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  • 1
    ISSN: 1432-1041
    Keywords: beta-blocking drugs ; coronary artery disease ; myocardial infarction ; haemodynamic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theoretically the increased sympathoadrenal activity following acute myocardial infarction might augment the haemodynamic impact of beta-adrenoceptor blockade. To evaluate this question 32 haemodynamic studies were performed to compare the effects of equivalent beta-blocking doses of propranolol (8 mg i.v.) and pindolol (0.8 mg i.v.) in patients with a recent acute myocardial infarction (A.M.I.) or stable coronary artery disease (and a presumptive low sympathetic state). In stable coronary artery disease there were clear differences between the haemodynamic impact of propranolol and pindolol. Propranolol decreased both heart rate (ΔHR −7 beat/min) and cardiac index (ΔCI −0.4l/min/m2), with an increased pulmonary artery occluded pressure (ΔPAOP +4 mmHg) and systemic vascular resistance index (ΔSVRI +358 dyn · s · cm−5 m2). However an equivalent beta-blocking dose of pindolol increased PAOP (ΔPAOP +3 mmHg) leaving other variables unchanged. These differential actions of propranolol and pindolol have previously been ascribed to the intrinsic synpathomimetic activity (I.S.A.) of pindolol maintaining cardiac pumping function in a low sympathetic state. In contrast following myocardial infarction, both drugs reduced cardiac index to a significantly greater extent compared with stable coronary artery disease (ΔCI propranolol −0.8l/min/m2; pindolol −0.4l/min/m2;p〈0.05); propranolol also reduced the systemic arterial blood pressure (Δsystolic −10 mmHg; Δmean −5 mmHg;p〈0.05). The haemodynamic relevance of the I.S.A. of pindolol appeared attenuated following A.M.I. These data are compatible with experimental evidence of sympathetic nervous activation following coronary occlusion; the resulting hyperadrenergic state appears to condition an augmented haemodynamic response to beta-blocking drugs irrespective of their ancillary pharmacological properties. The implications of these findings for clinical therapy warrant further examination.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 323-327 
    ISSN: 1432-1041
    Keywords: metoprolol ; coronary heart disease ; haemodynamics ; i.v. metoprolol ; dose-response effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of intravenous metoprolol, over the dose-range 2.5–20 mg, were studied in 12 patients with coronary heart disease. The pharmacodynamic activity of the drug was confirmed by the suppression of exercise systolic pressure and tachycardia. There were statistically significant dose-response reductions in systolic and diastolic pressures, heart rate and cardiac output together with a dose-related increase in pulmonary wedge pressure. In patients with coronary heart disease intravenous metoprolol should probably not exceed the doses used in this study and should be administered with caution in patients with impairment of pumping function.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: beta-receptor blocking drugs ; myocardial infarction ; haemodynamic effects ; propranolol ; pindolol ; intrinsic sympathomimetic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relevance of the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds to the clinical therapeutics of acute myocardial infarction was evaluated in 20 patients with an uncomplicated acute myocardial infarction by comparing the haemodynamic effects of equivalent beta-blocking doses of propranolol (non-cardioselective; no ISA) and pindolol (non-cardioselective; 50% ISA). Consecutive eligible male patients admitted to a Coronary Care Unit were randomised following a 1 h control period to two separate studies. In Study 1 the short-term dose-response effects of propranolol (1–8 mg) or pindolol (0.1–0.8 mg) were assessed. In Study 2 comparison of the effects of single i.v. propranolol (8 mg) and pindolol (0.8 mg) doses was undertaken over 6 h. Haemodynamic variables and thermodilution cardiac output were subsequently recorded to compare the effects of each drug on the circulation. The plasma concentrations of propranolol and pindolol were in the recognised therapeutic range. Both drugs were clinically well-tolerated, the changes induced in haemodynamic variables following each drug demonstrated effective beta-blockade. Within the limits of the experimental protocol, these data did not suggest definite haemodynamic advantage for ISA of pindolol in acute myocardial infarction. These findings are perhaps due to sympathetic activation in acute myocardial infarction attenuating the haemodynamic impact of ISA.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: coronary heart disease ; beta-blockade ; haemodynamics ; propranolol ; pindolol ; intrinsic sympathomimetic activity ; partial agonist activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To determine whether the depression of left ventricular pumping activity associated with beta-blockade alone could be offset by a substantial degree of partial agonist activity, the haemodynamic dose-response effects of intravenous propranolol and pindolol were compared in a randomised between-group saline controlled study in twenty patients with angiographically proven coronary artery disease. The intravenous doses of propranolol (2–16 mg) and pindolol (0.2–1.6 mg) used were selected on the basis of published reports of equivalence in terms of exercise blockade of chronotropic beta-adrenoceptors. Following four intravenous boluses of each drug, administered according to a cumulative log-dosage schedule, there was a log-linear increase in the plasma concentrations of each drug. The range of plasma concentrations achieved were those which have been shown to be associated with substantial attenuation of sympathetic stimulation of cardiac beta-adrenoceptors. At rest propranolol resulted in dose-related linear reductions in heart rate and cardiac output and linear increases in left heart filling pressure and systemic vascular resistance compared with saline-controlled measurements. The only statistically significant change at rest after pindolol was a small increase in the left heart filling pressure. The calculated systemic vascular resistance was increased after propranolol but unchanged after pindolol. During supine bicycle exercise the systolic blood pressure increased less after propranolol than after saline or pindolol. The increments in all other measured haemodynamic variables during exercise were equally influenced by the two drugs. Propranolol resulted in a significantly greater depression of the relationship between left heart filling pressure and cardiac output at rest and during exercise than an equivalent beta-blocking dose of pindolol. The contrasting haemodynamic profile of the two drugs is explicable by the partial agonist stimulation of the heart by pindolol directly maintaining left ventricular pumping activity and simultaneously lowering afterload by stimulating vasodilator beta2-adrenoceptors in peripheral arteriolar resistance vessels. In patients with impairment of left ventricular function due to coronary heart disease who require intravenous beta-blocking therapy, partial agonist activity in a beta-blocking drug may be haemodynamically advantageous.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 7-14 
    ISSN: 1432-1041
    Keywords: oxprenolol ; coronary heart disease ; normals ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration profile of oxprenolol after intravenous bolus injection, during intravenous infusion and following sustained oral administration was studied in a total of 106 patients with coronary heart disease. Speed of onset of pharmacodynamic activity, as measured by suppression of isoprenaline tachycardia, was discernible within a few seconds of central injection and complete within 5 min in all patients; variability in response was small. Following both i.v. bolus and intravenous infusion, plasma oxprenolol concentrations showed considerable between patient variability The plasma concentration/time profile observed in 16 patients following single intravenous oxprenolol bolus therapy was substantially higher, particularly during the early distribution phase, than observed and predicted volunteer data. Higher plasma oxprenolol concentrations were also attained during the more extended time sampling of the infusion studies; these findings would be compatible with reduced oxprenolol clearance in patients with ischaemic heart disease. During chronic oral therapy there was a many-fold between-subject variability in plasma concentration achieved following a given ingested dose. Correlation of antagonism of exercise tachycardia inhibition with plasma oxprenolol concentration in 15 male volunteers demonstrated near complete blockade of exercise stimulation of chronotropic beta-adrenoceptors at an average plasma oxprenolol concentration of 150 ng/ml. In coronary heart disease, such plasma concentrations can most conveniently be achieved by a 4 mg oxprenolol intravenous bolus with simultaneous infusion of 0.05 mg/kg/h; however, these studies provide sufficient information to allow alternative regimens to be derived should lesser plasma concentrations be considered desirable.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: nicardipine ; angina pectoris ; haemodynamic ; pharmacokinetics ; radionuclide studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic, haemodynamic and radionuclide studies explored the acute pharmacokinetic and pharmacodynamic actions of nicardipine in patients with coronary heart disease. Nicardipine infusion resulted in dose-related reductions in systolic and diastolic blood pressure and an increased heart rate. Pharmacodynamic activity was evident between 12 and 24 min following 5 and 10 mg i.v. nicardipine but by 3–6 min following the higher doses of 15 and 20 mg; hypotensive activity persisted for up to 2 h. Post-infusion nicardipine concentrations declined biexponentially; however the limited data precluded formal compartmental analysis. Plasma clearance ranged from 5–12 ml/min/kg, and appeared lower than previously reported volunteer data. The haemodynamic actions of nicardipine (10 mg infusion over 10 min) in 6 patients undergoing diagnostic catheterization were reductions in systolic, diastolic and mean systemic arterial pressure and systemic vascular resistance index. Heart rate and stroke volume index increased, and there was a small but statistically significant increase in pulmonary artery occluded pressure. Radionuclide parameters were measured in 20 patients with stable angina, at rest and during supine bicycle exercise, before and 3–5 min after nicardipine 10 mg intravenously. The left ventricular ejection fraction increased by 4% at rest but not during exercise. The left ventricular rest and exercise ejection and filling rates both increased with a concurrently reduced left ventricular ejection time. There was a highly significant inverse relationship between baseline exercise ejection fraction and the response to nicardipine; ejection fraction increased with low initial values but was either unchanged or fell with higher initial values. These data suggest that the acute effects of nicardipine in stable coronary artery disease probably reflect a reduction in left ventricular afterload and an associated augmentation of cardiac pumping performance. The acute circulatory profile of nicardipine appears sufficiently promising to warrant longer-term studies in ischaemic heart disease.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1619-1560
    Keywords: Finapres ; Non-invasive blood pressure ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p 〈 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p 〈 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p 〈 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (−6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p 〈 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p 〈 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.
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  • 8
    ISSN: 1619-1560
    Keywords: Finapres ; non-invasive blood pressure ; beta-adrenoceptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The blood pressure waveform is modified on distal propagation by phenomena such as dispersion, reflection and the state of the arterial compliance. The consequent effects are amplification and narrowing of the wave, with an increased systolic, reduced diastolic and essentially unaltered mean blood pressure. The Finapres measures the peripheral pressure using the volume clamp principle; it has not been validated under altered physiological conditions and during pharmacodynamic interventions. We studied simultaneous Finapres and brachial blood pressures (using a conventional oscillometric sphygmomanometer—Vitalmap) in ten normal volunteers at rest, and during dynamic exercise and a cold pressor test. The effects of pharmacodynamic intervention were examined following beta-adrenoceptor blockade with propranolol (160 mg) or beta-adrenoceptor modulation with the beta-adrenoceptor partial agonist celiprolol (400 mg). The Finapres systolic pressure was significantly higher than the brachial value during all three test states. The difference between the systolic pressures measured by the two devices was shown to increase significantly during the cold pressor test, but not during dynamic (supine bicycle) exercise. The Finapres diastolic pressure was significantly higher than the Vitalmap value during exercise and the cold pressor test. The differences between the two methods increased significantly over time. Beta-adrenergic blockade with propranolol or modulation with celiprolol had no significant interaction with the pressure differences between the Finapres and Vitalmap techniques. The results would support the view that the Finapres can provide blood pressure information which is robust under most circumstances. Although this pharmacodynamic intervention did not alter the relationship between the peripheral and central blood pressure, it is important to note that this dynamic relationship is sensitive to circulatory loading conditions and wave transmission characteristics; it is possible that the Finapres could be less reliable in clinical settings where potent vasoactive agents were being administered.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Clinical autonomic research 8 (1998), S. 145-153 
    ISSN: 1619-1560
    Keywords: heart rate variability ; Poincaré plot ; scatterplot ; nonlinear ; β-adrenoceptor ; agonist ; antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is evidence that the processes regulating heart rate variations reflect non-linear complexity and show ‘chaotic’ determinism. Data analyses using non-linear methods may therefore reveal patterns not apparent with conventional statistical approaches. We have consequently investigated two non-linear methods, the Poincaré plot (scatterplot) and cardiac sequence (quadrant) analysis, and compared these with standard time-domain summary statistics, during a normal volunteer investigation of an agonist and antagonists of the cardiac β-adrenoceptor. Under double-blind and randomized conditions (Latin square design), 12 normal volunteers received placebo, celiprolol (β2- and β2-adrenoceptor partial agonist), propranolol (β2- and β2-adrenoceptor antagonist), atenolol (β1- adrenoceptor antagonist) and combinations of these agents. Single oral doses of medication (at weekly intervals) were administered at 22∶30 h with sleeping heart rates recorded overnight. The long (SDNN, SDANN) and short-term (rmsSD) time-domain summary statistics were reduced by celiprolol — effects different from the unchanged or small increases after atenolol and propranolol alone. The Poincaré plot was constructed by plotting each RR interval against the preceding RR interval, but unlike previous descriptions of the method, an automated computer method, with a high level of reproducibility, was employed. Scatterplot length and area were reduced following celiprolol and different from the small increases after propranolol and atenolol. The geometric analysis of the scatterplots allowed width assessment (i.e. dispersion) at fixed RR intervals. Differences between the drugs were confined to the higher percentiles (i.e. 75% and 90% of scatterplot length: low heart rate). The long-term time-domain statistics (SDNN, SDANN) correlated best with scatterplot length and area whereas the short-term heart rate variability (HRV) indices (rmsSD, pNN50) correlated strongly with scatterplot width. Cardiac sequence analysis (differences between three adjacent beats; ΔRR vs ΔRR n+1) assessed the short-term patterns of cardiac acceleration and deceleration, four patterns are identified: +/+ (a lengthening sequencing), +/− or −/+ (balanced sequences), and finally −/− (a shortening sequence). A running count of events by quadrant, together with the average magnitude of the differences was computed. The β-adrenoceptor partial agonist celiprolol increased acceleration sequences. The duration of beat-to-beat difference shortened after celiprolol; this contrasted with increased duration of beat-to-beat difference after propranolol and atenolol. These results demonstrated a shift towards sympathetic dominance after the β-adrenoceptor partial agonist celiprolol contrasting with parasympathetic dominance after the β-adrenoceptor antagonists propranolol and atenolol. These non-linear methods appear to be valuable tools to investigate HRV in health and in cardiovascular disease and to study the implications of alterations in autonomic control during therapeutic intervention. Clin Auton Res 8:145–153
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  • 10
    ISSN: 1573-7241
    Keywords: heart rate variability ; scatterplot ; nonlinear ; beta-adrenoceptor ; partial agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is evidence that the processes regulating heart rate variability (HRV) reflect nonlinear complexity and show “chaotic” determinism. Data analyses using nonlinear methods may therefore reveal patterns not apparent with the standard methods for HRV analysis. We have consequently used two nonlinear methods, the Poincaré plot (scatterplot) and cardiac sequence (quadrant) analysis, in addition to the standard time-domain summary statistics, during a normal volunteer investigation of the effects on HRV of some agents acting at the cardiac beta-adrenoceptor. Under double-blind and randomized conditions (Latin square design), 25 normal volunteers received placebo, salbutamol 8 mg (β2-adrenoceptor partial agonist), pindolol 10 mg (β2-adrenoceptor partial agonist), or atenolol 50 mg (β1-adrenoceptor antagonist). Single oral doses of medication (at weekly intervals) were administered at 22:30 hours, with sleeping heart rates recorded overnight. The long-term (SDNN, SDANN) and short-term (rMSSD) time-domain summary statistics were reduced by salbutamol 8 mg and increased by atenolol 50 mg compared with placebo. The reductions in both SDNN and SDANN were greater after salbutamol 8 mg compared with pindolol 10 mg. The reduced HRV after pindolol 10 mg differed from the increased HRV following atenolol 50 mg. The Poincaré plot, constructed by plotting each RR interval against the preceding RR interval, was measured using a reproducible computerized method. Scatterplot length and area were reduced by salbutamol 8 mg and increased by atenolol 50 mg compared with placebo; scatterplot length and area were lower after pindolol 10 mg compared with atenolol 50 mg. Geometric analysis of the scatterplots allowed width assessment (i.e., dispersion) at fixed RR intervals. At the higher percentiles (i.e., 90% of scatterplot length: low HR), salbutamol 8 mg reduced and atenolol 50 mg increased dispersion; at lower percentiles (i.e., 10%, 25%, and 50% length), atenolol 50 mg and pindolol 10 mg increased dispersion compared with placebo and salbutamol 8 mg. Cardiac sequence analysis (differences between three adjacent beats; ΔRR vs. ΔRRn+1) was used to assess the short-term patterns of cardiac acceleration and deceleration. Four patterns were identified: +/+ (a lengthening sequencing), +/− or −/+ (balanced sequences), and finally −/− (a shortening sequence). Cardiac acceleration episodes (i.e., number of times ΔRR and ΔRRn+1 were both changed) were increased in quadrants −/− and +/+ following pindolol 10 mg and salbutamol 8 mg; the beat-to-beat difference (ΔRRn+1) was reduced after salbutamol 8 mg compared with the three other groups. These results demonstrated a shift towards sympathetic dominance (β-adrenoceptor partial agonist salbutamol 8 mg) or parasympathetic dominance (β1-adrenoceptor antagonist atenolol 50 mg); pindolol 10 mg exhibited HR-dependent effects, reducing HRV at low but increasing variability at high prevailing heart rates. These nonlinear methods appear to be valuable tools to investigate HRV in health and to study the implications of perturbation of HRV with drug therapy in disease states.
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