Distinctive responses of heart muscle and non-muscle cells to oxygen and glucose deprivation as regards phospholipid fatty acids.
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Animals↗
Biomedical subjects
P Lechat
Publications and source records attributed to P Lechat.
Sodium butyrate-induced changes in cultured rabbit articular chondrocyte transmembrane electrical potentials. Relationship between these changes and the proliferative response.
Sodium butyrate at 5mM reversibly induced a significant increase of transmembrane potentials (Em) in normal chondrocytes (24 hours after seeding) and arrested their proliferation. This increase in Em levels, which could be temporarily abolished by Tetra-ethyl Ammonium (TEA 5mM), was related to an increase in membrane permeability to K+. This hyperpolarization was correlated with the reversible inhibition of growth in G1 induced by the sodium butyrate.
Animals↗
[Echocardiographic study of left ventricular contraction by a scoring method in chronic coronary insufficiency].
The echocardiographic evaluation of left ventricular function in chronic coronary insufficiency is based on the two-dimensional ultrasound examination. Several methods of analysis can be used: volumetric analysis or comparison of the diastolic and systolic contours after separation of the images, but they are relatively difficult to perform and are associated with a certain degree of error. We present the results of a method of analysis based on scoring of the real time image without reprogramming. The left ventricle is divided into nine parts according to Heger's model and the segmental kinetics of each segment are scored according to the following system; 0: parietal aneurysm; 1: dyskinesia; 2: akinesia; 3: hypokinesia; 4: normal. The maximal score is therefore 36. This method was applied prospectively in 30 consecutive patients with chronic coronary insufficiency requiring coronary angiography. The results were compared to those of ventriculography in 30 degrees RAO and 45 degrees LAO cranio-caudal views, which were analysed quantitatively. A correct echocardiographic analysis was obtained in 29 patients. There was good concordance with the ventriculography in 20 cases. In two cases, the contractile abnormality was detected on the echocardiogram, but it was located in an adjacent area on the angiography. In five cases, a localised abnormality of one segment was only detected on angiography. The comparison of the score with the angiographic ejection fraction revealed a good concordance and a very high degree of sensitivity for the method in the identification of cases with an ejection fraction of less than 30 p. cent. This scoring method avoids a number of errors of the other volumetric methods or the methods which compare the contours and it provides clinically significant results.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Energy metabolism of cardiac cell cultures during oxygen deprivation: effects of creatine and arachidonic acid.
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Adenosine Triphosphate↗
Equipotency of anti-curare activity of 4-aminopyridine and 3,4-diaminopyridine in anesthetized rats.
In the curarized preparation, 3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP) were equiactive in their ability to antagonize d-tubocurarine caused complete depression of the indirectly elicited twitches of the sciatic nerve-tibialis anterior muscle preparation in anesthetized rats. In the non-curarized preparation, 3,4-DAP showed 2.3 to 4.0 times stronger augmentation of the indirectly elicited twitches than 4-AP, but both the drugs increased equivalently and slightly the maximally elicited twitches of the chronically denervated muscle. The results suggest that the difference of their prejunctional effects is masked by the postjunctional effects of d-tubocurarine in the indirectly elicited twitches.
4-Aminopyridine↗
[Effect of substances modifying calcium movement on the contractility of cultured cardiac cells].
Cultured cardiac cells from newborn rats were found to be sensitive to the positive or negative inotropic effect of agents capable of interfering with calcium movements. Calcium entry blockers were found specially potent, since diltiazem and nifedipine were still active at concentration of 1 X 10(-9) M. Such a bioassay system seems therefore convenient to compare the relative potency of drugs belonging to this pharmacological class.
Animals↗
[Presynaptic effects of aminopyridines on the neuromuscular junction of vertebrates].
In this review the effects of aminopyridines and chemically related compounds are documented in an attempt to analyse the mechanism underlying their presynaptic actions at the vertebrate neuromuscular junction. Aminopyridines and related compounds are of particular interest because they greatly increase the amount of acetylcholine released in response to both conducted nerve impulses and electrotonic depolarizations of tetrodotoxin blocked motor nerve terminals. The apparent rank order of potency for increasing quantal transmitter release evoked by nerve impulse at physiological pH was as follows: 3,4-diaminopyridine greater than 4-aminopyridine greater than 4-aminoquinoline greater than 3-aminopyridine greater than 2,6-diaminopyridine greater than 2-aminopyridine greater than 4-nitropyridine greater than 4-aminopyridine N-oxyde greater than 4-hydroxypyridine greater than 2,4-dihydroxypyridine. The fact that both pyridine and aniline were found to be inactive indicate that both a pyridine ring and an amino-substituent are necessary for activity. A common site of action for the drugs here reported should be rationalized on the basis that their protonated molecular forms generate a common electrostatic potential field pattern. This results together with those concerning the dependence of pyridine activity on extracellular pH leads to the conclusion that this family of compounds exert its activity at the internal face of the motor nerve terminal membrane. Aminopyridines in concentrations that increase transmitter release evoked by nerve impulses block potassium conductance in motor nerve terminals and lengthen the presynaptic action potential, this effect leads to an enhanced calcium influx and consequently to an increase in acetylcholine release. The fact that aminopyridines had no consistent effect on transmitter release at junctions depolarized by elevated potassium ions strongly supports the view that these drugs have no direct effect on voltage-dependent calcium channels and that their primary site of action is on voltage-sensitive potassium channels of motor nerve terminals.
4-Aminopyridine↗
[Regression of post-infarction parietal dyskinesia after percutaneous coronary angioplasty].
Normalisation of abnormal segmental wall motion is rarely observed after myocardial revascularisation by aorto-coronary bypass when the territory revascularised is the site of post-transmural infarction dyskinesia. In particular, normalisation of segmental wall motion is extremely rare when dynamic tests designed to detect potential for improvement (trinitrin test and post-extrasystolic potentiation) are negative. We present the case of a 41 year old man who had anterior and septal wall dyskinesia 2.5 months after antero-septal infarction which was not improved by trinitrin. Dilatation of the left anterior descending artery by percutaneous coronary angioplasty was undertaken because of recurrent effort angina. Control angiography at 6 months showed almost complete normalisation of left ventricular contraction. This myocardial recovery is paradoxical because the trinitrin test did not show potential for improvement. The case illustrates the possibility of normalisation of segmental abnormalities of left ventricular contraction after revascularisation of the dyskinetic zone by percutaneous coronary angioplasty.
Adult↗
[Effects of injectable nitroglycerin on atheromatous coronary stenoses].
The beneficial effects of glyceryl trinitrate (GTN) are the result of several mechanisms which reduce venous return, cardiac work and intraparietal tension, and redistribute blood flow to the subendocardial layer and ischaemic zones. A direct action on atheromatous coronary stenosis is disputed. The coronary angiogram of 45 patients with organic stenosis and no clinical or electrocardiographic signs of coronary spasm were studied under basal conditions and after intravenous injection of 1.5 mg of GTN. Eighty stenotic segments and the corresponding 80 prestenotic segments were traced for comparison after enlargement on a Vanguard retroprojector and calibrated with reference to the coronary angiographic catheter. Aortic pressure fell 2 minutes after the injection in all patients to return to initial values at the end of the investigation. The diameter of the stenosed segment increased in 17 cases, remained unchanged in 54 cases and decreased in 9 cases. When expressed as a percentage of stenosis, the narrowing increased in 25 cases, decreased in 16 cases and remained the same in 39 cases. In the cases aggravated by GTN the diameter of the stenosis decreased or remained the same, whilst the diameter of the prestenotic decreased; in the cases improved by GTN, the diameters of both stenotic and prestenotic segments increased and prestenotic segments showed only slight variations. There was no difference in the diameter of the prestenotic segments between the 3 groups, but the diameter of the stenotic segments was larger in the group aggravated by GTN in comparison with the other two groups. Different haemodynamic factors and neurotumoral and local metabolic autoregulatory mechanisms may be activated by GTN.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary Angiography↗
The effect of 4'-deoxypyridoxine on rat heart cell cultures under oxygen deficiency.
The purpose of this work was to study the consequences of an intracellular depletion of pyridoxal-phosphate (PLP) in rat heart cells in culture submitted to oxygen deficiency. Glucose (GLc) and 4'-deoxypyridoxine (DOP) effects were separately evaluated after 150 mn of partial oxygen deprivation (N2) with regard to enzyme leakage, beating rates, intracellular concentrations of PLP and the ratio glycogen phosphorylase activity (-5'-AMP/+5'-AMP). PLP concentrations were higher in the air-GLc group than in the air group. alpha-Hydroxybutyrate dehydrogenase (alpha-HBDH) and creatine kinase (CK) leakages were observed in the N2 group, whereas 1.17 +/- 0.17 mM GLc prevented leakage. Beatings stopped in the N2 group, slightly decreased in the N2-GLc group; the ratio (-5'-AMP/+5'--AMP) increased only in the N2 group. With a 1 mM DOP pretreatment a significant decline of PLP was observed either with or without GLc in the culture medium. The ratio (-5'-AMP/+5'-AMP) was lower in the air-DOP group than in the air group, whereas beatings, alph-HBDH and CK activities were identical to the control group. ImM DOP in the N2-DOP group partially prevented alpha-HBDH and CK leakages into the medium but did not prevent the decrease in contractile activity. Surprisingly, PLP concentration increased in the N2-DOP group/air-DOP group and the increase in ratio (-5'-AMP/+5'-AMP) was higher in the N2-DOP group than in the N2 group when compared to the respective control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Thoracic pain precipitated by electric stimulation of the esophagus].
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Adult↗
Evaluation of 4-aminopyridine and 3,4-diaminopyridine penetrability into cerebrospinal fluid in anesthetized rats.
4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) when injected intracisternally to anesthetized rats induced qualitatively similar central nervous system stimulant and convulsant effects at equimolar concentrations. Overall penetrability into cerebrospinal fluid of 4-AP is significantly higher than that of 3,4-DAP after single i.v. administration as evaluated by a high-performance liquid chromatographic determination. The present results can account for the lower central nervous system toxicity of 3,4-DAP when compared to 4-AP previously described after systemic administration.
4-Aminopyridine↗
Determination of glaucine in plasma and urine by high-performance liquid chromatography.
A sensitive method is described for the measurement of d-glaucine in pharmacokinetic studies using only 100-microliter plasma samples or 200-microliter urine samples. It requires a simple extraction clean-up on kieselguhr micro-columns and straight-phase high-performance liquid chromatography with fluorescence detection. Data on selectivity, sensitivity and precision demonstrate the reliability of this method. Its applicability is revealed by single and repeated oral administration pharmacokinetic studies in human subjects.
Administration, Oral↗
Effects of sodium butyrate on growth and cell-cycle kinetics of cultured rabbit articular chondrocytes.
The sodium salt of n-butyric acid was found to inhibit the growth of asynchronous cultures of rabbit articular chondrocytes. This inhibitory effect was dose-dependent between 1 mM and 5 mM, reversible, and accompanied by volume enhancement and modification of cellular morphology. Flow-cytometric analysis showed that drug exposure led to a slowing-down of the cell-cycle progression; after 1 day's exposure, cells accumulated in G1, and after 2 or 3 days' treatment, in G2, without a blockage in M; the increase of cells in G2 was in fact due to an enhancement of binculeated cells. The treated cells had an increased RNA content. Articular chondrocytes seem to be target cells for sodium butyrate and therefore it represents a valuable biological tool for studying the mechanisms of their growth regulation.
Animals↗
Unipolar electrode system for an implantable defibrillator: new experimental approaches.
Defibrillation thresholds are studied in normal dog hearts after induction of ventricular fibrillation by alternating current. Shocks of progressively increasing energies are tried after a period of 10 seconds of sustained ventricular fibrillation. The endocardial electrode system may be either unipolar or bipolar, the distal electrode being situated at the right ventricular apex. The results suggest that for an optimal capacitor in the range of 9-20 uF, unipolar shocks are more effective than bipolar shocks (3-10 versus 10-30 Joules). In addition, several cardiac arrhythmias, including rapid ventricular tachycardia, accelerated idioventricular rhythm, and transient AV block are frequently observed. We conclude that (1) an implantable unipolar endocardial defibrillator seems feasible; and (2) the design should include the appropriate circuits to treat the arrhythmias observed after the shocks.
Animals↗
Effects of D-penicillamine on growth and cell cycle kinetics of cultured rabbit articular chondrocytes.
The long-acting antirheumatic drug D-penicillamine was found to inhibit the growth of asynchronous cultures of rabbit articular chondrocytes. This inhibitory effect was dose-related between 5 X 10(-4) M and 5 X 10(-3) M and was time-dependent for a given dose. Flow cytometric analysis showed that drug exposure led to a slowdown in cell cycle progression. This was manifested as a decrease in the number of cells in S phase, due especially to an accumulation of cells in G0 G1 and also to a slight cessation of cell transit through G2 M. Recovery experiments showed that the effect is transitory and reversible. It is suggested that the articular chondrocyte is a target cell for D-penicillamine and that these cells have a D-penicillamine sensitive restriction point in the G0 G1 phase of the cell cycle and to a less extent in the G2 M phase.
Animals↗
[Indices of partial oxygen deprivation in the culture medium of cardiac cells].
Three indexes of partial oxygen deprivation, i.e. hypoxanthine, alpha HBDH and CK, were investigated in rat heart cell cultures, 7 day-old. Enzyme release in the medium and hypoxanthine uptake by the cells pointed out both oxygen and glucose deprivation, which modelized ischemia. Conversely, hypoxanthine release pointed out oxygen deprivation, in the presence of glucose however, which modelized hypoxia, whereas there was no enzyme leakage in the latter condition.
Anaerobiosis↗
Increase in transmitter release from motor nerve terminals induced by some pyridine derivatives.
The effects of 4-nitropyridine (4-NP), 4-aminopyridine-N-oxide (4-AP-N-O), 4-hydroxypyridine (4-HP), 2,6-diaminopyridine (2,6-DAP), 2,4-dihydroxypyridine (2,4-DHP) and pyridine on isolated sciatic nerve-sartorius muscle preparations were studied by means of intracellular and extracellular recording techniques. In junctions treated with (+) tubocurarine, 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP reversibly increased the amplitude and the latency of end-plate potentials (EPPs) and induced repetitive EPPs in response to single nerve impulses. As shown by extracellular focal recordings, the increase in latency of EPPs was due to a prolongation of the minimum synaptic delay, while the appearance of repetitive EPPs was the result of repetitive firing of motor nerve terminals. 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP increased dose-dependently the quantal content of EPPs, while 2,4-DHP and pyridine were found to be inactive. Comparison of the apparent rank order of potency in increasing quantal transmitter release indicates that the relative activity of the different pyridine derivatives studied is unrelated to their pK values. Spontaneous quantal transmitter release in resting junctions was unaffected by 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP when applied at concentrations that enhanced evoked transmitter release. 4-NP differed from the other pyridine derivatives by producing in high concentrations a time-dependent increase in miniature end-plate potential frequency and a depolarization of the muscle fibres. In addition, 4-AP-N-O, 4-HP and 2,6-DAP were found to have no effect on MEPP frequency accelerated by increasing the external K+ concentration. In conclusion the data presented strongly suggest that 4-NP, 4-HP, 4-AP-N-O and 2,6-DAP facilitate evoked transmitter release from motor nerve terminals by a presynaptic action that seems related to an increased calcium influx secondary to the blockade of potassium channels in the nerve terminal.
Acetylcholine↗