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M Delay

Publications and source records attributed to M Delay.

53 records · Page 3Linked to original sources

Caffeine potentiation of calcium release in frog skeletal muscle fibres.

The effects of caffeine at concentrations up to 3 mM were studied on Ca signals obtained using the metallochromic Ca indicator dyes Arsenazo III and Antipyrylazo III in cut frog skeletal muscle fibres mounted in a triple Vaseline-gap chamber and stimulated by voltage clamp or action potential. The peak amplitude of the transient absorbance change due to Ca2+ release following action potential stimulation is potentiated by an amount dependent on caffeine concentration up to 0.5 mM, and by a concentration-independent amount between 0.5 and 2 mM. At 3 mM-caffeine, the potentiation is reduced, and the Ca signal can have a smaller amplitude than under the control condition. The time course of the rising phase of the Ca signal is preserved by the potentiating effect of caffeine; however, the decay rate of the Ca signal is increasingly slowed at caffeine concentrations greater than 0.5 mM. No substantial change was found in the resting myoplasmic Ca2+ level at caffeine concentrations near 0.5 mM. Even if the free Ca2+ concentration in the presence of this level of caffeine were to increase by 0.04 microM (the threshold of detectability), the calculated potentiation of the Ca signal due to increased partial saturation of intracellular Ca2+ buffers would amount to only about 7%. This value is significantly less than the amount of potentiation observed (up to 40%) following action potentials at caffeine levels of 0.5 mM and above. Experiments made with the impermeant potentiometric dye NK2367 show no alteration by caffeine of the electrical properties of the tubular system. Caffeine at up to moderate concentrations causes a substantial increase in the maximal Ca2+ release obtained following large depolarizations. The voltage dependence of the Ca2+ release is characterized by a caffeine concentration-dependent shift towards more negative membrane potentials. The potentiation of Ca2+ release by caffeine was found to be independent of the external free Ca2+ level. The potentiation of the Ca2+ release process by caffeine is likely to occur at a step subsequent to the depolarization of the transverse tubule membrane, and suggests the presence of an intermediate step, or second messenger, in the excitation-contraction coupling process.

Action Potentials↗

The use of metallochromic Ca indicators in skeletal muscle.

Absorbance signals recorded with metallochromic indicators in skeletal muscle fibers show rapid time courses that probably closely track the fast kinetic process of Ca++ release and retrapping by the sarcoplasmic reticulum. However, the formation of more than one complex in cuvette calibrations, both for Arsenazo III (ArIII) and Antipyrylazo III (ApIII), suggest that care needs to be taken in the deconvolution of in vivo absorbance signals. Since the kinetic rate constants have not yet been obtained for these probes, attempts to deconvolute absorbance signals should be considered approximate. The evidence suggesting that more than one complex is formed during a skeletal muscle transient with ArIII is more compelling than for the case of ApIII. The differences between the ArIII and ApIII signals may not be readily explained assuming 1:1 dye:Ca complexation and kinetic differences between the probes. Competition for Ca++ with cell Ca buffers and/or multiple complex formation by at least one of these probes needs to be invoked. Based on a simple model to simulate the behavior of the Ca signals in muscle, it may be suggested that an ApIII-like probe would more closely track pCa changes in the fiber than would an ArIII-like probe, which would show more interference with intracellular buffers; an even higher affinity probe would tend to sense the total release of Ca by the SR.

Animals↗

Inositol 1,4,5-trisphosphate: a possible chemical link in excitation-contraction coupling in muscle.

The role of inositol 1,4,5-trisphosphate (InsP3) in excitation-contraction coupling in skeletal muscle was investigated by several methods. The following results were obtained. InsP3 is released by electrical stimulation of muscles. Exogenous InsP3 releases calcium from skinned muscle fibers at relatively high doses under normal conditions but does so at very low concentrations when blockers of the InsP3 5-phosphatase are present. Blockers of InsP3 release are effective blockers of calcium transients elicited by electrical stimulation of muscle fibers. It is proposed that InsP3 acts as a chemical second messenger between transverse (T)-tubular membrane depolarization and calcium release from the sarcoplasmic reticulum in skeletal muscle.

Animals↗

[Myocardial infarct of effort with normal coronaries. Study of in vivo platelet activation].

Platelet activation may play a part in causing myocardium infarction with angiographically normal coronary arteries. We investigated this possibility by performing ergometric stress testing in a series of 9 patients (Group A) who had suffered myocardial infarction after a violent effort with angiographically documented coronary insufficiency responsible for a stable effort angina (Group B) and 11 healthy subjects (Group C). Blood samples were taken separately before exercise, at the peak of exercise, and during the recovery period. Platelet morphology, a sensitive indication of the degree of platelet activation, was studied by phase contrast microscopy after immediate fixation of the blood. The percentage of non-discoidal platelets presenting with one or several spicules was measured. At the same time, the plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured. At rest, there was no difference in platelet morphology or specific platelet proteins between the 3 groups. At the peak effort, there was a significant increase of the number of morphologically modified platelets in Groups A and B but not in healthy subjects. This platelet activation could not be linked to the presence of myocardial ischaemia because it was found both in patients with a negative maximal exercise stress test (Group A). Finally, no increase of the plasma concentrations of the platelet protein was observed in any of the groups.

Adult↗

[Prognostic indices of the normalization of left ventricular function in chronic aortic insufficiency following valve replacement].

The aim of this study of 31 patients was to identify M mode echocardiographic parameters predictive of normalisation of left ventricular function after valvular replacement for chronic aortic incompetence in order to determine the optimal time for surgery. Only patients with chronic, pure aortic incompetence (ventriculo-aortic pressure gradient less than or equal to 30 mmHG) were considered. At the time of investigation 4 patients were in functional Class I, 6 in Class II, 10 in Class III and 11 in Class IV (NYHA). M mode echocardiography was performed on an Echovideorex or an Irex System II echocardiograph. The following measurements were made and corrected for body surface area according to the recommendations of the American Society of Echocardiography; end systolic and end diastolic dimensions (mm), fractional shortening (%), end systolic and end diastolic wall thickness (mm), diastolic radius to wall thickness ratio, short axis myocardial surface area (cme), wall stress, end systolic stress (mmHg). The study comprised pre and postoperative studies with an interval of 22.7 +/- 12.5 months (range 5 to 46 months); the data obtained was compared with a control group of 10 normal subjects. The results showed that preoperative fractional shortening less than 28% was associated with an increased risk of persistent postoperative left ventricular dysfunction.

Adolescent↗

[Predictive value of plasma apolipoprotein B in myocardial infarction in young subjects. Correlations with coronarographic data].

In recent epidemiological studies, apolipoprotein-B (apo B), the main low density lipoprotein (LDL), was found to be significantly elevated in patients with early atherosclerosis. The aim of this study was to compare plasma apo B in a population of men who had suffered myocardial infarction before 45 years of age (N = 31) with a control population (N = 22). In the coronary group, there were 27 angiographies between the end of the first and third month. The plasma lipoproteins were separated by ultracentrifugation, cholesterol and triglycerides measured by enzymatic methods and apo B by Laurell's technique of immunoelectrophoresis. Our results showed significantly higher apo B in the coronary group (p less than 0.05). Serum cholesterol, triglycerides, very low density lipoprotein (VLDL) and LDL cholesterol were also significantly higher whilst high density lipoprotein (HDL) cholesterol was significantly lower. In addition, apo B levels correlated with the severity of the coronary lesions on angiography. Therefore, the plasma apo B level is a good predictive indicator of the presence of early coronary atherosclerosis and its severity.

Adult↗

[Systemic fibrinolytic treatment in the acute phase of myocardial infarction. Effects on coronary repermeation and left ventricular function].

Coronary angiography and 2D echocardiography were performed at the 24th hour and 21st day of acute myocardial infarction in 18 patients to study the effects of peripheral fibrinolytic therapy on coronary repermeabilisation and left ventricular function. The treatment was the same for all patients included in the study. The left ventricular ejection fraction and sequential left ventricular contractility were analysed. The first coronary angiographic control study (24th hour) showed coronary repermeabilisation in 18 cases, occurring in significantly stenosed vessels in 15 cases and in angiographically normal vessels in 3 cases, demonstrating appearances of thrombosis. Transluminal coronary angioplasty was performed in 8 cases. Coronary angiography at the 21st day showed 4 secondary occlusions in patients who had not undergone angioplasty. The comparative study of left ventricular function did not show a statistically significant difference between the 24th hour and the 21st day studies. Biochemical studies showed on early massive elevation of the specific myocardial enzyme CPK MB and a rapid fall in the fibrinolytic activity of all patients. The treatment was well tolerated and mortality was nil.

Adult↗

[Coupled use of chromatography and acrylamide-agarose gel electrophoresis in the study of polymeric forms of paraproteins].

A study of the physical properties of paraprotein required until now, the use of fairly complicated techniques, such as analytical ultracentrifugation. The use of chromatography on acrylamide agar pearls and electrophoresis on indubiose plates, coupled with the classical techniques of electrophoresis and immunoelectrophoresis, permitted a more simple approach to these problems. The study of IgA paraproteins in several polymerised forms, is an example of the possibilities of this new method of investigation.

Chromatography↗

[Echocardiographic evaluation of intravenous streptokinase in myocardial infarction in the acute phase].

The effects of intravenous fibrinolysis on left ventricular function in acute myocardial infarction were investigated by two-dimensional echocardiography in patients aged less than 70 for whom fibrinolysis was not contra-indicated and who were admitted less than 6 hours after the onset of a first myocardial infarction without heart failure. The 12 patients thus recruited were male; their mean age was 55 years and the infarct was anterior in 6 cases and posterior in 6 cases. Streptokinase was administered first by bolus intravenous injection (250,000 IU over 20 min), then by intravenous infusion (100,000 IU over 12 hours); this was followed by heparin. No other medication was given, except for intravenous lidocaine and oral nifedipine. Two-dimensional echocardiography was performed after 24 hours and on the 21st day, using the apical, two-cavities projection. The ejection fraction and the percentage of shortening in 16 ventricular segments (8 in the anterior and 8 in the inferior territories) were evaluated from systolic and diastolic ventricular contours. Ventricular angiography and coronary arteriography were performed concomitantly with echocardiography. No significant improvement in ejection fraction was observed. On both day 1 and day 21, the kinetics of the lower segments was improved and that of the anterior segments was distinctly reduced in inferior infarcts. The kinetics of all segments, irrespective of their territory, was significantly improved in anterior infarcts.

Adult↗

Antiarrhythmic drug-induced side effects: a prospective survey of 300 patients.

The purpose of this study was to define the characteristics and the frequency of antiarrhythmic drug-induced side effects. All patients referred for cardiological consultation and treated with antiarrhythmic drugs between April 1992 and October 1993 were prospectively investigated. 300 patients were included in the study: 41 (13.6 per cent) had drug-induced side effects, nine of which were serious: 5 proarrhythmic effects, 1 pulmonary fibrosis, 1 peripheral neuropathy, and 2 acute cardiac failure. Side effects led to discontinuation of treatment in 26 cases (7.6 per cent). Statistical analysis showed that side effects occurred more commonly with disopyramide (46.1 per cent, P < 0.01) or propafenone (41.7 per cent, P < 0.05) and less frequently with sotalol (2 per cent, P < 0.01) than with the other drugs (flecainide 20 per cent; amiodarone 16.4 per cent; cibenzoline 4.8 per cent; hydroquinidine 4.3 per cent). Side effects were more common on bitherapy (39 per cent) than on monotherapy (13 per cent) in general and in the amiodarone-treated group in particular. In conclusion, side effects of antiarrhythmic drugs involved 1/6 patients overall and led to discontinuation of treatment in 1/14. The frequency of proarrhythmias (1.1 per cent) was lower than previously reported, suggesting that recently published clinical trials have modified the prescription habits.

Adolescent↗