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Biomedical subjects

J L Cuche

Publications and source records attributed to J L Cuche.

At least 37 records · Page 2Linked to original sources
PubMed1993

Twenty four hours head-down tilt decreases arterial baroreflex function in conscious rat.

In human zero gravity induces a cardiovascular deconditioning. The transfer of blood from the periphery to the thoracic compartment, occuring immediately at the beginning of the exposure to microgravity seems to be involved in this phenomenon. We have previously shown that LBNP (-40 mm Hg) produced an exaggerated heart rate response at the end of 24 hours of bed rest without modification of the cardiopulmonary receptors in human. Some other studies have shown that microgravity induces an impairment of the baroreflex sensitivity in human, but its involvement in the cardiovascular deconditioning is not completely understood. The aim of this study was to determine the modification of the arterial baroreflex using a model of simulated weightlessness in conscious rats during the exposure to microgravity.

Animals↗
PubMed1992

Carotid arterial haemodynamics after mild degrees of lower-body negative pressure in man.

1. Pulsatile changes in the diameter of the common carotid artery were studied transcutaneously using an echo-tracking technique in 15 normal subjects: eight subjects before and during application of graded lower-body negative pressure from -5 to -15 mmHg, and seven subjects before and during weight-bearing head-up tilt at 30 and 60 degrees. 2. In concomitant studies of changes in forearm vascular resistance, it was seen that mild lower-body negative pressure produced deactivation of cardiopulmonary receptors without changes in systemic blood pressure or heart rate. 3. After lower-body negative pressure, a significant decrease in carotid arterial diastolic diameter [from 0.662 +/- 0.028 to 0.624 +/- 0.033 cm (lower-body negative pressure -10 mmHg) and 0.640 +/- 0.030 cm lower-body negative pressure -15 mmHg), P < 0.001 and < 0.05] was observed. 4. After head-up tilt, carotid arterial diameter was also significantly decreased at 30 and 60 degrees, whereas a significant increase in heart rate occurred only at 60 degrees and mean blood pressure did not change. 5. The study provides evidence that the geometry of the arterial wall is substantially modified by non-invasive manoeuvres such as head-up tilting and lower-body negative pressure. The latter is assumed to selectively deactivate human cardiopulmonary receptors, but the present data suggest that local changes may also influence carotid baroreceptors.

Adult↗
PubMed1992

Arterial effects of salt restriction in hypertensive patients. A 9-week, randomized, double-blind, crossover study.

OBJECTIVE: To investigate the hemodynamic effects of a moderately low-salt diet in a 9-week, randomized, double-blind, crossover study in 20 hypertensive, ambulatory patients. METHODS: All subjects followed a 9-week, low-salt diet. During this period, they received capsules containing either lactose or salt in 4-week treatment periods, separated by a 1-week washout period. Hemodynamic and biological parameters were evaluated on the day of randomization and at the end of weeks 4 and 9. We defined a low-sodium diet (LSD) as a salt-restriction period with lactose capsules, and a normal-sodium diet (NSD) as a salt-restriction period with capsular salt supplementation. RESULTS: Blood pressure was significantly lower during LSD compared with NSD. This fall in blood pressure was associated with a decrease in peripheral resistance in carotid and forearm circulation. Brachial artery diameter was larger during LSD whereas carotid artery diameter remained unchanged. The changes in brachial artery were: (1) not related to blood pressure changes; (2) positively related to age, and (3) negatively correlated with baseline intracellular sodium content. CONCLUSIONS: These results suggest that moderate low-salt restriction is capable of decreasing blood pressure and peripheral resistance in carotid and forearm circulation. The increase in brachial, but not carotid, artery diameter following salt restriction suggests a difference in salt dependence among different arteries.

Adult↗
PubMed1992

Potential role of the renal tubule in fixing the level of plasma sulfoconjugated catecholamines in the dog.

Plasma levels of sulfoconjugated catecholamines in human subjects and in dogs are usually much higher than those of native amines. Their origins and the mechanism(s) involved in fixing their plasma concentrations are not well known; however, several lines of clinical evidences indicate a major role for the kidney. Thus this study was undertaken to measure the renal fractional excretion--used as an overall index of kidney mechanisms involved in the handling of catecholamines and their sulfoconjugates in the dog--and to look for any possible relationships between plasma concentration and urinary excretion. This was carried out in 36 anesthetized hydropenic mongrel dogs. The mean values of the renal fractional excretion of sulfoconjugated dopamine, norepinephrine, and epinephrine were shown to be statistically greater than 100%, suggesting a predominant secretion by the renal tubules of hydropenic dogs. Statistically significant correlations between plasma concentration and urinary excretion of sulfoconjugates--independent of blood pressure, cardiac output, clearance of para-aminohippuric acid, glomerular filtration rate, and sodium excretion are reported. Thus any change in the tubular handling of sulfoconjugates is likely to have a direct consequence in the fixation of their plasma concentrations.

Animals↗
PubMed1991

Oral pharmacokinetics of bisoprolol in resting and exercising healthy volunteers.

The effects of exercise on bisoprolol oral pharmacokinetics were studied in eight healthy male volunteers in an open, randomized, three-period, crossover trial. Oral bisoprolol (20 mg) was given either at rest during 24 h or with iterative stress tests before and 2.5, 5, 10, and 24 h after dosing. Exercise tests were repeated on a third placebo period. Bisoprolol was assayed in plasma and urines, and plasma catecholamines were measured before and after stress tests, Cmax, Tmax, elimination t1/2, and renal clearance of bisoprolol were not significantly modified by exercise. AUC0-infinity significantly decreased by 7.5% (p less than 0.05) with stress test resulting in an increase in apparent oral clearance. The beta-blocking effect peaked at 2.5 h, lasted greater than 24 h, and was related to plasma levels. The exercise-induced increase in plasma norepinephrine levels was significantly augmented with bisoprolol. These results suggest that repeated exercise tests exerted only limited effects on the oral pharmacokinetics of bisoprolol.

Adrenergic beta-Antagonists↗
PubMed1991

Twenty-four hours of bed rest with head-down tilt: venous and arteriolar changes of limbs.

The hemodynamic changes after 24 h of bed rest with -5 degree head-down tilt were studied in six normal subjects as a condition causing an intrathoracic shift of blood volume with a resulting urinary sodium and water loss and a subsequent reduction in total intravascular volume. Vascular resistance and venous tone of the upper and the lower limbs were investigated as were systemic hemodynamics throughout the procedure. Whereas systemic hemodynamic parameters did not change significantly, vascular resistance and venous tone of the upper and lower limbs decreased significantly up to the sixth h and then returned toward baseline values at 24 h. Systemic and forearm vasoconstriction responses to lower body negative pressure (LBNP) were studied just before and at the end of the study period. With LBNP, -5, -10, and -15 mmHg pressure levels were used to investigate mechanoreceptors in the low-pressure system, whereas the -40 mmHg pressure level was used to explore baroreceptors both in low and high pressure systems. Changes in vascular resistance in response to LBNP did not differ at the beginning and at the end of the head-down tilt, whereas an exaggerated heart rate response was observed at -40 mmHg at the end of 24 h of bed rest. The study showed that after 24 h of bed rest with -5 degree head-down tilt, the adaptative changes in venous tone and vascular resistance to blood volume reduction were altered. A dissociation between cardiac and vascular baroreflex response was observed in situations simulating tilting.

Adult↗
PubMed1990

Effects of restraint stress on catecholamine concentrations in the glandular stomach of rats.

Restraint stress is known to induce gastric ulcers in rats. Peripheral sympathetic activity and catecholamines are involved in the pathogenesis of these gastric ulcers. The aim of the present study was to evaluate the effects of restraint on mucosal and muscle catecholamine concentrations in the glandular stomach of rats. In unrestrained rats, noradrenaline concentration was higher in the muscle than in the mucosa of the glandular stomach (629 +/- 106 vs 18 +/- 3 pg/mg and 217 +/- 37 vs 18 +/- 8 pg/mg, respectively in the corpus and the antrum, p less than 0.01). This can be explained by the existence of an abundant noradrenergic innervation in the muscle layer. After 20 hours of restraint, adrenaline and noradrenaline concentrations were significantly decreased in adrenals, in comparison with unrestrained animals (255 +/- 53 vs 638 +/- 160 ng/mg and 113 +/- 17 vs 198 +/- 37 ng/mg, respectively for adrenaline and noradrenaline, p less than 0.05). In the glandular stomach, noradrenaline and adrenaline concentrations in restrained rats were not significantly different from those in unrestrained rats. However, adrenaline concentrations in the muscle of restrained rats were higher than in the mucosa. Moreover, restraint induced a significant decrease in dopamine concentration in the antral mucosa (from 100 +/- 12 pg/mg in unrestrained rats to 15 +/- 5 pg/mg in restrained rats), suggesting that a depletion in dopamine in the antral mucosa could be one of the pathogenetic factors involved in antral gastric stress-induced ulcers in rats.

Animals↗
PubMed1990

Physical properties of the aorta and cardiac hypertrophy in essential hypertension.

The load of the heart in hypertension is related not only to increased peripheral vascular resistance but also to decreased aortic compliance. From non-invasive clinical studies involving determinations of pulse wave velocity and systolic-diastolic variations of aortic arch diameter, it can be shown that decreased aortic compliance is strongly related to increased cardiac mass. The correlation is observed even after adjustment for the level of blood pressure. It is suggested that decreased aortic compliance in hypertension causes a disproportionate increase in systolic pressure and end-systolic stress, thus contributing to promote cardiac hypertrophy with possible consequences for epidemiology, clinical investigation and treatment.

Aorta, Thoracic↗
PubMed1990

Influence of diuretics on brachial artery diameter and distensibility in hypertensive patients.

Blood pressure, brachial artery diameter and pulse wave velocity were determined before and after diuretic treatment in 2 groups of hypertensive patients treated either by indapamide (2.5 mg per d) or by canreonate (50 mg per d). Brachial artery diameter, measured from pulsed Doppler flowmetry, and pulse wave velocity, evaluated from mechanography, did not alter significantly despite a significant blood pressure reduction. The study indicates that, in hypertensive patients of middle age, diuretics did not change brachial artery diameter and distensibility, whether the drug caused an increase or a decrease in plasma potassium levels.

Adult↗
PubMed1990

Conjugated catecholamines in human plasma: where are they coming from?

The origins of conjugated catecholamines remain poorly known. The aim of the present study was to see whether a major contribution comes from the sympathetic nervous system. We have assumed some kind of parallelism between the activity of the sympathetic nervous system, the amount of catecholamines released and taken up, and the amount of conjugated catecholamines circulating in plasma. Accordingly, an increase in sympathetic activity should be followed by an increase in the plasma level of conjugated catecholamines. The plasma levels of sulfoconjugated and glucuroconjugated catecholamines were measured in 10 patients with mental disease resistant to drug treatment, before and after electroconvulsive therapy. As expected, blood pressure, norepinephrine concentration, and epinephrine concentration in plasma were transiently increased. Neither sulfoconjugated nor glucuroconjugated catecholamines were significantly changed. Conjugated catecholamines were measured in 10 volunteers before and at the nadir of insulin-induced hypoglycemia. As expected, plasma levels of norepinephrine and epinephrine were drastically increased. Plasma levels of sulfoconjugates were decreased and glucuroconjugates increased; these were narrow but statistically significant variations. Data reported in the present article do not support a major role for the activity of the sympathetic system in fixing the level of conjugated catecholamines in human plasma. This is a negative, but nonetheless important, observation. In human subjects, currently available information suggests an important role for the intestinal wall and renal function in determining the level of circulating sulfoconjugates.

Blood Glucose↗
PubMed1990

Free and conjugated catecholamines in patients with cirrhosis.

A defect of conjugation may play a role in the elevated plasma free norepinephrine observed in patients with cirrhosis. Plasma free, sulfoconjugated, and glucuronoconjugated catecholamine concentrations were assessed in 15 patients with cirrhosis and in 15 age-matched control subjects. Plasma free norepinephrine and epinephrine levels were significantly higher in patients with cirrhosis (481 +/- 75 and 96 +/- 16 pg/ml, respectively) than in those of the control group (307 +/- 33 and 42 +/- 10 pg/ml, p less than 0.05 and p less than 0.01, respectively). Plasma free dopamine levels were similar in both groups. Sulfoconjugated catecholamines were the predominant form in plasma from both cirrhotic patients and control subjects. The ratio of conjugated to total catecholamines was similar in the two groups. Therefore, it is unlikely that a defect in conjugation of catecholamines is contributing to the excessive plasma free norepinephrine and epinephrine concentrations found in patients with cirrhosis. Moreover, in patients with cirrhosis, no significant relation was found between plasma conjugated catecholamines and the severity of liver disease. This study shows that cirrhosis does not induce alteration in conjugation of catecholamines and that hepatocellular function is not essential for conjugation of circulating catecholamines.

Adult↗
PubMed1989

[Plasma noradrenaline. Significance and practical value of its determination].

The noradrenaline (NA) that has diffused from sympathetic synapses into plasma can be assayed accurately and reliably in plasma, as it is the best index of sympathetic activity. A considerable advance has been achieved by using infusions of tritium-labelled exogenous NA, such infusions being devoid of functional effect. By measuring simultaneously blood NA levels and circulating tritiated NA levels the amplitude of synaptic spillover and therefore of sympathetic activity can be evaluated and the metabolic NA clearance can be measured. Synaptic NA spillover and NA metabolic clearance were measured in 24 physiological, pathological and pharmacological situations, providing an accurate definition of the sympathetic states explored. By combining these techniques with selective vascular catheterization, the sympathetic activity of the organs explored can be assessed, and regional sympathetic activities are currently being mapped. Such regional studies are of great value to understand the mechanisms involved in heart failure, cirrhosis or arterial hypertension. Sympathetic system regulations result from a central influence and from peripheral adjustments that are potentially specific to each organ.

Humans↗
PubMed1989

Portal and arterial free and conjugated noradrenaline in two models of portal hypertension in rats.

Free and conjugated noradrenaline concentrations were measured in portal-venous and arterial plasma from sham-operated rats or rats with portal hypertension. Two types of portal hypertension in rats were evaluated: in portal vein stenosed rats, the liver was normal, whereas cirrhosis developed in bile duct ligated rats. In cirrhotic rats, arterial free noradrenaline level was higher than in both sham-operated and portal-stenosed rats, this indicating that enhanced sympathetic nervous activity depends on the development of cirrhosis. In all groups of rats, portal venous plasma free noradrenaline was higher than arterial plasma level, indicating a production of noradrenaline by splanchnic organs. Arterial noradrenaline level may be mainly dependent on this splanchnic production in case of portal hypertension. Sulfoconjugated and glucuronoconjugated noradrenaline plasma levels were similar in the three groups of rats. This shows that alteration in conjugation is not likely to be a major factor in the abnormal circulating levels of free noradrenaline observed in cirrhotic rats.

Animals↗
PubMed1987

Plasma catecholamines after insulin hypoglycemia in Sheehan's syndrome.

The plasma catecholamine response to hypoglycemia was studied in a group of hypopituitary patients with Sheehan's syndrome before (group A) and after (group B) combined cortisol and thyroid hormone treatment as well as in a group of normal women (group C). The mean basal plasma norepinephrine (NE) level was significantly increased in group A compared to levels in groups B and C, in which values were similar. The mean basal plasma epinephrine (E) level was not significantly altered by hypopituitarism. The plasma NE response to hypoglycemia was similar in the three groups, while the plasma E response was blunted in groups A and B. However, the plasma E response was significantly decreased only in half of the patients. The basal E/NE ratio was similar in the three groups, but it was significantly decreased in groups A and B compared to that in group C at the peak. From these data we conclude that 1) hypopituitarism is characterized in the basal state by increased adrenergic tone, probably related to secondary hypothyroidism; and 2) during hypoglycemia adrenal stimulation is impaired only in some patients. The role of ACTH in the regulation of E secretion is minor. Impaired neurogenic regulation in some patients with Sheehan's syndrome could contribute to their illness.

Adult↗
PubMed1987

Dilution of plasma with Tris buffer increases measured catecholamines in plasma.

We investigated the effects of dilution of plasma samples on the measured concentrations of catecholamines. Diluting samples of human plasma 10-, 50-, and 100-fold with Tris buffer (100 mol/L, pH 8.6) improved analytical recovery of internal standards, suggesting that it decreases the commonly observed inhibition of methylation in radioenzymatic assays of catecholamines in plasma. However, the dilution is not associated with a proportional decrease in counted radioactivity. This extra amount of radioactivity, which is unlikely to be nonspecific in origin, accounts for a significant increase in the calculated catecholamine concentration. Tentatively, we suggest that Tris buffer releases both catecholamines and conjugated catecholamines bound to some unidentified low-molecular-mass component of plasma.

Dopamine↗
PubMed1986

Plasma free, sulfo- and glucuro-conjugated catecholamines in uremic patients.

The metabolism of catecholamines (CA) in non-selected patients with chronic renal failure and under hemodialysis (CRFh) was studied by measuring the concentration of plasma free, sulfo- and glucuroconjugated CA, dopamine (DA), norepinephrine (NE), and epinephrine (EPI). Our data demonstrate a statistically significant increase of free DA and free NE concentration in CRFh, while that of free EPI was not different from controls. However a careful scrutiny of 35 individual data suggests that sub-groups of patients with either high normal or low plasma-free NE concentration could exist; this likely heterogeneity could be a good explanation for conflicting conclusions provided by previous reports. Suspecting that conjugated CA might be altered in CRFh, plasma sulfo- and glucuro-conjugated DA, NE and EPI were also measured. We have found a predictable and highly significant increase of sulfo-conjugated CA; plasma concentration of glucuro-conjugated DA and NE in CRFh was not different from controls, while that of glucuro-conjugated EPI was significantly increased. The physiological meaning, if any, of these new observations on conjugated CA cannot be assessed at the moment. The effects of hemodialysis were also investigated. Measurements on the arterial and on the venous line showed highly significant differences for tyrosine, free and sulfo-conjugated CA, and a lack of difference for glucuro-conjugated CA. Thus tyrosine, free and sulfo-conjugated CA were eliminated by the artificial kidney, but not glucuro-conjugated amines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effects of an intravenous infusion of noradrenaline on the plasma concentration of free and sulfoconjugated catecholamines in anesthetized dogs.

Exogenous noradrenaline (NA) was infused intravenously at increasing rate from zero (control) to 10, 25, 50, 100, 200 and 600 ng/kg/min during 20 min in anesthetized and ventilated dogs; the mean (+/- SEM) plasma concentration of free NA was increased from 130 +/- 23 pg/ml (basal) to 7,826 +/- 787 pg/ml. This had no measurable effect on the plasma concentration of dopamine and adrenaline in either free or sulfoconjugated form; a lack of change was also observed in dogs given a 600-ng/kg/min infusion during more than 2 h. The increase of free NA concentration was highly correlated both with the infusion rate, and with the blood pressure. Contrary to expectations, the plasma concentration of NA sulfate decreased in all 5 dogs when plasma NA concentration was progressively increased from basal to about 1,600 pg/ml; beyond this apparently crucial level (i.e. from about 1,600 to 7,826 pg/ml), the response of NA sulfate concentration was erratic, as it was in dogs given a 600-ng/kg/min infusion during more than 2 h. If the response of canine blood pressure is examined in the light of the level of free NA concentration, two mechanisms can be suspected: (1) when the NA level increased from basal to about 1,600 pg/ml, a direct action upon peripheral resistances was likely to be the predominant hypertensive mechanism; (2) beyond about 1,600 pg/ml, a combined effect of NA on both peripheral resistances and cardiac hemodynamics could have a role in the hypertensive process. Thus, a concentration of NA of about 1,600 pg/ml appears to be a landmark for both CA metabolism and circulatory homeostasis. Further studies will have to be carried out to investigate whether this represents the upper physiological concentration in the anesthetized dog.

Anesthesia↗