Atrioventricular block induced in an athlete by carotid baroreceptor stimulation.
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Adult↗
Biomedical subjects
R Fiocchi
Publications and source records attributed to R Fiocchi.
Platelet hypersensitivity to serotonin after prolonged ketanserin intake?
In the present study the effect of acute and short-term ketanserin administration on serotonin (5-HT)-induced aggregation was investigated in eight healthy volunteers. They received 40 mg ketanserin three times a day for 1 week. Blood samples were drawn before (A), 1.5 h after the first dose (B), 12 h after the evening dose of the 7th day (C), and 1.5 h after the morning dose of the 8th day (D). The maximal rate of aggregation (mm/min +/- SEM) was significantly decreased following the first dose (A: 47.6 +/- 6.0; B: 27.6 +/- 4.5; p less than 0.05); 12 h after the evening dose of the 7th day, the platelets aggregated more rapidly with 5-HT than before the onset of the study (C: 69.4 +/- 6.0; A vs. p less than 0.01). The last dose of ketanserin abolished this hyperresponsiveness (D: 46.1 +/- 7.58; C vs. D, p less than 0.05); however, there was no significant difference in the velocity of aggregation between the onset of the study and after the last dose. It appears that ketanserin has a double effect on platelet aggregation: an initial hyporesponsiveness to 5-HT is followed by a delayed hyperresponsiveness that is temporarily corrected by renewed ketanserin intake. In vitro dose-response curves suggested that prolonged ketanserin intake results in a higher "sensitivity" of the platelets to serotonin rather than a refractoriness of the platelets to ketanserin.
Adult↗
Effects of ketanserin on the intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes of normal male subjects.
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.
Cell Membrane Permeability↗
Hemodynamic response to chronic ketanserin treatment in essential hypertension.
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.
Adult↗
Double-blind comparison of ketanserin with propranolol in hypertensive patients: interim report.
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).
Adult↗
The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise.
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.
Adult↗
Ketanserin: a new hypotensive drug?
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.
Animals↗
Relationship between carotid baroreflex sensitivity, physical fitness and activity in cyclists.
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.
Adolescent↗
Differential responses of plasma aldosterone, cortisol and adrenocorticotropin to two dopamine receptor antagonists.
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.
Adrenocorticotropic Hormone↗
The peripheral narcotic antagonist N-allyl levallorphan-bromide (CM 32191) selectively prevents morphine antipropulsive action and buprenorphine in-vivo binding in the rat intestine.
The assumed low ability of the quaternary narcotic antagonist N-allyl levallorphan-bromide (CM 32191) to cross the blood-brain barrier and its selectivity in relieving the peripherally-elicited antipropulsive action of morphine while preserving analgesia has been tested. To ascertain the extent of penetration of CM 32191 into the cns, its relative potency in preventing the in-vivo binding of high specific activity [3H]buprenorphine in the rat cns and small intestine was compared. Pretreatment was with CM 32191 at 16, 30 or 60 mg kg-1 s.c., 20, 60 or 120 min before buprenorphine, the concentrations of which in cerebrum and spinal cord were comparable with control values, but were consistently reduced in the intestine (longitudinal muscle with attached myenteric plexus). Pretreatment with naloxone (20 min, 0.5 or 1 mg kg-1 s.c.) lowered buprenorphine binding in intestine and cns. Neither narcotic antagonist produced significant changes in buprenorphine plasma concentrations. The peripheral selectivity of CM 32191, methyl naloxone and naloxone was examined by investigating in the same rats nociception in the hot plate (central opiate-sensitive mechanism) and the transit of a charcoal meal along the small intestine (local opiate-sensitive mechanism). Both effects were inhibited by morphine (5 mg kg-1 i.v.). Naloxone (10 min pretreatment, 0.5 or 1 mg kg-1 s.c.) did not selectively antagonize intestinal action of the morphine since the relief of charcoal transit inhibition was consistently associated with complete loss of analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Central and peripheral inhibition of gastrointestinal transit in rats: narcotics differ substantially by acting at either or both levels.
The roles of local intestinal and centrally mediated opiate-specific mechanisms underlying gastrointestinal transit inhibiton by five typical narcotic analgesics were assessed by the rat charcoal meal test. The doses (mg kg-1 s.c.) reducing the progression of charcoal to 50% of drug-free controls in 5 min (ID50) were approximately 1 for morphine and methadone, 0.5 and 40 for diamorphine and pethidine (all given 25 min before charcoal) and 0.001 for etorphine (10 min before charcoal). The delay in test meal travel caused by these ID50 doses was completely prevented by i.p. naloxone. Intracerebroventricular (i.c.v.) naloxone fully antagonized pethidine and etorphine but had no effect on morphine. Morphine, but either pethidine nor etorphine, was antagonized by i.p. N-methyl naloxone (a peripheral antagonist). Diamorphine and methadone were partially antagonized by i.c.v. naloxone or i.p. N-methyl naloxone.
Analgesics, Opioid↗
Haemodynamic and humoral responses to chronic ketanserin treatment in essential hypertension.
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 six weeks. Resting intra-arterial 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 haemodynamic 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. Mean pulmonary arterial pressure and capillary wedge pressure were not significantly affected, but pulmonary vascular resistance decreased by 15%. The pressor response to methoxamine was significantly reduced by ketanserin. Both plasma noradrenaline and adrenaline concentrations increased, plasma renin activity and angiotensin II concentration decreased, and plasma aldosterone concentration was unchanged. The data indicate that ketanserin induces arteriolar dilatation, possibly related to an alpha-1-antagonistic action and to a reduced circulating angiotensin II concentration. The haemodynamic response is complex, and an increase in cardiac output limits the hypotensive effect. There is no firm evidence of an effect on venous tone as cardiac filling pressures do not change.
Adult↗
Prenalterol in the treatment of orthostatic hypotension in Shy-Drager syndrome.
The effects of prenalterol, a selective beta 1-adrenoreceptor agonist, were studied in a patient with the Shy-Drager syndrome, presenting with incapacitating orthostatic hypotension. The main haemodynamic defect was an impressive postural fall in stroke volume and cardiac output pointing to denervation of the capacitance vessels. Prenalterol 4 X 30 mg orally produced a marked increase in supine and standing blood pressure, along with substantial symptomatic improvement. Notable positive chronotropic and inotropic effects were observed. Association of fludrocortisone 0.5 mg/day resulted in further haemodynamic and symptomatic improvement, presumably due to plasma volume expansion. Haemodynamically, prenalterol and fludrocortisone resulted in a substantial increase in standing cardiac output, primarily due to the chronotropic effects of prenalterol. In addition to the haemodynamic effects, prenalterol stimulated the renin-aldosterone system and restored the normal diurnal pattern of water and sodium excretion, the latter may have contributed to the improvement of orthostatic tolerance. Prenalterol could be a valuable adjunct to the existing treatment schedules of neurogenic orthostatic hypotension.
Adrenergic beta-Agonists↗
Alpha 1 antagonistic and antiserotoninergic action during administration of ketanserin.
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Adrenergic alpha-Antagonists↗
Quaternary narcotic antagonists' relative ability to prevent antinociception and gastrointestinal transit inhibition in morphine-treated rats as an index of peripheral selectivity.
Single doses of naloxone (0.025 to 0.5 mg/kg) or of one of four quaternary narcotic antagonists (i.e. nalorphine allobromide, nalorphine methobromide, naloxone methobromide or naltrexone methobromide, 1 to 60 mg/kg) were given s.c. to rats before morphine, 5 mg/kg i.v. In the absence of antagonists morphine reduced G.I. transit of a charcoal meal to about 15% of drug-free controls and consistently delayed nociceptive reactions (55 degrees C hot plate) in all animals. Doses of antagonists slightly reducing morphine antinociception (centrally effective = A) and restoring G.I. transit to about 50% of drug-free rats (peripherally effective = B) were estimated. The A:B ratio, indicating peripheral selectivity, was at least 8 for any of the quaternary antagonists given 10 min before morphine, but prolonging this interval may have resulted in a lower figure (i.e. less peripheral selectivity) because of reduced A and increased B. This was definitely so for naltrexone methobromide (A:B, greater than 60 at 10 min, about 1 at 80 min) and was not apparent for nalorphrine methobromide according to available data, which for nalorphrine allobromide and to a lesser extent for naloxone methobromide showed only an increase in B at intervals longer than 10 min. Both morphine-induced antinociception and inhibition of G.I. transit were reduced by naloxone at the lower doses tested and were fully prevented at the higher. These findings indicated that, unlike naloxone, the investigated quaternary narcotic antagonists are interesting prototype drugs for selective blockade of opiate receptors outside the CNS, although certain critical aspects, possibly biological N-dealkylation to the corresponding tertiary antagonists, condition peripheral selectivity.
Analgesia↗
Neurovascular island flaps in the emergency reconstruction of the terminal phalanx of the thumb.
The technique of neurovascular island flaps is described applied as an emergency operation in six patients who presented with considerable loss of substance of the fleshy pulp of the thumb or total loss of the terminal phalanx. The writers consider that the reconstructive method described by them is an advance on the traditional method, since not only can the matter be resolved in a single operative session, but epicritic sensitivity is maintained, the length of the thumb remains unaltered, better aesthetic results are obtained, and there are no vasomotor or sympathetic disorders.
Adult↗
Complications and technical errors in endo- and arthroprostheses of the wrist and hand. A critical reappraisal of 89 operations.
The authors analyse eighty-nine operations performed between 1969 and 1975 for the insertion of endo- and arthroprostheses is the wrist and hand, with special reference to the complications and errors of technique of this type of surgery. They have paid particular attention to possible errors of diagnosis, faulty indications, and technical operative errors. They confirm that this type of surgery, which is still in the developmental stages, should be restricted to carefully selected cases and performed only in specialist centres.
Adolescent↗