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Biomedical subjects

M C Auclair

Publications and source records attributed to M C Auclair.

12 recordsLinked to original sources

Chronotropic effect of histamine on cultured neonatal rat heart cells.

The positive chronotropic effect (PCE) of histamine in cultured neonatal rat heart cells was monitored using a microscopic method as well as an electro-optically recording device. The action potential frequency was also measured (by means of microelectrodes). An increase in PCE was noted when histamine (from 1 X 10(-6) M to 1 X 10(-5) M) was added to the cells. However, higher concentrations (from 1 X 10(-5) M to 1 X 10(-4) M) were less effective. The PCE of histamine was reduced by pretreating the cells with antihistaminic drugs. H1-blocking agents (promethazine and mepyramine) were more potent than H2-blocking drugs (metiamide and cimetidine). In addition, the PCE of histamine was abolished when the cells were in presence of high K+ medium (26 mEq) but contraction and action potential amplitudes were increased. Our results demonstrate that these cultures respond to histamine and that this response is abolished by antihistaminic drugs thus suggesting the H1 and/or H2 receptors may be present in the neonatal rat heart cell cultures.

Animals

[Reduction of isoprenaline induced tachycardia in pregnant rats. Role of a serum factor].

The in vivo isoprenaline (50 microgram/kg) induced tachycardia (beta 1 adrenergic stimulant effect) was decreased in pregnant (20th day) Rats compared to non pregnant Rats. The in vitro positive chronotropic effect of isoprenaline (10 ng/ml) on cultured Rat heart cells was abolished by pregnant Rat serum whereas progesterone (0.10 to 5 microgram/ml) or oestradiol (0.1 to 25 microgram/ml) were ineffective. The decreased beta 1 adrenergic responsiveness in pregnant Rats could be related to a seric factor, different from these two hormones.

Animals

[Biological determination of the beta blocking activity of human serum].

A method of biological assessment of the Beta blocking activity of human serum is reported. It is based on the catecholamine response of rat myocardial cells in culture, incubated in the serum to be tested. Its advantage is that it takes into account all block-blocking substances present in the serum, not only the drug itself but also its possible active metabolites. The results obtained by this method in 10 healthy subjects after 60 mg penbutolol were compared with those given by chemical dosage and ergometry. The ergometric and biological changes were parallel from the 2nd and the 8th hour while the serum levels of the drug rapidly. This discordance could be due to the presence of an active metabolite, 4-hydroxy-penbutolol.

Adrenergic beta-Antagonists

Reversal by calcium of rat heart cell dysfunction induced by human sera in septic shock.

Twenty human sera obtained during the first 24 hours following clinical onset of different septic shocks were evaluated for their effects on electric an mechanical activities of rat heart cell cultures. Possible antagonistic action of calcium was tested on these effects. The results showed that septic shock sera, when compared to normal sera, increased action potential duration and depressed contractility of beating cardiac cells. Addition of calcium reversed these two actions, though markedly higher concentration was needed for depressed contractility. The in vitro deleterious effects of septic shock sera on cell cultures were related neither to decrease in extracellular calcium, since total calcium level was moderately below normal values, nor to inhibition of low calcium channel, since the action potential was not suppressed in presence of K+ excess. This study suggests the involvement of humoral factors mimicking the cardiac effects of low calcium concentration. If calcium is involved in in vitro cardiac dysfunction, it could result only from a decrease of available calcium in cytosol.

Action Potentials

Inhibited response to isoproterenol and altered action potential of beating rat heart cells by human serum in septic shock.

Human serum, obtained within 24 hours after the onset of septic shock, was evaluated for its effects on the chronotropic response of cultured rat myocardial cells to isoproterenol. Transmembrane action potential (AP) was measured in some experiments. Sera obtained after the first four to five hours, when central venous pressure (CVP) was normal or high, inhibited increased cell beats, while this property was not evidenced for samples taken soon after septic shock when CVP was low. Sera were also found to alter AP in much the same way as Sotalol, an adrenergic beta-blocking drug. These two effects were never observed with control sera obtained from healthy male adults at rest. These findings demonstrate that sera from patients in septic shock depress the beta-adrenergic response of rat myocardial cells, after the early phase of septic shock characterized by sympathoadrenergic activity. They strongly suggest the mediation of unidentified humoral factors, which might interfere in the pathogenesis of myocardial dysfunction during the intermediate phase of septic shock.

Action Potentials

[Increase in spontaneous beating frequency in rat heart cells cultured in homologous serum].

Rat serum at different concentrations added to cultured Rat heart cells medium increased spontaneous beating frequency of myoblasts. This increase occurred instantaneously and lasted more than 24 hrs. It was related to the serum concentration used. Electrophysiological recording showed a decrease in the iso-electric phase duration of membrane potential, with no change in action potential. In spite of the beating frequency increase, cells remained sensitive to the chronotrope positive action induced by Isoprenaline. There was no difference between male and female sera. The global results could partly be explained by the action of Ca++ in Rat serum.

Action Potentials

Inhibitory action of human serum on the isoprenaline-induced chronotropic effect in cultured rat heart cells. Influence of sex and pregnancy.

Cultures of beating rat myocardial cells brought into contact with various human sera during 24 hours were infused with isoprenaline. The isoprenaline-induced positive chronotropic effect (IIPCE) was not found with all sera. IIPCE was present in all the male sera, but was absent in the cases of clinically beta-blocked pindolol treated men. IIPCE was present only in about 50% of the female sera, menopaused or not. IIPCE was absent in 95% of the sera of pregnant women in the late phase of pregnancy. This suggests the presence in female sera, especially during pregnancy, of a circulating factor capable of "in vitro" inhibition of isoprenaline-induced positive chronotropic effect.

Adult

[Action potential changes induced by a polyflavane on normal or hypoxic guinea pig myocardial strips].

On normal isolated or stimulated Guinea-Pig myocardial strips, a polyflavane extracted from Poterium spinosum (Rosaceae) increased the duration of the action potential plateau phase. Such a modification was also elicited on hypoxic strips; in this case it did not depend on the glucose concentration in the medium; it could be related to an effect on the slow calcium-sodium channel.

Action Potentials

[Characteristics of transmembrane potential of newborn rat cardiomyoblasts which have been cultivated for one week].

The effect of different media on transmembrane potentials and dV/dt of 7-day cultured rat heart cells was studied by means of microelectrodes. The cells appeared sensitive to K& variations, very sensitive to MnC12 and decreased Ca2&, sensitive to lack of serum and oxygen but quite insensitive to lack of glucose and relatively insensitive to tetrodotoxin. These observations suggest that action potentials are principally due to slow inward current. The cells never responded to decreased Na& by decreasing dV/dt but by depolarizing the membrane. It seems therefore that Ca2 ion plays the most essential role in the genesis of action potential and that the rapid sodium channel is relatively unimportant in case of cardiomyoblasts.

Calcium

[Effect of phascoline and phascolosomine, new natural guanide derivatives, on cultured rat cardiac cells].

Two new biological guanido compounds from sipunculid worms, phascocoline [N-(3-guanidinopropionyl)-2-hydroxy-n-heptylamine] and phascolosomine [N-(3-guanidinoisobutyryl)-2-methoxy-n-heptylamine], have been tested for their effect on cultured rat heart cells. Both compounds were found to stop the beating of the cells at concentrations greater than or equal 10(-3) M, the effect being observed after 30 minutes for phascolosomine and after 24 hours for phascoline. At 10(-4) M concentration, the same compounds did not stop the beats but slowed the rhythm after 24 hours of contact. Assays performed with the hydrolysis products of phascoline and phascolosomine, beta-guanidinopropionic acid and 2-hydroxyheptylamine for the former, and beta-guanidinoisobutyric acid and 2-methoxy-n-heptylamine for the latter, have shown that the biological activity is located in the aminoalcool or aminoether moiety of the molelcule. It has been found that the effect on cultured rat heart cells was reversible at concentrations less than or equal 10(-3) M.

Animals

[Electrical activity of cultured cells of the guinea pig heart. Comparison with the rat].

For the first time, action potentials were recorded with the use of microelectrodes from myocardial cells beating spontaneously which were obtained by trypsination of guinea-pig embryonic hearts. 4-5 weeks old embryos have been found most suitable for such experiments. The development of cultures and the recordings obtained were compared to those observed in rat hearts under the same experimental conditions. These results showed that inspite of the known physiological differences between adult rat hearts and adult guinea-pig hearts, the cardiomyoblasts cultured under the same conditions possess common features relating to the repolarization phase of action potential, specially a lack of the plateau.

Action Potentials