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Biomedical subjects

J F Prost

Publications and source records attributed to J F Prost.

50 records · Page 3Linked to original sources
PubMed1986

Choosing the right dose for beta-blocker treatment of hypertension: experience with tertatolol.

The determination of the optimum dosage for antihypertensive therapy, i.e. the unit dose and the administration frequency, remains one of the least discussed subjects. For beta-blockers as well as for other drugs, this determination is mainly based on the dose-effectiveness curve, the top of which corresponds to the right dose. Thus, a wide range of doses should be tested, and this as early as possible during drug development. The first step is to assess the optimum beta-blocking dose in healthy volunteers during phase I studies. These dose-response studies are usually performed according to a cross-over design. Among the many techniques proposed for assessing the effects of beta-blockers in man, isoprenaline and dynamic exercise tests are the most commonly used. The second step is to make use of the previous results to find the right dose for hypertensive patients in phase II studies. However, many individual factors which can influence the blood pressure response should be kept in mind, especially the initial blood pressure level. The choice of the design is generally based on the need to have repeated administration in order to obtain optimum control of the hypertension. Therefore, the cross-over design, although theoretically the best one, is rarely used on account of its practical and ethical problems. In contrast, the parallel design, with random assignment of treatments, is suitable to most experimental situations. Very different in nature, the stepped dose design stems from an ethical and practical approach of dose finding and thus is also widely used. Finally, correct measurement techniques of blood pressure are required.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Cardiopulmonary effects of a single oral dose of almitrine at rest and on exercise in patients with hypoxic chronic airflow obstruction.

Almitrine, a new triazine derivative, was studied in a double-blind, randomized, parallel study in 16 patients with hypoxic chronic airflow obstruction (eight almitrine and eight placebo). At rest, compared to placebo, a 3 mg/kg single dose of almitrine given orally significantly increased the partial pressure of oxygen (mean increase: +12.0 +/- SEM 2.1 mm Hg, p less than 0.001) and decreased the partial pressure of carbon dioxide (mean decrease: -6.0 +/- 0.7 mm Hg, p less than 0.001); this improvement in arterial blood gases persisted on exercise. The lack of significant change in ventilation and the decrease in the alveolar-arterial oxygen gradient (mean decrease -10.0 +/- 1.9 mm Hg; p less than 0.001) at rest suggests a change in the distribution of the ventilation-perfusion ratio in the lung; such a change was confirmed by a krypton 81m isotopic study. Pulmonary hemodynamic responses were studied at rest and on exercise; a significant but slight increase in mean pulmonary artery pressure at rest (+4.0 +/- 1.5 mm Hg, p less than 0.05) was found.

Administration, Oral↗
PubMed1984

[Evaluation of the severity of pulmonary embolism. Value of the measurement of stable carbon monoxide transfer capacity].

A non-invasive and easily repeatable method of pulmonary gas exchange evaluation, using measurements of stable carbon monoxide transfer capacity (DLCO) and alveolar-capillary ductance ( DuaCo ), was compared to a complex, invasive method of pulmonary vascular bed evaluation (pulmonary angiography) in 17 patients during the first 24 hours of pulmonary embolism. DLCO and DuaCo measurements were subsequently repeated in several of the patients during the course of the disease. The study showed that DLCO was lowered in both massive (Walsh's angiographic index 12.9 +/- 1.9) and submassive (Walsh's index 4.1 +/- 1.3) pulmonary embolism, with values of 7.0 +/- 2.5 and 7.0 +/- 1.8 ml/min/mm Hg respectively. It also showed a highly significant correlation between the degree of vascular obstruction, as determined by Walsh's angiographic index, and the reduction of alveolar-capillary gas exchange, as evaluated by DuaCo (r = 0.80; p less than 0.001). A progressive improvement in the pulmonary capillary bed perfused could be suspected from the results of DuaCo monitoring during the course of embolism.

Carbon Monoxide↗
PubMed1984

Echocardiographic evaluation of ventricles during continuous positive airway pressure breathing.

Using M-mode and two-dimensional echocardiography, we have compared left and right ventricular dimensions at expiration and inspiration in a group of 12 healthy young volunteers during the following two distinct periods: 1) a control period with atmospheric pressure breathing, and 2) a continuous positive airway pressure (CPAP) period with 15 cmH2O end-expiratory pressure breathing. In 6 of the 12 subjects we also evaluated inferior vena caval size, using the same technique. Inspiratory decrease in left ventricular short-axis area (A), length (L), calculated volumes (V = 5/6 AL), and inspiratory increase in right ventricular short-axis diameter and long-axis area were evident at both control and CPAP periods. CPAP also produced a marked decrease in left and an increase in right ventricular dimensions during both expiration and inspiration and a significant decrease in calculated stroke output. An increase in vena caval size during CPAP breathing indirectly suggested a decrease in venous return, but the finding of an unchanged percent of inspiratory change of this vessel during CPAP indicated that the inspiratory augmentation of venous return was still present. On the other hand, the finding of an increased right ventricular size indicated that the right ventricle was afterloaded by CPAP; this probably could explain the observed reduction in calculated stroke output.

Adult↗
PubMed1984

Two-dimensional echocardiographic assessment of left ventricular function in chronic obstructive pulmonary disease.

In 10 patients undergoing therapy for a mild exacerbation of their chronic obstructive pulmonary disease (COPD), a quantitative two-dimensional echocardiographic (2DE) study was performed together with hemodynamics to assess left ventricular (LV) function. From the 2DE examination, which was made up of parasternal, subcostal, and apical views, measurements of LV short axis end-diastolic and end-systolic areas (A) at the high papillary muscle level and long axis end-diastolic and end-systolic length (L) permitted us to calculate LV end-systolic and end-diastolic volumes (V) using the formula V = 5/6 AL. Compared with the same measurements obtained in a group of 12 normal volunteers, patients with COPD exhibited a markedly reduced LV cavity (LVES, 28.9 +/- 14.6 ml/m2 versus 51.5 +/- 11.0 ml/m2; LVEDV, 67.7 +/- 24.6 ml/m2 versus 103.2 +/- 19.9 ml/m2). An increased thickness of both left ventricular free wall and interventricular septum was also evidenced in patients with COPD. Left ventricular systolic function, assessed using both peak systolic blood pressure/end-systolic volume ratio and calculated left ventricular ejection fraction, was found to be clearly enhanced in patients with COPD. The influence of right ventricular enlargement on left ventricular diastolic function was also investigated in patients with COPD using progressive volume loading and 2DE right ventricular measurements. After a given threshold of volume loading, reduction in stroke index, opposite variations in right and left ventricular size and septal flattening, suggested the occurrence of ventricular interaction.

Adult↗
PubMed1982

[Outcome of the adult acute respiratory distress syndrome. Predictive value of a severity index calculated from arterial oxygenation (author's transl)].

A retrospective study was carried out a group of 50 adult patients who had presented with acute respiratory distress syndrome and had all been treated by mechanically controlled ventilation with positive end-expiratory pressure (PEEP). The predictive value of the so-called "severity index" was tested. This index, which is used from the second day of treatment onward to predict with strong probability whether the lung lesions will subside or develop, is obtained from the PaO2 after corrections taking into account the FiO2 and the PEEP level. The study also supplied information on the outcome of lung lesions which may result in one of four possible courses of about equal frequency: the patient may either die or be cured rapidly after less than a week of assisted ventilation, or he may die at a later date or be cured slowly after more than a week of assisted ventilation.

Female↗
PubMed1982

Mechanism of paradoxic pulse in bronchial asthma.

To elucidate the mechanism of paradoxic pulse in severe bronchial asthma, we performed hemodynamic studies and measured esophageal pressure in nine patients who had status asthmaticus and clinical paradoxic pulse. Two-dimensional echocardiography allowed simultaneous assessment of cyclic changes in right- and left-heart size throughout the respiratory cycle. Esophageal pressure varied from a markedly negative level during inspiration (-24.4 +/- 6.5 cm H2O) to a positive level during expiration (7.6 +/- 6.0 cm H2O). Competition between right- and left-heart chambers for pericardial space during inspiration was suggested by the reduced left ventricular cross-sectional area at end-systole (-24%, p less than 0.01) and end-diastole (-32%, p less than 0.01), the leftward septal shift, and the increased right ventricular internal diameter at end-systole (42%, p less than 0.01) and end-diastole (40%, p less than 0.001). Competition for filling, however, could not entirely account for the paradoxic pulse, for systemic and pulmonary pulse pressures were almost (within one cardiac cycle) in phase: both were minimal at inspiration and maximal at expiration. The increase in impedance to right ventricular ejection is another major factor reducing left ventricular preload at inspiration. This reduction in preload was shown to be the predominant mechanism for the decrease in left ventricular stroke output at inspiration.

Adult↗
PubMed1982

Hemodialysis in septic patients: improvements in tolerance of fluid removal with concentrated albumin as the priming fluid.

Hemodynamic function and volume of ultrafiltration (UF) during hemodialysis were studied in 8 patients with anuric acute renal failure (ARF) and severe sepsis. Patients were alternatively dialyzed with a saline priming (every 2 days) and with a 17.5% albumin priming. Hypovolemia, as indirectly reflected by reduced left ventricular filling pressure, decreased cardiac output (CO), and decline in mean systemic arterial pressure (MAP), was observed during the hemodialysis procedure using saline as the first prime. Hemodialysis was tolerated better after concentrated albumin priming; left ventricular filling pressure increased during the 1st h of dialysis, whereas CO and MAP remained close to that of control values. Furthermore, UF could be increased progressively without major hemodynamic consequences in the patients who received a concentrated albumin priming; moreover, larger volumes of fluid were removed.

Acute Kidney Injury↗
PubMedDate not supplied

Cardiovascular and renal effects of the beta-blocker SE2395 in conscious normotensive dogs.

The cardiac and renal hemodynamic effects of SE2395, a beta-blocking agent, were examined after intravenous administration (50 micrograms/kg) in normotensive conscious dogs. Beta-blocking action of SE2395 was evidenced by a reduction in heart rate and cardiac output without change in the mean arterial pressure. An increase in glomerular filtration rate (inulin clearance) and a slight enhancement in effective renal plasma flow (para-aminohippurate clearance) were observed without attendant decreases in plasma renin activity. An increase in urinary sodium excretion was also observed; urinary prostaglandin E2 excretion was, however, unchanged. We conclude that at effective beta-blocking dosage SE2395 does not induce any detrimental effect on renal function in conscious dogs.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Prejunctional beta-adrenoceptors in the isolated perfused rat kidney: a comparative study of the beta-blockers tertatolol and propranolol.

The interaction of the beta-blocker tertatolol with the prejunctional beta-adrenoceptors of the rat renal vasculature was examined. In isolated Tyrode-perfused rat kidneys isoproterenol (5 x 10(-7) M to 2 x 10(-6) M) slightly decreased the pressor responses to noradrenaline (0.5 nmol), but markedly increased those to electrical stimulation (6 Hz). Tertatolol at 3 x 10(-7) M inhibited both effects of isoproterenol. Electrical stimulation (6 Hz) caused an overflow of intact 3H-noradrenaline from kidneys previously labelled with the 3H-transmitter; this stimulation-induced release was augmented by isoproterenol. Also this effect of isoproterenol was prevented by 3 x 10(-7) M of tertatolol. In different groups of rat kidneys labelled with 3H-noradrenaline, isoproterenol (5 x 10(-7) M) augmented the stimulation (1 Hz), induced 3H overflow and this increased transmitter output was concentration-dependently inhibited by tertatolol and propranolol; from the IC50 values it was calculated that tertatolol was 16 times more potent than propranolol. Even at concentrations up to 10(-5) M, neither tertatolol nor propranolol significantly altered the basal and stimulation-induced transmitter release from the rat kidneys. From the data we conclude that tertatolol is a powerful inhibitor of the prejunctional beta-adrenoceptors in the renal circulation of the rat. Stimulation of these receptors by beta-agonists not only enhances transmitter release but also increases the pressor responses induced by electrical stimulation.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Computer technic for measurement of the pulmonary transfer of carbon monoxide].

An informatic method is described for accurate on-line computation and recording of pulmonary transfer for carbon monoxide (steady state CO uptake with alveolar CO measured from end-tidal determination of gas) using fast response transducers for ventilatory flow and carbon monoxide tension. Special procedures for time alignement of flow and tension signal, and for determination of PACO by microcomputer, are described. The accuracy of the method was studied under informatic and non informatic methods PECO, PACO and TLCO values are in good agreement with those obtained by the conventional non-informatic method.

Carbon Monoxide↗