly by liver homogenate than by whole blood or serum. It is concluded that inactivation of propanidid in vivo occurs mainly by the liver, whereas blood esterases play an insignificant part in hydrolyzing the ester. Moreover, it was demonstrated that cardiac tissue is able to hydrolyze the drug as well. It is postulated that the inactivation of propanidid by heart muscle might partly compensate for the severe cardiodepressive action of the anaesthetic agent. A gaschromatographic determination of propanidid has been developed.

Animals↗
PubMed1975

The negative inotropic action of propanidid. influence on calcium movements in atrial tissue.

Propanidid (Epontol), a general anaesthetic agent with a particularly short action in vivo significantly depressed the contraction amplitude of guinea pig isolated atria. A steep concentration-response curve could be established. Contractile force of electrically driven atria (180/min) was reduced by approximately 50% at a propanidid concentration of 3.5 x 10-4 M in the medium. The negative inotropic effect developed rapidly (less than 10 min). At concentrations of 4.5 x 10-4 M and less propanidid hardly reduced the frequency of spontaneously beating atria. The uptake of extracellular 45 Ca by spontaneously beating atria occurred significantly more slowly in presence of propanidid (4.5 x 10-4 M ), whereas the exchangeable calcium fraction remained unchanged. Accordingly, propanidid reduced the rate of exchange of calcium so that less ionized calcium was available for excitation-contraction coupling. Propanidid (4.5 x 10-4 M) accelerated the uptake of 45Ca by isolated plasma membranes, obtained from guinea pig ventricular muscle. Moreover, the binding capacity for calcium by isolated membranes was increased in presence of propanidid. These observations imply that less ionized calcium is available for activation of the contractile system. It is concluded that the negative inotropic action of propanidid is probably due to the drug's influence on membrane function, thus bringing about an important change in cellular calcium metabolism.

Animals↗
PubMed1975

On the mechanism of the negative inotropic action of halothane and propanidide.

1) Halothane and propanidide reduce the contractile force of guinea pig isolated atria in a concentration-dependent manner. The approximate concentrations required to bring about a half-maximal pharmacological effect are within the same order of magnitude as the concentrations found in whole blood during general anesthesia of guinea pigs. 2) It seems most likely that the initial effect of halothane or propanidide occurs at the cell membrane. 3) Halothane and propanidide accelerate and enhance the uptake of calcium ions by the cell membrane, so that less ionized calcium will be available for excitation contraction coupling. This phenomenon readily explains the negative inotropic action of both drugs and confirms the presumption that the cell membrane is the initial site of pharmacological attack.

Animals↗
PubMed1975

Influence of halothane on calcium movements in isolated heart muscle and in isolated plasma membranes.

The influence of halothane on cellular calcium movements was studied in guinea-pig isolated atria and in isolated plasma membrane from guinea-pig myocardial muscle. In spontaneously beating atria halothane (1.6 X 10(-4) M) significantly reduced the rate of 45Ca-accumulation, but the total tissue calcium content and the exchangeable fractions remained unchanged. In isolated plasma membranes the rate of 45Ca- uptake was increased by halothane. Moreover, the binding capacity for calcium was increased as well upon exposure to halothane in concentrations that are sufficiently elevated to depress cardiac contractile force. This finding is interpreted in the sense of a reduced amount of ionized calcium that can be made available for excitation-contraction coupling, owing to the halothane- induced acceleration of calcium binding by plasma membranes. Kinetic experiments in isolated atria had already suggested that halothane probably acts at the level of the outward cell membrane. The changes in membraneous calcium migration may be causally related to the cardiodepressive influence of the anaesthetic agent.

Animals↗