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Biomedical subjects

L Wouters

Publications and source records attributed to L Wouters.

At least 73 records · Page 4Linked to original sources
PubMed1984

Cardioprotective effects of mioflazine during 1 h normothermic global ischaemia in the canine heart.

The cardioprotective effects of mioflazine, a recently developed cardiovascular drug, were investigated in 41 anaesthetised open chest Beagle dogs subjected to 1 h normothermic global myocardial ischaemia. The severity of the model is evidenced by the finding that only one out of 20 control dogs could be weaned from extracorporeal bypass. Oral pretreatment with mioflazine (2.5 mg X kg-1) resulted in complete functional recovery in 17 out of 20 animals. Biochemical analysis of left ventricular biopsies taken before, during and after aortic cross clamping showed a preservation of purines and a better recovery of ATP, ATP/ADP X Pi ratio and energy charge (p less than 0.05) in the pretreated animals. Morphological and cytochemical assessment of the myocardium demonstrated that the ultrastructure of the sarcolemma and its calcium binding capacity is remarkably well preserved in the drug treated animals. These results indicate a strong cardioprotective effect of mioflazine. The biochemical, cytochemical and ultrastructural findings suggest an interaction of the drug with the sarcolemma.

Animals↗
PubMed1984

Multivariate analysis of angiographic, histologic, and electrocardiographic data in patients with coronary heart disease.

In 61 consecutive patients undergoing aortocoronary bypass grafting, angiographic and electrocardiographic (ECG) changes were studied. Histologic delineation of myocardium was obtained by analysis of transmural biopsy specimens acquired at the time of surgery. The use of principal-component analysis revealed three definite groups of patients. Group I comprised patients with histologic findings associated with severe left anterior descending coronary artery (LAD) stenosis, without abnormal wall motion or ejection fraction. ECG abnormalities were limited to ST changes. Group II comprised patients with severe myocardial cell degeneration with only modest fibrosis associated with severe LAD stenosis and severely impaired wall motion. The incidence of infarction on the ECG was low. Group III patients had important myocardial cell degeneration with severe fibrosis associated with severe LAD stenosis, severely depressed wall motion, and significantly impaired ejection fraction. In this group there was a high incidence of infarction apparent on the ECG. Postoperative follow-up (24 months) showed a total survival of 94.4% in group I, 92.8% in group II, and only 72.7% in group III. This identification of subtypes of coronary artery disease seems to be helpful in estimating patient prognosis after coronary surgery.

Adult↗
PubMed1984

Cardiac and haemodynamic effects of intravenous administrations of flunarizine in closed-chest anaesthetized mongrel dogs.

This study was performed to evaluate the cardiac and haemodynamic effects of 1-cinnamyl-4-[bis(p-fluorophenyl)methyl]piperazine dihydrochloride (flunarizine, Sibelium ). The compound was dissolved in distilled water acidified with tartaric acid in a concentration of 2 mg/ml (pH 1.8) and administered intravenously in cumulative doses of 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Flunarizine induced systemic vasodilatation dose- relatedly starting with a dose of 0.1 mg/kg i.v. as indicated by the decrease in systemic vascular resistance, while this compound had no vasodilating properties in the pulmonary circulation. Flunarizine caused an increase in heart rate following the administration of the higher doses. This effect is probably reflexogenic in nature and secondary to the decrease in aortic blood pressure. As a consequence the oxygen demand of the myocardium enhanced after these high doses of flunarizine as indicated by the increase in pressure-rate product. Flunarizine did not affect the contractility and the conduction of the heart in the doses of 0.03 up to and including 1.0 mg/kg i.v., but could have some negative inotropic properties at the highest dose used. The end-tidal CO2 concentration in the expired air increased after the administration of 0.3 up to and including 3.0 mg/kg i.v. From these results, it is concluded that flunarizine has systemic vasodilating properties without any cardiac effects at doses from 0.03 up to and including 1.0 mg/kg i.v.

Animals↗
PubMed1984

Serotonin-induced blood flow changes in the rat hindlegs after unilateral ligation of the femoral artery. Inhibition by the S2 receptor antagonist ketanserin.

Collateral arteries can clearly be visualized in corrosion cast material after ligation of the femoral artery in rats. To characterize the influence of serotonin on the blood circulation under the experimental condition of unilateral ligation, we performed intermuscular thermoflow measurements. The data showed that intraperitoneal serotonin (8.7 and 20 mg.kg-1) injection markedly reduced the muscle temperature in both hindlegs. However, the effect was significantly more pronounced on the ligated side, where the blood was supplied through a collateral circulation, than on the non-ligated side with its normal arterial vasculature. Almost identical changes were obtained in rats with an early as well as in animals with a more advanced stage of collateral development (challenge with 8.7 mg.kg-1 serotonin). Evans blue dye experiments and angiographic data further revealed that, after challenge with 20 mg.kg-1 serotonin, the severe temperature decrease at the ligated side probably reflected a nearly complete blockage of blood supply. Pretreatment with the S2 receptor antagonist ketanserin (2.5 mg.kg-1) resulted in a significant reduction in the extent and duration of the serotonin-induced temperature decrease as revealed by the temperature measurements; such a treatment inhibited also the blockage in blood flow as seen with the other techniques. This study shows that serotonin, through its vasoconstrictive properties, can restrict the blood flow to the lower extremities of the rat, particularly when the blood is supplied through collateral circulation. This probably results in moderate to severe skeletal muscle ischaemia. It also suggests that the vasoconstriction is not only important in the inhibition of collateral blood flow in recently established collaterals but also in collateral vessels in a more advanced stage of development. The in vivo vasoconstriction and subsequent reduction of the blood supply caused by serotonin can be effectively counteracted by pretreatment with ketanserin.

Angiography↗
PubMed1983

Flunarizine in the treatment of vertigo.

Experience with flunarizine, a selective calcium-entry blocker, in the treatment of dizziness is reviewed. Clinical efficacy was predicted in pharmacological studies both in rabbits and humans: torsion swing or caloric induced nystagmus were significantly suppressed by flunarizine. Open therapeutic findings, using clinical and electronystagmographic or audiographic assessments as well, showed that flunarizine is of benefit to patients with vertigo of labyrinthine as well as of cerebrovascular origin. These results were confirmed in double-blind controlled trials. Flunarizine, either started with a loading dose gradually decreased thereafter, or given at a fixed 10 mg. dose schedule was proven to produce rapid improvement of dizziness and unsteadiness and to be tolerated very well.

Animals↗
PubMed1982

Enhanced platelet turnover and prostaglandin production in spontaneously hypertensive rats.

The anti-hypertensive effect of ketanserin, a selective 5-HT2 antagonist, both in experimental and human pathology (1,2) could implicate the blood platelets as a source for peripherally available 5-hydroxytryptamine (5-HT), acting to increase peripheral vascular resistance (3). Therefore we examined various blood platelet parameters in spontaneously hypertensive rats in comparison with normotensive Wistar rats.

Animals↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.

Acidosis↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the epileptoid activity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.

Acidosis↗
PubMed1975

Unusual mechanism of hypotensive activity exerted by erytrho-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-ET-a1-4-piperidyl)-2-benzimidazolinone (R 28935).

In the dog, erythro-1-[2-(1,4benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935) lowers the blood pressure for several hours at dosages of 80 mug/kg when injected intravenously, of 10 mug/kg when injected into the vertebral artery and of 1.25 mug/kg when injected suboccipitally. No alpha- or beta-receptor blocking activity can be elicited at these doses. The carotid occlusion reflex is markedly reduced by low doses of R 28935 (40 to 80 mug/kg i.v.), whereas the pressor response elicited by electrical stimulation of the hypothalamus remains unimpaired. The hypotensive effect of R 28935 is not antagonized by piperoxan, desmethylimipramine or nalorphine. This lowering of the blood pressure is associated with a decrease of the peripheral vascular resistance and with a slight tendency towards bradycardia. It is concluded that R 28935 is a potent blood pressure lowering drug, acting on the brain stem, presumably in the pontomedullary region--although the drug has no alpha-sympathomimetic activity.

Animals↗
PubMed1975

Proceedings: The effects of hypothalamic and reflexogenic hypertension on renal and femoral circulation.

In anaesthetized dogs, electrical stimulation of the median posterior hypothalamus provoked hypertension accompanied by a decrease of renal blood flow and an increase of femoral blood flow. Similar hypothalamic reactions occurred after bilateral cervical vagotomy or after atropine, 2 mg/kg i.v. During reflexogenic hypertension induced by bilateral carotid occlusion in bivagotomized dogs, the renal and femoral blood flows were not significantly modified. The decrease of the renal blood flow and the increase of the femoral blood flow, during hypothalamic stimulation were greatly reduced or reversed after R 28935 equals erythro-1-(1--e12-(1,4-benzodioxan-2-yl)-2-OH-Et]-4-piperidyl)-2-benzimidaxolinone, 80 mug/kg i.v., but not after clonidine, 5 mug/kg i.v.

Animals↗