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  • 1
    Electronic Resource
    Electronic Resource
    Survival, haemodynamics and cardiac remodelling follow up in mice after myocardial infarction (2003)
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 30 (2003), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In the present study, the time-course, over a 1 year period, of postischaemic dilated cardiomyopathy and/or development of congestive heart failure was investigated in mice in terms of survival and cardiac functional and structural characteristics.2. C57BL/6 mice with myocardial infarction (MI mice; coronary ligation n = 78) or sham-operated animals (n = 45) were used and echocardiographic, haemodynamic and histomorphometric parameters were assessed at 3, 6 and 12 months post-MI.3. At 12 months, the survival rate was 70% in MI mice. Left ventricular dysfunction was evidenced by a strong decrease in ejection fraction (EF; −48 and −53% at 6 and 12 months, respectively; both P 〈 0.05) and an increase in left ventricular end-diastolic pressure (+100% at both 6 and 12 months; both P 〈 0.05). There was no major worsening in cardiac function between 6 and 12 months, suggesting strong compensatory mechanisms. Cardiac remodelling was observed, characterized by strong left ventricular hypertrophy (+38 and +62% at 6 and 12 months, respectively; both P 〈 0.05) and dilatation (+53% at 6 months; P 〈 0.05), but collagen was not significantly increased. Significant correlations were found between EF (echocardiography) and dP/dtmax, between end-diastolic volume (echocardiography) and left ventricular internal perimeter (histomorphometry) and between left ventricular mass (echocardiography) and weight.4. In conclusion, despite a high survival rate, the MI mouse model displays most of the hallmarks of postischaemic dilated cardiomyopathy and/or congestive heart failure, thus affording the necessary background for the subsequent evaluation of gene manipulation and/or drug effects. In addition, two-dimensional echocardiography appears to be a suitable tool for the long-term follow up of cardiac function and remodelling in this model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1681.2003.03784.x
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  • 2
    Electronic Resource
    Electronic Resource
    Coronary Dilatation Reserve In Experimental Hypertension And Chronic Heart Failure: Effects Of Blockade Of The Renin–Angiotensin System (2001)
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 28 (2001), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The aim of the present study was to investigate left and right ventricular (LV and RV, respectively) coronary vasodilatation reserve (CVR; fluorescent microsphere technique) in rats with hypertension (spontaneously hypertensive rats (SHR)) or congestive heart failure (CHF) and the effects of early and chronic renin–angiotensin system (RAS) blockade thereupon.2. In adult SHR, both LV and RV CVR were impaired, especially in the non-hypertrophied RV, the main factor involved being coronary vascular remodelling. Blockade of the RAS normalized both LV and RV CVR, mainly through the prevention of hypertension and suppression of the resulting pericoronary fibrosis.3. In postischaemic CHF rats, there was an early and severe degradation of LV and RV CVR that developed before any significant vascular remodelling and appeared to be linked to the deterioration of cardiac hypertrophy and haemodynamics. This degradation in CVR further worsened over the longer term due to late-developing pericoronary fibrosis and endothelial dysfunction. Blockade of the RAS had no early effects on LV and RV CVR, but improved RV CVR over the long term, mainly by limiting RV hypertrophy and by preventing the development of pericoronary fibrosis and coronary endothelial dysfunction.4. In kallikrein–kinin system-deficient mice, CVR was not different from that of wild-type mice, suggesting that this system is not implicated in normal CVR regulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1681.2001.03573.x
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  • 3
    Electronic Resource
    Electronic Resource
    β-Adrenoceptor blocking drugs, heart rate and genetic hypertension development in rats (1979)
    Springer
    Cellular and molecular life sciences 35 (1979), S. 656-657 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In spontaneously hypertensive rats (SHRs) chronically treated during their growth with β-adrenoceptor blocking drugs, no correlation was found between the reduction in heart rate and the prevention of genetic hypertension development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01960381
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  • 4
    Electronic Resource
    Electronic Resource
    Comparative β-adrenoceptor blocking effect and pharmacokinetics of bucindolol and propranolol in man (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 649-656 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00547043
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  • 5
    Electronic Resource
    Electronic Resource
    β-Adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 405-411 
    Details
    ISSN: 1432-1041
    Keywords: bornaprolol ; propranolol ; beta-adrenoceptor blockade ; duration of action ; pharmacokinetics ; plasma renin activity ; bronchoconstriction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β-adrenoceptor blocking effects and pharmacokinetics of bornaprolol (FM 24), a new β-adrenoceptor blocking agent, have been compared with those of propranolol and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate, systolic and diastolic blood pressures and peak expiratory flow rate were measured at rest and at the end of 3 min vigorous exercise on a bicycle ergometer, before and 2, 24 and 48 h after single oral doses of bornaprolol (120, 240 and 480 mg) and propranolol (40, 80 and 160 mg). Plasma renin activity at rest and the plasma concentrations of the two drugs were determined. Bornaprolol significantly reduced resting heart rate, dose-dependently lowered exercise-induced tachycardia and decreased peak expiratory flow rate and plasma renin activity. In addition, exercise-induced tachycardia was significantly reduced by bornaprolol up to 48 hours after drug intake (pharmacodynamic half-life approximately 63–86 h) and there was a correlation between this reduction and the log plasma bornaprolol concentration over the 48-h period. Thus, bornaprolol behaved in man as a non-cardioselective and long-lasting β-adrenoceptor blocking drug, probably devoid of intrinsic sympathomimetic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613453
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  • 6
    Electronic Resource
    Electronic Resource
    Ketanserin and the arterial baroreceptor reflex in normotensive subjects (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 27-33 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00609954
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  • 7
    Electronic Resource
    Electronic Resource
    Prospective study of the potentiation of acenocoumarol by amiodarone (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 625-629 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00607905
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  • 8
    Electronic Resource
    Electronic Resource
    Influence of sex on the clinical pharmacology of flutiorex, a new anorectic drug (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 325-330 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00565621
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  • 9
    Electronic Resource
    Electronic Resource
    Attenuation by diltiazem of arterial baroreflex sensitivity in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 675-679 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00541924
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  • 10
    Electronic Resource
    Electronic Resource
    Comparison of the effects of dilevalol and propranolol on systemic and regional haemodynamics in healthy volunteers at rest and during exercise (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 39-47 
    Details
    ISSN: 1432-1041
    Keywords: Dilevalol ; Propranolol ; intrinsic sympathomimetic activity ; healthy volunteers ; pulsed Doppler ; regional haemodynamics ; plasma renin activity ; plasma atrial natriuretic factor ; plasma norepinephrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of single oral doses of dilevalol 400 mg and propranolol 80 mg on systemic and regional haemodynamics at rest and after sub-maximal exercise, were compared, in a placebo-controlled, randomised, double-blind, crossover study in 6 healthy male volunteers. At rest, as compared to placebo, neither dilevalol nor propranolol significantly affected arterial pressure and heart rate but, whereas propranolol decreased cardiac output (−27% at 2 h) and tended to increase total peripheral resistance, dilevalol tended to increase cardiac output and decreased total peripheral resistance (−7% at 2 h). Neither dilevalol nor propranolol affected brachial artery diameter. Propranolol tended to decrease brachial artery flow (−20% at 2 h) and to increase brachial vascular resistance (+25% at 2 h), but dilevalol did not and the brachial irrigation ratios did not change. Neither of the drugs affected carotid haemodynamics or plasma atrial natriuretic factor. Both drugs tended to decrease plasma renin activity, and dilevalol (+82% at 2 h) increased norepinephrine more than propranolol (+19% at 2 h). After exercise, dilevalol and propranolol produced similar falls in the induced increases in arterial pressure, heart rate and cardiac output, and had the same effects on regional haemodynamics, plasma renin activity and atrial natriuretic factor. Finally, dilevalol greatly increased plasma norepinephrine. We conclude that the β2-adrenoceptor agonist activity of dilevalol was clearly expressed at rest, thus inducing vasodilation and counteracting the β-adrenoceptor blockade-induced negative chronotropic and inotropic effects. However, during sub-maximal exercise, only the β-adrenoceptor antagonist activity of dilevalol was apparent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193476
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