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  • 1
    ISSN: 1432-1238
    Keywords: Hypovolemia ; Cardiac output ; Regional blood flows ; Cardiovascular reflexes ; Catechol-amines ; Healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To describe the evolution of systemic and regional blood flows during and after hypovolemia in humans. Design Simulation of hypovolemia by a prolonged application of lower body negative pressure (LBNP). Setting Laboratory of Clinical Research, Surgical Intensive Care Unit of an University Hospital. Participants 8 healthy male volunteers. Interventions 3 successive and increasing 15min-levels of LBNP were followed by a progressive return (10 min) to atmospheric pressure, then a 60min-recovery period. Measurements and main results Simulated hypovolemia induced a parallel one-third decrease in cardiac output (bioimpedance), musculocutaneous (venous plethysmography) and splanchnic (ICG clearance) blood flows. Adrenergic-mediated peripheral vasoconstriction prevented any change in mean arterial pressure. The decrease in renal blood flow (PAH clearance) was limited, glomerular filtration rate (inulin clearance) unchanged and thus filtration fraction increased. All the cardiovascular and biological variables returned to pre-LBNP values during the recovery period except for splanchnic blood flow which remained below control values 60 min after the return to atmospheric pressure. Conclusions Since a sustained splanchnic vasoconstriction follows a transient normotensive hypovolemia in healthy men despite adequate treatment considering arterial pressure and cardiac output, the therapeutic goals of fluid resuscitation after hypovolemic shock might be revisited and a supranormal value of cardiac output proposed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1238
    Keywords: Cyanide ; Hydroxocobalamin ; Cobalt edetate ; Catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives The hemodynamic effects of two cyanide antidotes, hydroxocobalamin and cobalt edetate were compared. Design This experimental study was performed in chronically instrumented conscious dogs and at equipotent cyanide antidotal doses (hydroxocobalamin 70 mg·kg−1; cobalt edetate 10.5 mg·kg−1). Results Peak plasma cobalt concentrations did not differ in the two groups (412±183 vs 400±160 μmol·1−1). Hydroxocobalamin induced a slight increase in mean arterial pressure (+17±9%,p〈0.05) and systemic resistance (+19±15%,p〈0.05). In contrast, cobalt edetate induced an increase in heart rate (+78±33%,p〈0.05), in cardiac output (+63±39%,p〈0.05), and in maximum rise of left ventricular pressure (+33±15%,p〈0.05), did not modify mean arterial pressure, and decreased systemic resistance (−36±15%,p〈0.05). These hemodynamic effects were associated with an increase in plasma catecholamine concentrations (epinephrine: 2524±3025 vs. 58±37 pg·ml−1,p〈0.05; norepinephrine: 1106±609 vs. 343±146 pg·ml−1,p〈0.05), which in contrast remained unchanged after hydroxocobalamin administration. Cobalt edetate also induced an increase in blood glucose concentrations (9.9±1.9 vs. 6.1±1.2 mmol·l−1,p〈0.05) and a moderate metabolic acidosis, whereas hydroxocobalamin did not. After adrenergic (α1,β) and cholinergic receptor blockade, cobalt edetate did not modify heart rate and various indices of cardiac function, suggesting that it has no direct cardiac effects. Conclusion Considering its lack of hemodynamically relevant effects, these results indicate that hydroxocobalamin is potentially a safer cyanide antidote than cobalt edetate.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 10 (1976), S. 325-330 
    ISSN: 1432-1041
    Keywords: Flutiorex ; pharmacokinetics ; sex ; anorectic agent ; sympathetic stimulation ; CNS stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of flutiorex, a new anorectic agent, and of a placebo on food intake and the activity of the sympathetic and central nervous systems have been compared in a double blind trial in two groups of healthy volunteers, one of five males and the other of five females. Flutiorex 20 mg orally had a significant anorectic effect both in males and females, the observed reduction in food intake being 34.0 and 27.5%, respectively. It caused α-adrenergic stimulation (blood pressure and pupil diameter) and central nervous system excitation (critical flicker frequency), both of which were more marked in males than in females. Flutiorex was better tolerated by women than by men. Measurement of the blood level of flutiorex and its de-ethylated metabolite, norflutiorex, showed that both compounds were detectable in four of the five male subjects, but in only one of the five females. Sex-linked differences in the pharmacokinetics of flutiorex may explain the greater intensity of its effects in males.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 675-679 
    ISSN: 1432-1041
    Keywords: diltiazem ; baroreflex sensitivity ; plasma catecholamines ; normotensive subjects ; baroreceptor testing ; phenylephrine ; nitroglycerin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of oral diltiazem 120 mg, on the responses to baroreflex activation and deactivation by phenylephrine and nitroglycerin, respectively, were investigated in normotensive subjects, with simultaneous measurement of plasma catecholamine levels. Diltiazem significantly reduced the tachycardia induced by bolus injections of nitroglycerin and abolished the concomitant increase in plasma noradrenaline. It also significantly decreased the bradycardiac response to phenylephrine infusion. Diltiazem reduced, although not significantly so, the bradycardia induced by boluses of phenylephrine. The overall reduction in baroreflex sensitivity, which might contribute to the limited tachycardiac effect of diltiazem in man, is consistent with the drug-induced attenuation of the sympathetic and also of the parasympathetic components of the baroreceptor reflex.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 625-629 
    ISSN: 1432-1041
    Keywords: amiodarone ; acenocoumarol ; antivitamin K ; drug interaction ; prothrombin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of oral amiodarone on the anticoagulant effect of the coumarine derivative acenocoumarol has been investigated prospectively in 10 patients with normal renal, hepatic and haematological function and who were not in cardiac failure. The daily dose of acenocoumarol was sufficient to produce a prothrombin activity of 25 to 35%. When the prothrombin time had become stable amiodarone 600 mg/d was administered for 1 week followed by 400 mg/d for the next 3 weeks. A decrease in prothrombin activity from 30.5 to 20.2% was observed, associated with a decrease in vitamin K coagulation factors, after a mean of 4 days following commencement of amiodarone. In 6 patients a prothrombin activity 〈20% required a 60% reduction in the dose of acenocoumarol after 1 week of amiodarone 600 mg, and a 33% reduction after 3 weeks of amiodarone 400 mg. There was no correlation between the plasma amiodarone and the decrease in prothrombin activity. Inhibition of acenocoumarol metabolism by amiodarone is the most likely explanation of these findings.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 27-33 
    ISSN: 1432-1041
    Keywords: ketanserin ; baroreflex sensitivity ; plasma catecholamines ; plasma renin ; alpha1-adrenoceptor blockade ; normotensive subjects ; baroreceptor reflex ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oral ketanserin 40 and 120 mg on the responses to baroreflex activation and deactivation by phenylephrine and nitroglycerin, respectively, were investigated in normotensive subjects. Plasma catecholamine levels were measured at the same times. Two hours after the administration of ketanserin, and regardless of its effect on arterial pressure (no change after 40 mg, decrease after 120 mg), there was no alteration either in resting heart rate or baroreflex sensitivity during baroreceptor activation or deactivation. The lack of reflex tachycardia in response to the drug-induced hypotension may be related to the α1-adrenoceptor blockade-mediated sympathoinhibitory effect of ketanserin, which leaves unaffected both plasma catecholamines and the normal reactivity of the sympathetic system.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1985), S. 649-656 
    ISSN: 1432-1041
    Keywords: bucindolol ; propranolol ; beta-adrenoceptor blockade ; intrinsic sympathomimetic activity ; vasodilator ; pharmacokinetics ; blood pressure ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β-adrenoceptor blocking properties and pharmacokinetics of bucindolol 150 mg were compared to those of propranolol 80 mg and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and peak expiratory flow rate (PEFR) at rest and during vigorous exercise, and plasma renin activity (PRA) at rest, were measured before and at intervals up to 24 h after oral administration of the drugs. Bucindolol reduced exercise tachycardia and decreased exercise PEFR, thus behaving as a non-selective β-adrenoceptor blocking drug. In contrast to propranolol, bucindolol did not reduce resting HR and PRA, probably because of its intrinsic sympathomimetic activity. It decreased resting DBP in relation to its peripheral vasodilator properties. The effects of bucindolol developed as early as 30 min after administration and lasted up to 24 h, whereas its Tmax and T1/2 were 1.6 and 3.6 h respectively. Comparison of the time courses of plasma bucindolol and the cardiac β-adrenoceptor blockade strongly suggests that in man bucindolol undergoes an extensive first-pass effect, leading to the formation of one or more active metabolites.
    Type of Medium: Electronic Resource
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