Cardiac depressant effects of some recent aminoglycoside antibiotics.
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Biomedical subjects
Publications and source records attributed to J Descotes.
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The myocardial depressant action of aminoglycosides has been known for a number of years but there was no available data on newer derivatives. We have thus studied the contractile responses of isolated guinea pig left atria to increasing concentrations of gentamicin, tobramycin, lividomycin and amikacin (0.02, 0.04, 0.08, 0.13, 0.17 and 0.22 mM). Our results are consistent with those of previous workers and show that newer aminoglycosides do exert a similar depressant action. As gentamicin and tobramycin are more depressant than lividomycin, then amikacin at similar concentrations, no clear-cut difference was obtained when respecting a relative range of concentrations mimicking that of clinical situations. However, these depressant effects were attained using concentrations far exceeding those reached in man.
In search for an effective treatment of human poisonings with ajmaline, a potent antiarrhythmic drug, the use of specific antibodies as neutralizing agents was explored in a preliminary animal model. For this purpose, New Zealand white rabbits were immunized with the antigen obtained after coupling the 17-hemisuccinate ester of ajmaline-21-acetate to bovine serum albumin, whereas other rabbits were immunized with the protein carrier only. While seven control rabbits receiving 0.625 mg/kg/min. ajmaline intravenously until death, died within 54.8 +/- 5.2 min. death was delayed until 137.7 +/- 15.5 min in seven ajmaline bovine serum albumin-immunized rabbits (p less than 0.001). Three bovine serum albumin-immunized rabbits behaved as controls. These results provide evidence that an immunological protection against ajmaline toxicity can be obtained in laboratory animals.
The effects of intravenously infused succinylcholine (SCh): 1 mg/kg/minute during 30 minutes were assessed in anesthetized dogs on spontaneous heart rate, conduction within the atrio-ventricular node and the His-Purkinje system and on atrial (AERP) and atrio-ventricular (AVERP) effective refractory periods with varying levels of vagal tone and under mild hyperkalemia. 1) The heart rate which was not affected by SCh in the absence of vagal tone was by contrast increased by 50 p. cent when vagal tone was maintained. Under hyperkalemia, the vagolysis-mediated tachycardia did not prove more marked. 2) The conduction velocity, which was never modified by SCh in either the atria or the His-Purkinje system, was always accelerated with vagal tone. This acceleration is directly related to the vagolytic properties of SCh, but also partly to a mild hyperkalemia. The changes of potassium blood levels tend to reverse the potassium outflow due to the parasympathetic neuromediator. 3) The AERP was was lengthened by SCh and hyperkalemia; the latter impaired the outflow of potassium ions responsible for repolarization. The AVERP was always shortened when the vagal tone is maintained, however less largely under mild hyperkalemia which limits SCh anticholinergic effect owing to its own anticholinergic action.
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The effects of diltiazem, a new slow channel inhibitor, on the cardiac conduction and refractoriness have been studied using His bundle recordings and the extrastimulus method. In order to determine the role played by possible changes in vagal tone, diltiazem (0.15 mg.kg-1, followed immediately by a 30 min infusion of 0.01 mg.kg-1.min-1) has been administered intravenously to six atropinized dogs, anesthetized with chloralose (100 mg.kg-1) ("atropine group") and to six others which were given chloralose (80 mg.kg-1) and dextromoramide (0.1 mg.kg-1) to ensure the persistence of vagal tone ("vagal tone group"). In the "atropine group", atrioventricular (AV) nodal conduction time increased by 137% and AV node effective refractory period by 55%. Heart rate was slowed down by 15% and arterial pressure fell slightly. In the "vagal tone group", the only significant changes were a 26% increase in AV nodal conduction time and a slight fall in arterial pressure. Inhibition of the slow channel accounts for the effects of diltiazem within the "atropine group". A reflex decrease in vagal tone is probably responsible for the somewhat different results observed in the "vagal tone group". Diltiazem resembles verapamil and should share its antiarrhythmic properties.
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Effects of mild hyperkalemia on conduction velocity, effective refractory periods (ERPs) and sinus rate were studied on 16 anesthetized dogs, using endocavitary His bundle recordings, the extrastimulus method and standard electrocardiogram. Six dogs were placed under acetylcholine infusion (300 micrograms/kg/min) (ACh group), 10 received atropine sulfate 0.2 mg/kg intravenously (atropine group). Intraventricular conduction time, ventricular ERP and QRS duration of the EKG were studied on 7 other open-chested dogs (ventricular group). During a 60 min potassium chloride infusion (0.025 mmol/kg/min, 30 min, then 0.05 mmol/kg/min, 30 min), following observations were made: - In the ACh group, AV node conduction time (A-H interval) decreased by 20% and AV node ERP by 17%, whereas, in the atropine group, the former parameter was not affected and atrial ERP increased by 29%. - At the same time, sinus rate increased in the ACh group and was unaffected in the atropine group. - Conduction times in atrial contractile tissue (S-A interval), His-Purkinje system (H-V interval) and ventricular contractile tissue, like ventricular ERP, exhibited no variation or very slight, occasionally biphasic variations under both conditions. These results can be accounted for by an "anticholinergic" effect of mild hyperkalemia which is discussed.
The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
The nature and characteristics of the tissue which develops on the inner surfaces of vascular arterial prostheses have been investigated by means of histological and biochemical criteria. Velour prosthetic tubes were implanted as aortic segmental replacements in the dog. On the 60th postoperative day, a neointimal layer of collagen covered with flattened endothelial-like cells was noted. However, despite this morphological evidence the microsomic and cytosolic enzymes implicated in the biosynthesis of glycosamino-glycuronoglycans were significantly modified in comparison with the normal aortic wall. The marked decrease in enzymes corresponding to the initiation of the glucidic linkages suggests that the biosynthesis of the macromolecular components responsible for the normal blood vaessel interfact was impaired in these newly developed tissues. Therefore, it is suggested that this newly developed tissue cannot be considered as a true vascular endothelium.
The Sparks-Mandril blood vessel precursor system, an autogenous tissue growth-promoting device, in spite of its ingenuity and its surgical elegance, has received only limited usage. At technique for peripheral blood vessels by several authors. In the latter period, this laboratory also undertook similar work. The results of seven implantations in dogs and two in patients are reported here in the context of a program on the evaluation of blood vessel substitutes, their mode of operation and their long term performance. The clinical status and the pathology of the grafts at time of failure were investigated using techniques of scanning electron microscopy. This work confirms the findings of other centres regarding the generally unsatisfactory performance of the Sparks-Mandril system. Possible causes for failure in mandril-formed blood vessels are discussed.
Controversy persists between partisans of medical treatment and partisans of wide surgical indications. In iliocaval phlebitis, the authors defend surgery insofar as the operation is restorative, whilst remaining "reasoned" in terms of the lesions and the numerous factors involved. Experience of 90 cases of phlebitis treated over the past two years has shown that restoration may be obtained and maintained in more than half the number of cases and that prophylactic partial venous occlusion proved necessary in only 30% of cases. Absence of any deaths confirmed the value of this approach.
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The effect of thioridazine on sinusal automaticity, myocardial excitability and auriculoventricular conduction have been studied in dogs by measuring the spontaneous heart rate, the effective refractory period of the atrial contractile tissue, the time of auriculonodal and infrahisian conduction. Chloralose anaesthetized dogs were administered 10 mg/kg thioridazine hydrochloride via intravenous route. While sinusal automaticity was not altered, conduction times were prolonged in the suprahisian and mainly the infrahisian part and the atrial refractory period increased. These effects are related to quinidine-like properties and consistent with cardiotoxic effects previously reported in clinical practice.
The effect of levomepromazine on sinusal automaticity, myocardial excitability and auriculoventricular conduction have been studied in dogs by measuring the spontaneous heart rate, the effective refractory period of the conduction system, the time of auriculonodal and infrahisian conduction. Chloralose-anaesthetized dogs were administered 5 mg/kg levomepromazine via IV route and 10 mg/kg one hour later. While sinusal automaticity is never altered, the other parameters studied were modified only when high doses were used. Therefore these quinidine-like effects are very unlikely to come up even following suicidal massive ingestion of levomepromazine.
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The severity of ischemic lesions in the spinal cord justifies attempts at its surgical revascularization. The experiments consisted of: (1) creating devascularization of the conus medullaris by ligation of all the lumbo-sacral collaterals of the aorta, and (2) revascularizing the lumbo-sacral rachidian circulation by performing an end-to-side anastomosis between the caudal mesenteric artery and the 5th left lumbar artery (from which in the dog the Adamkiewicz artery generally arises). After two-months, the patency rate of the 20 cases was 85%. Such a procedure of revascularization could be useful in man in cases of interruption of the arterial supply of the spinal cord.
The authors detail their concepts of the physiopathology, the diagnostic methods and the treatments of grave puerperal phlebitis, having seen six cases in their two departments recently. They consist of 5 cases of iliofemoral thrombosis, 2 of whom were diagnosed during their pregnancies and 3 others whom were diagnosed after delivery. One of these died of pulmonary embolus: and there was one case of thrombosis of the right ovarian vein during post-partum. Over and above the classical factors that predispose to this condition in pregnancy, the authors draw attention to the anatomical constitutional factors that have been observed by Cockett in the physiopathology of these cases. The diagnosis is made using non-invasive methods: Doppler, plethysmography, labelled fibrinogen and isotope phlebography after delivery, supplemented when the results are positive by radiography of the iliac and vena caval systems which alone gives a precise diagnosis of the site. Therapeutic possibilities change according to the time that the condition is perceived, according to the topography of the lesions, and according to the existence or non-existence of moving thrombi. The treatment is directed to avoiding the complications of emboli and to preventing secondary functional sequellae. Finally the gynaecological problems of contraception and of further pregnancies are considered.