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M Courtois

Publications and source records attributed to M Courtois.

28 records · Page 2Linked to original sources

Oxygen and substrate deprivation on isolated rat cardiac myocytes: temporal relationship between electromechanical and biochemical consequences.

The effects of hypoxia and reoxygenation on action potentials (AP), contractions, and certain biochemical parameters were studied in isolated rat ventricular myocytes in monolayer culture in the presence and absence of glucose. Substrate deprivation alone had no influence on the basal properties. In the presence of glucose, a 4-h hypoxic treatment caused only a moderate decrease in AP amplitude and rate. In substrate-free conditions, hypoxia induced a gradual decline in plateau potential level and in AP duration and rate, followed by rhythm abnormalities and a failure of the electromechanical coupling. Spontaneous AP generation then ceased, and the resting potential decreased with increased duration of hypoxia. These alterations were associated with a decrease in ATP content, an increase in the lactate production, and a leakage of about 50% of the total cellular lactate dehydrogenase (LDH). Cells reoxygenated after 150 min hypoxia recovered near-normal function, while the ATP depletion ceased and the rate of lactate and LDH loss was diminished. Conversely, cells reoxygenated after 4 h hypoxia exhibited a further decrease of the residual resting polarization and no change in the decline of intracellular ATP and in the efflux of cytosolic lactate and LDH. The results of this study indicate that (1) the sequence and the extent of functional alterations are dependent on the duration of hypoxia in the absence of exogenous substrate and (2) ATP depletion and the amount of lactate and LDH released during hypoxia are related to the shift from reversibly to irreversibly damaged cells.

Action Potentials↗

Physiological early diastolic intraventricular pressure gradient is lost during acute myocardial ischemia.

A consistent pattern of intraventricular regional pressure gradients exists under physiological conditions during the rapid filling phase of diastole in the normal dog left ventricle. We hypothesized that this pressure gradient pattern is caused, in part, by early diastolic recoil of the left ventricular walls in conjunction with release of elastic potential energy stored during systole, generating suction and thus contributing to diastolic filling. If so, any condition that interferes with normal regional systolic function might be expected to modify the pattern of the normal early diastolic intraventricular pressure gradients. Accordingly, the present study was designed to determine whether acutely induced regional systolic left ventricular mechanical dysfunction is accompanied by changes in the pattern of the early diastolic intraventricular pressure gradients. Acute myocardial ischemia was induced by balloon occlusion of the left anterior descending coronary artery (LAD) in nine anesthetized closed-chest dogs. The maximum early diastolic intraventricular pressure gradient (MIVP) was measured between the mid-left ventricle and apex with a dual-sensor micromanometer (3-cm spacing between the sensors) before and 20 minutes after LAD occlusion. Ejection fraction (EF) and number of dyskinetic chords (DChords) were measured from left ventricular contrast ventriculograms. Twenty minutes after LAD occlusion, the nine dogs evidenced significant changes in EF (56 +/- 10% to 37 +/- 8%), DChords (0 +/- 0 to 17 +/- 16 chords), left ventricular minimum pressure (-1.7 +/- 0.5 to 0.0 +/- 1.5 mm Hg), left ventricular end-diastolic pressure (4.2 +/- 1.2 to 5.9 +/- 2.2 mm Hg), and heart rate (90 +/- 17 to 103 +/- 18 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characterization of regional diastolic pressure gradients in the right ventricle.

Regional intraventricular pressure gradients exist in the left ventricle (LV) during both the early and late filling phases of diastole. These regional pressure gradients comprise a fundamental component of the mechanism of normal LV filling. To determine whether similar diastolic pressure gradients also occur in the right ventricle (RV), we measured right atrial (RA) and RV regional pressures with use of micromanometers in six anesthetized, closed-chest dogs. Tricuspid flow velocity was recorded with use of transesophageal Doppler echocardiography, and right ventriculograms were obtained with contrast angiography. As in the LV, the maximum RA-RV pressure gradient during early diastole was consistently greater if RV pressure was measured near the apex than in the inflow tract (1.6 +/- 0.5 versus 0.8 +/- 0.4 mm Hg). The area of reversed pressure was also found to be significantly greater in the apex than in the inflow tract (72 +/- 43 versus 8 +/- 6 mm Hg.msec). However, unlike the LV, the lowest minimum pressure was usually recorded in the RV outflow tract, resulting in a significantly increased RA-RV outflow tract pressure gradient compared with the RA-RV apex pressure gradient (2.5 +/- 0.8 versus 1.6 +/- 0.5 mm Hg). Analysis of right ventriculograms indicates marked narrowing of the RV outflow tract at end systole in all six animals, suggesting that an end-systolic deformation in this region is the likely mechanism for production of low early diastolic pressure in this region. During atrial contraction the RV regional pressure gradient pattern was similar to the LV pattern: the RV a-wave ascent occurred earlier in the inflow tract and later in the apex. A-wave ascent appeared to occur almost simultaneously in the apex and outflow tract. In the six animals, Doppler-derived peak tricuspid flow velocity during early diastole was 35 +/- 6 cm/sec. Early tricuspid flow acceleration (393 +/- 101 cm/sec2) was found to be significantly greater than deceleration of flow (182 +/- 59 cm/sec2). Comparison of tricuspid pressure-flow data with mitral pressure-flow data previously obtained in our laboratory indicates that the driving pressure gradient across the tricuspid valve is significantly less than across the mitral. This pressure difference corresponds to differences in acceleration and peak flow found across the two valves. Consideration of these physiological patterns of RV diastolic intraventricular pressure and their relation to filling has important implications with regard to the development of indexes that characterize diastolic pressure-flow relations and provides physiological insight relating to the location of ventricular restoring forces.

Animals↗

Modification of the n-6/n-3 fatty acid ratio in the phospholipids of rat ventricular myocytes in culture by the use of synthetic media: functional and biochemical consequences in normoxic and hypoxic conditions.

The respective roles of exogenous polyunsaturated fatty acids on the lipid composition, physiological properties and enzyme release was investigated on isolated cardiac muscle cells in normoxia and hypoxia. Rat neonatal ventricular myocytes were grown for 5 days in conventional serum-supplemented medium. Cells were then incubated for 24 h in fully chemically-defined media featuring a balanced fatty acid composition containing either linoleic acid (18:2 n-6) or linolenic acid (18:3 n-3) as sole polyunsaturated fatty acid source. Transmembrane potentials were monitored with microelectrodes and contractions with a photoelectric device. The radio of n-6 to n-3 phospholipid fatty acids increased from 6.3 in control cells to 20.2 in cells exposed to n-6 fatty acids (SM6) and decreased to 1.4 in those exposed to n-3 fatty acids (SM3). These modifications had no influence on the electrical and mechanical activities and on automaticity in normoxic conditions. The action potential depression under hypoxia was less severe in SM6 cells, whereas there was a better electrophysiological recovery upon reoxygenation in SM3 cells. However, the loss of lactate dehydrogenase during sustained hypoxic treatment was not affected by changes in phospholipid fatty acid pattern. These results suggest that the effect of the polyunsaturated fatty acid balance depends on the cellular function under study and on the environmental conditions.

Animals↗

Transmitral pressure-flow velocity relation. Importance of regional pressure gradients in the left ventricle during diastole.

Effects of regional diastolic pressure differences within the left ventricle on the measured transmitral pressure-flow relation were determined by simultaneous micromanometric left atrial (LAP) and left ventricular pressure (LVP) measurements, and Doppler echocardiograms in 11 anesthetized, closed-chest dogs. Intraventricular pressure recordings at sites that were 2, 4, and 6 cm from the apex were obtained. Profound differences between these sites were noted in the transmitral pressure relation during early (preatrial) diastolic filling. In measurements from apex to base, minimum LVP increased (1.6 +/- 0.7 to 3.1 +/- 0.8 mm Hg, mean +/- SD); the time interval between the first crossover of transmitral pressures and minimum LVP increased (31 +/- 3 to 50 +/- 17 msec); the slope of the rapid-filling LVP wave decreased (74 +/- 13 to 26 +/- 5 mm Hg/sec); the maximum forward (i.e., LAP greater than LVP) transmitral pressure gradient decreased (3.6 +/- 1.3 to 2.1 +/- 0.7 mm Hg); the time interval between the first and second points of transmitral pressure crossover increased (71 +/- 9 to 96 +/- 13 msec); and the area of reversed (i.e., LVP greater than LAP) gradient between the second and third points of transmitral pressure crossover decreased (101 +/- 41 to 40 +/- 33 mm Hg.msec). During atrial contraction, significant regional ventricular apex-to-base gradients were also noted. The slope of the LV A wave decreased (26 +/- 10 to 16 +/- 4 mm Hg/sec); LV end-diastolic pressure decreased (8.1 +/- 2.0 to 7.4 +/- 2.0 mm Hg), and the upstroke of the LV A wave near the base was recorded earlier than near the apex. All differences were significant at the 0.05 level. Simultaneous transmitral Doppler velocity profiles and transmitral pressures were measured at the 4-cm intraventricular site. The average interval between the first and second points of pressure crossover and between the onset of early rapid filling and maximum E-wave velocity were statistically similar (81 +/- 13 vs. 85 +/- 12 msec; NS); and the average area of the forward transmitral pressure gradient associated with acceleration of early flow was significantly greater than the area of reversed gradient associated with deceleration of early flow (133 +/- 36 vs. 80 +/- 46 msec.mm Hg; p less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)

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The transmitral pressure-flow velocity relation. Effect of abrupt preload reduction.

Although recent animal and clinical studies suggest that Doppler-derived indexes may be useful for the characterization of ventricular diastolic behavior, the hemodynamic basis for the preload dependency of these indexes has not previously been fully elucidated. Accordingly, effects of reduction of left atrial load on the pressure-flow velocity relation were characterized in 10 anesthetized, closed-chest dogs during transient inferior vena caval occlusion by means of simultaneously recorded left atrial and left ventricular micromanometric pressure measurement and transesophageal Doppler echocardiograms. Within four or five beats after inferior vena caval balloon occlusion, left atrial loading was reduced as evidenced by a decrease in the slope of the left atrial v wave from 21 +/- 4 to 13 +/- 4 mm Hg/sec (p less than 0.001) and by a decrease in the first crossover point of left atrial and left ventricular pressures from 5.6 +/- 1.1 to 2.9 +/- 1.5 mm Hg (p less than 0.001). This decrease in left atrial loading resulted in reductions during early diastole of minimum left ventricular pressure (from 1.0 +/- 0.8 to -0.4 +/- 1.2 mm Hg, p less than 0.001), the maximum early forward (i.e., left atrial pressure greater than left ventricular pressure) transmitral pressure gradient (from 2.8 +/- 0.8 to 2.4 +/- 0.5 mm Hg, p less than 0.01); the slope of the rapid filling pressure wave (from 44 +/- 11 to 38 +/- 10 mm Hg/sec, p less than 0.025); and the area of the reversed (i.e., left ventricular pressure greater than left atrial pressure) transmitral pressure gradient (from 79 +/- 42 to 53 +/- 33 mm Hg.msec, p less than 0.05). During late diastole, both the heights and slopes of the left atrial and left ventricular a waves fell, resulting in a decrease in the maximum late transmitral pressure gradient (from 1.2 +/- 0.7 to 0.9 +/- 0.5 mm Hg, p less than 0.05). Vena caval occlusion also altered Doppler transmitral velocity profiles during both the early and late phases of diastole. Peak velocity of the E wave decreased (from 50 +/- 11 to 41 +/- 7 cm/sec, p less than 0.01) as did acceleration (from 880 +/- 222 to 757 +/- 258 cm/sec2, p less than 0.025) and deceleration (from 597 +/- 260 to 429 +/- 197 cm/sec2, p less than 0.025). Peak velocity of the A wave also fell (from 29 +/- 9 to 22 +/- 5 cm/sec, p less than 0.005). Abrupt inferior vena caval occlusion did not significantly change heart rate or mean aortic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

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A simple gas-flow chamber for cultured cell electrophysiology in a controlled atmosphere.

A simple and inexpensive device is described to control the gaseous environment while recording membrane potentials and contractile motion from single cultured cells. This equipment was used to study the electrophysiological and mechanical responses to hypoxia of cultured rat heart cells, but should also be suitable for a wide range of applications with several cell types.

Action Potentials↗

Prenatal development of mouse central nervous structures: time of neuron origin and gradients of neuronal production. A radioautographic study.

In order to obtain an overall view of neurogenesis in the main central nervous structures of the mouse, we have undertaken a systematic study of the time of neuron origin and of the gradients of neuronal production. The animals were the offspring of pregnant females given a pulse label of 3H-thymidine on selected days after conception. These days were chosen to cover the principal brain development stages: E10.5, E11.5, E12.5, E13.5, E14.5, E15.5, E16.5, E17.5 and E18.5. The offspring were sacrificed during the fourth postnatal week and labeling indices were calculated in the different brain structures. The study of labeling indices as a function of the day of injection and of the brain level studied provided us with information on the major periods of neuronal proliferation in these structures and allowed us to analyse the formation gradients inside a given nervous structure. As a whole, for a majority of nervous structures (olfactory, cortical, septal, hippocampal, preoptic, thalamic, epithalamic, hypothalamic and cerebellar structures), our results are in good agreement with the already published observations. However, we outlined two major phenomena apparently unobserved until now in the mouse: the first is a rostrocaudal gradient of neuronal production in the inferior colliculi, and the second is the long period of neuronal proliferation in the caudate nucleus lasting from E11.5 to E18.5, along a complex inside-out and mediolateral gradient.

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