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G Paulet

Publications and source records attributed to G Paulet.

At least 19 recordsLinked to original sources

A proposed mechanism for cardiac sensitisation: electrophysiological study of effects of difluorodichloromethane and adrenaline on different types of cardiac preparations isolated from sheep hearts.

Difluorodichloromethane (FC12) inhaled at high concentrations sensitises, as do numerous other volatile organic compounds, mammalian heart to adrenaline induced arrhythmias. In this study three types of cardiac tissue (spontaneously beating sinusal and Purkinje preparations and stimulated Purkinje fibres) were isolated from sheep hearts and perfused for electrophysiological recording to examine the effect of FC 12. Preparations were perfused alternately with a control solution of physiological fluid and a trial solution with dissolved FC 12, the partial pressure of oxygen remaining identical. Sensitisation to adrenaline was studied by injecting adrenaline at a dose causing a notable effect without producing arrhythmias in the control preparations. Examination of transmembrane potential recordings confirmed that FC 12 inhibits sinus node pacemaker stimulation by adrenaline. Conversely, the adrenaline induced acceleration of latent pacemakers in certain types of Purkinje fibres appeared to be potentialised by FC 12. The various types of arrhythmia observed in vitro were explained by the effect of FC 12 on cell membranes, an affect which can oppose or favour that of adrenaline. These phenomena explain the arrhythmias observed in isolated hearts or whole animal preparations and permit a better understanding of the mechanism involved in cardiac sensitisation to adrenaline induced arrhythmia, a mechanism in which variability in time and location is the essential factor in the FC 12 effect.

Action Potentials↗

Fluorocarbons and cardiac arrhythmia: does difluorodichloromethane (FC 12) inhibit cardiac metabolism?

Certain fluorocarbons, such as difluorodichloromethane (FC 12), depress the cardiovascular system by diminution of all the transmembrane ionic conductances in cardiac tissues. Does FC 12 also inhibit active transport and thus enzymatic activity and cellular energy? We measured phosphocreatine (PC), adenosine triphosphate (ATP) and cyclic adenosine monophosphate (AMPc) in rat hearts. Rats were randomly divided into 4 groups; 2 control groups: one breathing a mixture of oxygen (21%) and nitrogen (79%) (group C) and the other breathing the same mixture but simultaneously perfused with 1 microgram/kg/min. epinephrine (groupe E-C); 2 trial groups T and E-T where nitrogen was replaced by FC 12. The maximal FC 12 concentration of 720 micrograms/ml in arterial blood produced no significant difference in the concentrations of these three metabolites compared with controls.

Animals↗

Mechanism of liposoluble drugs and general anaesthetic's membrane action: action of difluorodichloromethane (FC 12) on different types of cardiac fibres isolated from sheep hearts.

The effect of difluorodichloromethane (FC 12), a chemically stable aerosol propellant which has long been considered innocuous, on several types of cardiac fibres isolated from sheep hearts after preparation in a nutritive solution was studied. Modifications in resistance and transmembrane potentials suggested a mechanism of FC 12 action. Physical constraint on membrane structures produced by high FC 12 concentrations from simple dissolution in the internal lipid layer explain modifications in cardiac membrane properties. Variable effects of FC 12 with localisation and time on automatism, excitability, and conduction in various types of cardiac tissue agreed with earlier observations of the depressive and arrhythmia effect of this gas on isolated and in situ hearts.

Action Potentials↗

[Comparative study of four effort tests on nine-year-old children. The value of systolic tension time (author's transl)].

Simple effort tests were carried out on 9-year-old children to measure the systolic tension time (STT) and to judge the accuracy and limitations of such a test by comparing it with other measures more commonly employed in France for the same age group: Pachon-Martinet, Ruffier-Dickson, and maximal oxygen uptake (VO2max), the latter (estimated indirectly) serving as the standard of reference. Subjects stepped onto and off a stool 40 cm high, 24 times per minute; immediately thereafter the heart rate per minute and the arterial systolic pressure (mm Hg) were measured, and the product (the systolic tension time) was obtained. At the age of 9 years, 95% of children have an STT of between 13 000 and 25 000. This test, besides the ease with which it can be performed in daily experimentation, has the advantage of giving results that are at once more precise and more significant than the two standard tests of Pachon-Martinet and Ruffier-Dickson because the quality of the experiment is more satisfactory, because autonomic factors have less impact, and because its discriminative value is higher since only the STT provides a satisfactory correlation with VO2max. The test also fulfills the various requisites of an effort test: it can help to trace a poor cardiovascular response to effort and, because of its selective nature, it can also provide a convenient means of supervision of young athletes. In practice, the test should be complemented by a study of the first 3 min of recovery, as this was the only part of the test showing a difference between boys and girls, whether trained or not.

Child↗

[Effect of difluorodichloromethane (FC 12) on the cardiac cellular electric activity of mammals].

The cardiotoxicity of high concentrations of inhaled difluorodichloromethane (FC 12) has now been acknowledged. In the present study, the effects of FC 12 on the electrical activity of cells in the atrial and ventricular myocardium of anesthetized rats were recorded with "flexibly mounted" intracellular microelectrodes. The major phenomena observed in both types of cells were: a distinct decrease in the diastolic potential, a decrease inthe amplitude of the action potential, modifications in the shape of the action potential. Analysis of the simultaneously obtained electrocardiogram specifies the rhythm abnormalities which consist of an important decrease in the atrio-ventricular conduction and changes in the myocardial excitability. The cardiotoxicity of FC 12 is assumed to affect passive or active transmembrane ionic movements. Possible mechanisms are suggested here.

Animals↗

[Subacute alcoholic intoxication in rats: effect of an intravenous injection of glucagon or adrenaline].

We have studied the hyperglycemic effect of glucagon (20 microgram/kg) and adrenaline (5 microgram/kg/mn/3 mn) on the rat subjected to a subacute alcoholic intoxication (6,4 g/kg by day during 12 days). The hyperglycemic action of the glucagon is increased while that of the adrenaline slightly decreased. So, the alcoholic intoxication allows to dissociate the both mechanisms of the glycogenolytic action of both hormones. Two hypothesis are brought forward in the discussion.

Alcoholism↗

[Role of endogenous adrenaline in cardiac arrhythmia induced by dichlorodifluoromethane (FC 12) in mammals].

During the inhalation of normally oxygenated gas mixtures containing light or middle concentrations of FC 12, the presence of perfused epinephrine is necessary to induce cardiac arrhythmia in rabbits and dogs. The only inhalation of normally oxygenated gas mixtures containing a very high concentration of FC 12 produces in rabbits and dogs an important decrease in arterial pressure, tachycardia, a fall in respiratory amplitude, an acceleration reflex of respiratory frequency and cardiac arrhythmia. The same experiments in baro and chemodenervated animals show that : respiratory depression due to FC 12 still occurs, but not through the arterial chemoreceptors ; tachycardia has a reflex origin : barodenervation reveals the negative chromotropic effect of FC 12 and increases the fall in arterial pressure, mainly due to the negative inotropic effect of FC 12 ; adrenaline is necessary for FC 12-induced arrhythmia : barodenervation suppresses tachycardia due to the release of endogenous epinephrine and abolishes any arrhythmia.

Animals↗

[Development of liver glycogen reserves in rats subjected to chronic alcoholic intoxication].

Literature offers many but very different informations about the effects of alcohol on the hepatic carbohydrates metabolism. Therefore we have tried to observe, in process of time, the evolution of the hepatic glycogen reserves on rats intoxicated by ethanol 40% during variable durations. Stuffing is made by oesophageal way at the rate of 6,4 g/kg/day. During this period of poisoning, we note a significant increasing of the hepatic glycogen reserves.

Alcoholism↗

[Cardiac arrhythmia in the rabbit under the effect of adrenaline and difluorodichloromethane (FC12)].

Inhalation of gas mixtures containing different concentrations of FC12 by anesthetized and normally oxygenated rabbits produces blood levels of FC12 which are stable and proportional to the rate of FC12 in the mixture. From the arterial concentration of 80 microgram/ml FC12 (10 % FC12) mixture) and over, FC12 alone causes effects proportional to doses: arterial pressure decrease with tachycardia; slight morphological alterations of the electrocardiogram at high concentration. Arrhythmia never occurs under the action of FC12 alone even at maximum arterial concentration reached here: 235 microgram/ml (40 % FC12 mixture). Recorded disturbances are always reversible. The intravenous perfusion of epinephrine alone evokes the appearance of premature contractions at only very high doses: 12 microgram/kg/min. The presence of FC12 in blood conjoined with epinephrine induces the inhibition of the hypertensive action of epinephrine at high concentrations and lowers the arrhythmogenic threshold. Both parameters interfere: the arrhythmogenic dose of epinephrine is a function of blood levels of FC12.

Animals↗

[Cardiac arrhythmia in dogs under the action of adrenaline and difluorodichloromethane (FC 12)].

Inhalation of gas mixtures containing different concentrations of FC 12 by anesthetized and normally oxygenated dogs produces blood levels of FC 12 which are stable and proportional to the rate of FC 12 in the mixture. From the arterial concentration of 40 microgram/ml FC 12 (5 % FC 12 mixture) and over, FC 12 alone causes effects proportional to doses: arterial pressure decrease with tachycardia. At high rates of FC 12 tachypnoea and slight morphological alterations of the electrocardiogram can be recorded. Arhythmia never occurs under the action of FC 12 alone even at maximum arterial concentration reached here : 230 microgram/ml (40 % FC 12 mixture). Recorded disturbances are always reversible. The intravenous perfusion of epinephrine alone evokes the appearance of premature contractions at the only dose of 5 microgram/kg/mn. The presence of FC 12 in blood conjoined with epinephrine induces the inhibition of the hypertensive action of epinephrine at high concentration and lowers the arhythmogenic threshold. The dog is clearly more sensitive than the rabbit to the arhythmogenic action of epinephrine and FC 12. The required rates of epinephrine and FC 12 validate the hypothesis of cardiac sensitization by FC 12 to the arhythmogenic action of circulating adrenaline to explain the cases of sudden "sniffing" deaths in man.

Animals↗

[Action of difluorodichloromethane (FC 12) and of adrenaline on the isolated rabbit heart].

Does difluorodichloromethane (FC 12) sensitize the cardiac muscle in vitro to epinephrine-induced arrhythmia ? We have tried to answer this question by comparing : the action of epinephrine alone on the isolated rabbit heart perfused by an ordinary nutritive solution and the action of epinephrine on the heart perfused by a nutritive solution containing various concentrations of FC 12. The results are: 1) the general action of epinephrine (inotropic and chronotropic positive effects, increase of coronary flow) is not significantly modified by the action of FC 12. 2) FC 12 does not sensitize the rabbit heart in vitro to the arrhythmogenic action of epinephrine. The few cases of arrthymia recorded under the action of adrenalin do not necessarily occur in the presence of FC 12, but rather depend on the weakened state of the preparation.

Animals↗

[Fluorocarbons in question].

In this study, two fluorocarbons (FC): difluorodichloromethane (FC 12) and monofluorodichlormethane (FC 11) are mainly concerned. These products are extensively used and we attempt to demonstrate their absence of acute, subacute and chronic toxicity as well as teratogenic action. After inhalation, the FC rapidly diffuse into the blood, cerebrospinal fluid and all the "milieu interieur" where a balanced condition is quickly established. Only a few reactions, all reversible, concerning respiration circulation, nervous system and metabolisms are observed when the concentrations in the air is greater than 20% for FC 12 and greater 5% for FC 11. The eliminations of these gase from the body is completed 20-50 mn after fresh air is reinhaled. The problem of the "sudden sniffing Death" is finally taken into consideration. They probably are due to the stopping of the heart by ventricular fibrillation, a consequence of a direct and proper action of the FC on the heart or a sensibilisation of the heart to adrenaline. However this sensibilisation necessitates the presence of more than 40 microgram of FC per ml of blood, concentration never obtained in the most intensive use of aerosols.

Animals↗

[Action of the fluorocarbons, 12 (difluorodichloromethane) and 11 (monofluorotrichloromethane), on smooth muscle].

We have studied the action of difluorodichloromethane (F12) and monofluorotrichloromethane (F11) on the rat isolated uterine muscle and the rabbit isolated duodenum. Both gases in the nutritive solution after the functioning of these organs in a way which is, moreover, non identical. On the uterus both gases show an inhibitory effect against the spontaneous contractions. On the duodenum, both gases inhibit the phasic contractions but the basal tonus is strongly increased by F12, and on the contrary reduced by F11. The action is a musculotrop one and quite reversible in every case. Both gases do not modify the action of acetylcholin, epinephrin and histamin.

Acetylcholine↗

[The effect of difluorodichloromethane (FC 12) on isolated rat and rabbit heart].

We have tried to determine if dichlorodifluoromethane (F.C. 12) might have an effect in vitro on the isolated rat and rabbit hearts. The direct action of F.C. 12 on the heart in vitro is similar in both rats and rabbits. It occurs at doses such as 20 +/- 10 mug/ml (rat) and 35 +/- 5 mug/ml (rabbit). F.C. 12 depresses the strength of the myocardial contractions; the effect is reversible at low concentration (less than 60 mug/ml) but irreversible at high concentration (greater than or equal to 120 mug/ml). It also causes a slight bradycardia, but no significant effect on the basal tonus. At high concentration, F.C. 12 may produce arrhythmia : this action occurs more readily in the rat heart than in the rabbit heart.

Animals↗