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  • 1
    ISSN: 1435-1803
    Keywords: cimetidine ; ranitidine ; quinidine ; pro-arrhythmic ; programmed stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Seven to 28 days after coronary artery ligation, programmed electrical stimulation was performed in conscious dogs. Groups of 6 previously inducible dogs in which no arrhythmia could presently be achieved were randomly allocated to reccive quinidine, cimetidine, ranitidine or placebo. Results were assessed for the drugs' ability to induce ventricular tachycardia or fibrillation, and compared with placebo using Fisher's Exact Test. In the placcbo group 4/6 dogs remained unchanged, one developed an arrhythmia, and one died. With quinidine, 3/6 dogs developed an arrhythmia (0.5 mg/kg, 4.0 mg/kg, 4.0 mg/kg) and three died (4 mg/kg, 8 mg/kg, 16 mg/kg) (p〈0.05 compared with placebo). With cimetidine, 4/6 dogs remained unchanged, one developed an arrhythmia after 4 mg/kg, and one died after 0.5 mg/kg. After ranitidine 3/6 dogs remained unchanged and three died (1.0 mg/kg, 4.0 mg/kg, 16.0 mg/kg). PR, QTc, QRS, refractory periods, and mean systolic pressure remained unchanged after placebo, cimetidine, and ranitidine, but QTc increased (p〈0.05) and mean systolic pressure fell (p〈0.01) after quinidine. Heart rate did not change following placebo, but increased (p〈0.05) after each of the three drug treatments. These results fail to show a significant arrhythmogenic effect of cimetidine or ranitidine in a model validated by the significant pro-arrhythmic effects of quinidine. The cause of death in all cases was ventricular fibrillation.
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  • 2
    ISSN: 1432-1041
    Keywords: propranolol ; atenolol ; baroreflex function ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute administration of the β-adrenoceptor antagonists propranolol (80 mg) and atenolol (50 mg) on baroreflex function were investigated in healthy volunteers. Two h after administration both propranolol and atenolol significantly prolonged the supine R-R interval (1126, 1128 ms respectively) compared to placebo (1012 ms); systolic arterial pressure also fell (102.9, 102.0 mm Hg respectively) compared to placebo (112.6 mm Hg). Baroreflex function, assessed using glyceryl trinitrate to deactivate the baroreceptors was unchanged by these drugs compared to placebo. Baroreflex sensitivity (slope of the linear regression line relating R-R interval to systolic blood pressure) using phenylephrine to activate the baroreceptors, was also unchanged (17.2, 17.9 ms/mm Hg respectively) compared to placebo (19.9 ms/mm Hg). However both regression lines were shifted (p〈0.05) to the left compared to placebo.
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  • 3
    ISSN: 1741-0444
    Keywords: Alignment technique ; Coherent averaging ; Computer simulation ; High-frequency ECG ; Late potentials ; Noise ; Signal-averaged ECG ; Trigger jotter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The process of QRS alignment as required in signal-averaged ECG can impose serious limitations on the spectral range of the signal output. This effect depends basically on the particular alignment technique being used and on the level and type of noise present in the recorded ECG. In clinical studies where a wide-band (1000 Hz) ECG averager is required, the conventional QRS alignment technique, based on maximum coherence matching (MCM) with a template beat, may not perform consistently well. An alternative QRS alignment technique based on the accurate detection of a single fiducial point (SFP) in the bandpass filtered (3–30 Hz) QRS complex was developed. Using computer simulation methods, a comparative assessment of the frequency bandwidths (3 dB points) offered by both MCM and SFP techniques as a function of noise level (15–100 μ RMS) and type (EMG and 50 Hz interference), was carried out. The results of the comparative assessment indicated a better performance by the SFP technique in all cases of noise. Hence, the SFP technique would perform more reliably for high-frequency analysis of a noisy ECG, especially when 50 Hz interference is high. Furthermore, SFP is considerably faster than MCM (about four times) when implemented digitially, and its analogue realisation is feasible. The SFP technique is suitable for late-potential analysis in the signal-averaged ECG.
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  • 4
    ISSN: 1432-1041
    Keywords: digoxin ; therapeutic range ; intuitive prescribing ; prescribing aid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 37 patients on maintenance digoxin therapy were observed in hospital over an 8 day period. From day 1 to day 8 measurements of plasma digoxin and serum creatinine indicated that these patients were in the equilibrium state with regard to digoxin levels and renal function. Assuming a linear relationship between dose and plasma concentration, it was possible to calculate the doses which would have produced plasma concentrations of 1.5 ng/ml, and at the limits of the ‘usual therapeutic range’, 0.8 and 2.0 ng/ml. Doses obtained from six prescribing aids and those prescribed intuitively by the doctor were then compared. None of the methods used would have resulted in plasma digoxin concentrations within the ‘usual therapeutic range’ in more than 57% of the patients. The physicians' intuitive choice appeared to be better than the doses estimated from prescribing aids, in that they were correct as often as any assisted method, and when wrong tended to prescribe ‘too low’ rather than ‘too high’. The prescribing aids tended to overestimate dosage in many patients, as high as 65% with one. Plasma digoxin concentration measurement would appear to be the only way to ensure adequate therapeutic efficacy and avoid toxicity in patients receiving maintenance digoxin.
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  • 5
    ISSN: 1432-1041
    Keywords: methoxamine ; alpha-methyl-noradrenaline ; propranolol ; baroreceptor function ; Valsalva's Manoeuvre
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Methoxamine and α-methyl-noradrenaline were administered to six healthy male subjects on separate days as rapid bolus injections until blood pressure increased by approximately 30 mmHg; Valsalva's Manoeuvre was carried out on each occasion. Propranolol (80 mg) or placebo was administered (random order, double-blind, weekly intervals) and the observations were repeated after 2 h. Baroreceptor sensitivity (ΔR-R interval ms/mmHg systolic BP) was less (p〈0.05) with α-methyl-noradrenaline than methoxamine. Propranolol abolished the differences in baroreceptor-mediated bradycardia following α-methyl-noradrenaline and methoxamine, and shifted the baroreceptor sensitivity regression lines (p〈0.05) to the left. During the release phase of Valsalva's Manoeuvre baroreceptor sensitivity was increased following propranolol. The smaller baroreceptor-mediated bradycardia response observed with α-methyl-noradrenaline does not support the hypothesis that pre-synaptic α-adrenoceptors have a physiological role in the modulation of baroreceptor function in man, and may be due to α-methyl-noradrenaline having β1-agonist activity.
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  • 6
    ISSN: 1432-1041
    Keywords: alfuzosin ; prazosin ; alpha1-adrenoceptor antagonist ; noradrenaline ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open dose ranging study with random inclusion of placebo, alfuzosin (α1-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin. Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, tmax ranged from 1–2 h; Cmax (4.1 to 20.8 ng · ml−1; AUC (0–24) 20 to 132 ng · ml−1 · h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation. A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4. Supine plasma noradrenaline increased with alfuzosin and prazosin at 2 and 4 h on Days 1 and 4; the increases were not significantly different. The plasma elimination half-life (t1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t1/2) for prazosin was 2.6 and 2.9 h. In conclusion alfuzosin causes small reductions in systolic blood pressure, accompanied by a dose dependent increase in heart rate in the supine and standing position and following exercise.
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  • 7
    ISSN: 1432-1912
    Keywords: Bezold-Jarisch reflex ; Baroreceptor reflex ; Alpha agonists ; CNS-Facilitation ; Alpha antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Bezold-Jarisch reflex characterized by hypotension and bradycardia was elicited in anaesthetized artificially respired dogs (pretreated with a beta-adrenoceptor antagonist) using capsaicin 10 μg/kg (i.v.). Intracisternal administration of the highly selective “clonidine-like” alpha2 adrenoceptor agonists B-HT 920 (10 μg/kg) or B-HT 933 (30 μg/kg) significantly facilitated this reflex bradycardia. The involvement of central alpha2-adrenoceptors is suggested as intracisternal administration of the alpha2 adrenoceptor blocking drugs yohimbine (50 μg/kg) and piperoxan (50 μg/kg) antagonized this facilitation. B-HT 920 also facilitated the vagally mediated baroreceptor reflex to the hypertensive effect of intravenous noradrenaline (3 μg/kg). Although the Bezold-Jarisch reflex and the baroreceptor reflex have different afferent pathways, both reflexes may either converge into a common pathway or have separate neuronal chains within the medulla; however, this study indicates that both have a similar central modulatory system stimulated by alpha2 adrenoceptors.
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  • 8
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The relationship between plasma and myocardial digoxin concentrations was investigated in hypoxic and nonhypoxic dogs. The results indicate that hypoxic dogs have lower plasma levels, higher myocardial levels, and an altered myocardial distribution when compared to non-hypoxic dogs.
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  • 9
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A study was made of the effect of activated dimethicone on the absorption of digoxin in relation to other commonly used antacid constituents using an in vitro experimental model. Dimethicone was found not to affect the absorption of digoxin in relation to aluminium hydroxide, bismuth carbonate, light magnesium carbonate and magnesium trisilicate whose effects on the absorption of digoxin were in agreement with values reported in the literature.
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  • 10
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A study was made of the effect of 4 constituents of antacid preparations on the absorption of the coumarin derivate warfarin sodium using an in vitro experimental model. The constituents tested were activated dimethicone (a silicone) magnesium trisilicate, bismuth carbonate and the adsorbant, kaolin. Slight decreased intestinal absorption was shown by magnesium trisilicate (19%) and bismuth carbonate (7%), the other 2 components showing no effects.
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