scispace - formally typeset
Search or ask a question

Showing papers by "Robert Fagard published in 1985"


Journal ArticleDOI
TL;DR: In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.

1,328 citations


Journal ArticleDOI
TL;DR: The tendency of the correlation coefficients for body weight and body mass index to be higher in mother-offspring than in father-offpring pairs suggests a closer maternal role in the determination of calorie intake in offspring.

47 citations



Journal ArticleDOI
TL;DR: To evaluate differences between athletes and controls, PRA, ANG II, and 6-keto-PGF1 alpha were first adjusted for significant confounding factors, such as age, weight, hematocrit, 24-h urinary sodium excretion, and O2 uptake.
Abstract: Twelve male runners and 12 matched nonathletes performed a prolonged uninterrupted graded exercise test on the bicycle ergometer up to exhaustion to study blood pressure and plasma levels of renin (PRA), vasoconstrictor angiotensin II (ANG II), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a metabolite of the vasodilator prostacyclin. In the athletes work load was increased by 30 W/4 min, and in the control subjects the increments of work load were adjusted to their lower exercise capacity to equalize total exercise duration. Blood was drawn, and blood pressure and O2 uptake (VO2) were measured at rest and at the fourth, eighth, and last steps of exercise. Peak VO2 averaged 60 +/- 1.6 ml . min-1 . kg-1 in the runners and 46.8 +/- 1.5 in the nonathletes. To evaluate differences between athletes and controls, PRA, ANG II, and 6-keto-PGF1 alpha were first adjusted for significant confounding factors, such as age, weight, hematocrit, 24-h urinary sodium excretion, and O2 uptake. PRA was significantly lower in the athletes (F = 11.2; P less than 0.01); ANG II was not different at rest, but its rise with exercise was less steep in the runners (F = 8.2; P less than 0.01), whereas 6-keto-PGF1 alpha was not different between the groups (F = 1.3; NS). Despite the differences in PRA and ANG II, however, blood pressure was similar in athletes and nonathletes (F = 0.0; NS).

34 citations



Journal ArticleDOI
TL;DR: During exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, and the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise is not supported.
Abstract: After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.

27 citations


Journal ArticleDOI
TL;DR: The change in BP after 3 months on K treatment was positively and independently related to both the initial BP and the concurrent changes in body weight, and that up to the 2nd month after randomization, systolic BP was significantly higher in the K than in the P group, whereas the differences in diastolic BP were mostly not significant.
Abstract: This double-blind study, which is still in progress, aims to compare ketanserin (K) and propranolol (P) during long-term treatment of hypertensive patients in general practice. After a run-in period on placebo, active treatment was initiated with 20 mg K or 40 mg P, b.i.d., during a 2-week period, whereafter the daily dose of either drug was doubled. Presently, 331 patients have been randomized, two-thirds to the K group (n = 221) and one-third to the P group (n = 110). Both groups were similar at randomization, with blood pressure (BP) averaging 171/105 mm Hg. The presently available data concerning the initial 3 months of the trial show that up to the 2nd month after randomization, systolic BP was significantly (p less than 0.05) higher in the K than in the P group, whereas the differences in diastolic BP were mostly not significant. The change in BP after 3 months on K treatment was positively and independently related to both the initial BP and the concurrent changes in body weight. Heart rate was lower (p less than 0.001) during P, whereas body weight was not statistically different between both groups. Differences in complaints between the K and P group were small. However, in the K group dry mouth was transiently more frequently reported at 1 month (p = 0.02) and multiple complaints at 3 months (p = 0.03).

19 citations


Journal ArticleDOI
TL;DR: The possible use of ketanserin for the chronic treatment of patients with essential hypertension was discussed based on the data exposed at this symposium, and the drug could be particularly indicated in elderly hypertensive patients, especially in those with peripheral vascular disease.
Abstract: The possible use of ketanserin for the chronic treatment of patients with essential hypertension was discussed based on the data exposed at this symposium. Its hypotensive effect is established during placebo controlled trials, but more data are needed to determine its relative potency compared to standard hypotensive drugs. The drug seems to act by reducing systemic vascular resistance, but the relative role of the serotonin and alpha inhibition in the chronic hypotensive effect in man is not yet known. Subjective side effects occur after the first dose, but seem to be less frequent during chronic treatment; organ toxicity has not been reported in the therapeutic doses. The drug could be particularly indicated in elderly hypertensive patients, especially in those with peripheral vascular disease. The influence on morbidity and mortality is not yet known.

14 citations


Journal ArticleDOI
TL;DR: The results suggest that in man the so defined sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating barore Flex sensitivity.
Abstract: Carotid baroreceptors were stimulated with neck suction in 47 healthy subjects. Pulse interval lengthening was measured and the time course of the response was evaluated. Eight intensities of neck chamber suction were applied to select a criterion for computing the “RR response” that gives a significant linear relationship with the magnitude of the stimuli in the highest number of individuals. The best criterion was the maximal RR prolongation within 5 seconds after the onset of the stimulus. The slope of this relationship was defined as baroreflex sensitivity. The effect of physical fitness on baroreceptor function was investigated in 24 cycling tourists with a wide range of peak oxygen uptake and training characteristics. Baroreflex sensitivity averaged 7.3±0.8 msec · mm Hg−1 and was not significantly related to age, weight, basal heart rate, peak oxygen uptake and ventilation and other training characteristics. The results suggest that in man the so defined sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating baroreflex sensitivity.

13 citations



Journal ArticleDOI
TL;DR: The increment in the plasma renin activity, plasma angiotensin II, and plasma and urinary aldosterone excretion indicate a stimulation of the renin-aldosterone axis in this menstrual period.

Journal ArticleDOI
TL;DR: Log PRA at rest is inversely related to the subject's physical fitness, and a combination of two or more independent variables yielded significant partial correlation coefficients with log PRA.
Abstract: The relationship between plasma renin activity (PRA) at rest and physical fitness was studied in 40 normal young subjects on a liberal sodium intake.

Journal ArticleDOI
TL;DR: The results indicate that short-term ketanserin administration decreases the intraerythrocyte sodium concentration, but the flux measurements can not explain this observation.
Abstract: The effect of acute and short-term administration of ketanserin on the intracellular concentrations and transmembrane fluxes of sodium and potassium was studied in erythrocytes of 12 sodium-replete normal male subjects. The subjects received 40 mg ketanserin three times a day for 1 week. Blood samples were drawn before and 1.5 h after the first dose, 12 h after the evening dose of the 6th day, and 1.5 h after the morning dose of the 7th day. The intraerythrocyte sodium concentration was not changed after the first dose of ketanserin, but was decreased during short-term treatment with ketanserin. The ouabain-sensitive 86Rb-uptake, an estimate of the Na+,K+-adenosine triphosphatase pump activity, was decreased after acute ketanserin administration, but not during short-term treatment. This change in intraerythrocyte sodium concentration was related to the change in ouabain-sensitive 86Rb-uptake. The red cell Na+,K+-cotransport and Na+,Li+-countertransport transport activity were not changed during acute and short-term administration of ketanserin. These results indicate that short-term ketanserin administration decreases the intraerythrocyte sodium concentration, but the flux measurements can not explain this observation.

Journal ArticleDOI
TL;DR: It is suggested that the vasodilating mechanisms in the working muscles and the vasoconstricting mechanism in the non-working vascular beds are powerful and dominant during isotonic exercise and attenuate the opposing or additive vasoconStrictor effects of angiotensin II.
Abstract: To evaluate the effect of isotonic exercise on the response to angiotensin II, angiotensin II in saline solution was infused intravenously (7.5 ng · kg−1 · min−1) in seven normal sodium replete male volunteers before, during and after a graded uninterrupted exercise test on the bicycle ergometer until exhaustion. The subjects performed a similar exercise test on another day under randomized conditions when saline solution only was infused.

Journal ArticleDOI
TL;DR: Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased, and the pressor responses to methoxamine and to phenylephrine were reduced by ketanserin.
Abstract: Ketanserin (120 mg/day) or placebo was given orally to 14 patients with mild to moderate essential hypertension according to a double-blind crossover protocol, each treatment period lasting 6 weeks Resting intraarterial pressure in the recumbent position was reduced from 150/84 to 141/77 mm Hg; the hypotensive effect persisted throughout an uninterrupted graded exercise test to the point of exhaustion The hemodynamic effects were similar at rest and during exercise Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased The pressor responses to methoxamine and to phenylephrine were reduced by ketanserin

Journal Article
TL;DR: The differential responses of plasma aldosterone and cortisol to high doses of metoclopramide and domperidone are therefore, at least partially, mediated via the enhanced adrenal stimulation by ACTH after metoclocorticotropin.
Abstract: The response of plasma aldosterone, cortisol and adrenocorticotropin (ACTH) to the dopamine antagonists metoclopramide and domperidone, administered intravenously in a dose of 1 mg/kg, was investigated in healthy volunteers. Within 15 min after metoclopramide administration, plasma aldosterone (+ 99%), cortisol (+ 75%) and ACTH (+ 55%) increased (p less than 0.001), whereas the plasma levels of these hormones were not altered after domperidone. The differential responses of plasma aldosterone and cortisol to high doses of metoclopramide and domperidone are therefore, at least partially, mediated via the enhanced adrenal stimulation by ACTH after metoclopramide.

Journal ArticleDOI
TL;DR: The intracellular concentration and transmembrane fluxes of sodium and potassium were studied in the red blood cells of normal men and women in the two halves of their menstrual cycle to take into account sex-related variability.
Abstract: The intracellular concentration and transmembrane fluxes of sodium and potassium were studied in the red blood cells of normal men and women in the two halves of their menstrual cycle. Compared to men, the intra-erythrocyte sodium concentration was lower in women during the second half of the menstrual cycle. These two groups were similar for Na+, K+-ATPase pump activity estimated from the ouabain-sensitive 86rubidium-uptake and for the furosemide-sensitive sodium and potassium efflux. Women in the first half of the menstrual cycle, had intra-erythrocyte sodium concentration similar to men, but their furosemide-sensitive sodium efflux was lower. A lower intra-erythrocyte sodium concentration was observed in the second half as compared to the first half of the menstrual cycle in women. No significant difference was observed in the intra-erythrocyte potassium concentration and transmembrane fluxes of potassium in men and women in either half of the menstrual cycle. Therefore one should take into account sex-related variability when studying cationic fluxes and concentrations in red blood cells of men and women.


Journal ArticleDOI
TL;DR: The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid‐activable inactive renin was studied in nine healthy, sodium‐replete men, both at rest and exercise.
Abstract: The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (P = 0.004), total (P less than 0.001) and inactive (P = 0.02) renin at rest recumbent and at rest, sitting. Inhibition of prostaglandins with indomethacin reduced (P less than 0.001) active and total renin at each level of work load but not (P = 0.32) inactive renin. However the exercise-induced stimulation (P less than 0.05) of active and of total renin still occur during indomethacin. Indomethacin reduced (P less than 0.001) at rest, sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2, prostaglandin F2 alpha and 13, 14-dihydro-15-keto-prostaglandin F alpha; the urinary excretion of immunoreactive prostaglandin E2 and F2 alpha were also reduced.

Journal Article
TL;DR: The results suggest that in man the so-called sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating barore Flex sensitivity.
Abstract: Carotid baroreceptors were stimulated with neck suction in 24 cycling tourists and pulse interval lengthening was measured. Eight intensities of neck chamber suction were applied to select a criterion for computing the RR response that gives a significant linear relationship with the magnitude of the stimuli in the highest number of individuals. The best criterion was the maximal RR prolongation within 5 s after the onset of the stimulus. The slope of this relationship was defined as baroreflex sensitivity. Baroreflex sensitivity averaged 7.3 +/- 0.8 ms/mmHg. The cycling tourists underwent an exercise test on a bicycle ergometer until exhaustion, and oxygen uptake, pulmonary ventilation, peak heart rate and exercise duration were determined. In single and multiple regression analysis, baroreflex sensitivity was not significantly related to basal heart rate, peak oxygen uptake and ventilation, duration of exercise or other training characteristics. The results suggest that in man the so-called sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating baroreflex sensitivity.

Journal Article
TL;DR: The results indicate that short-term ketanserin administration decreases the intra-erythrocyte sodium concentration, but the flux measurements cannot explain this observation.
Abstract: The effect of acute and short-term administration of ketanserin on the intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes was studied in 12 sodium-replete, normal male subjects. The subjects received 40 mg ketanserin three times a day for one week. Blood samples were drawn before and 2.5 hours after the first dose, 12 hours after the evening dose of the sixth day and 1.5 hours after the morning dose of the seventh day. The intra-erythrocyte sodium concentration was not changed following the first dose of ketanserin, but was decreased (p less than 0.05) during short-term treatment with ketanserin. The ouabain-sensitive 86Rb-uptake, an estimate of the Na+,K+-ATPase pump activity, was decreased (p less than 0.001) after acute ketanserin administration, but not (p = 0.07) during short-term treatment. This change in intra-erythrocyte sodium concentration was related (r = 0.73, p less than 0.01) to the change in ouabain-sensitive 86Rb-uptake. The red cell Na+,K+-cotransport and Na+,Li+-countertransport activity were not changed during acute and short-term administration of ketanserin. The results indicate that short-term ketanserin administration decreases the intra-erythrocyte sodium concentration, but the flux measurements cannot explain this observation.

Book ChapterDOI
01 Jan 1985
TL;DR: Unter Verwendung verschiedener nicht invasiver Untersuchungsverfahren wurde bei Patienten mit koronarer Herzerkrankung die Struktur and Funktion des Herzens vor and nach einem korperlichen Training untersucht.
Abstract: Unter Verwendung verschiedener nicht invasiver Untersuchungsverfahren (Elektrokardiogramm, CO2-Ruckatmung, Apexkardiogramm, Carotispulskurve) wurde bei Patienten mit koronarer Herzerkrankung die Struktur und Funktion des Herzens vor und nach einem korperlichen Training untersucht.