Effect of treatment of hypertension in the primary preventive trial, Goteborg, Sweden.
(9/17)
1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two groups did not differ with respect to age, smoking habits or cholesterol values, but screening BPs were higher in the treatment group. 3 During 4.3 years' follow-up there was a significantly lower total death rate in the treatment group compared with reference group. 4 There was also a strong tendency towards lower incidence of non-fatal myocardial infarction (P = 0.06). The pooled incidence of non-fatal myocardial infarction and fatal CHD was lower in the treatment group than in the reference group (P less than 0.03). (+info)
A comparison of the effects of bethanidine, meobentine and quinidine on the electrical activity of rat hearts in vivo and in vitro.
(10/17)
Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments of the right ventricular free wall of the rat heart during superfusion and electrical stimulation in vitro at 37 degrees C. The sulphates of bethanidine, meobentine or quinidine (4 to 20 microM) applied in vitro caused a prolongation of action potential duration and a delayed and slowed return of electrical excitability following an action potential. Intracardiac electrical stimulation of the urethane-anaesthetized rat heart in situ was used to measure ventricular refractory periods from the electrocardiogram. Intravenous administration of bethanidine, meobentine or quinidine (10 to 20 mg kg-1) caused a prolongation of ventricular refractory periods. Quinidine had a briefer duration of action than either of the other two drugs tested. Urethane-anaesthetized open-chested rats which were subjected to left coronary artery occlusion displayed ventricular tachyarrhythmias in their electrocardiogram. These arrhythmias occurred during the period of occlusion and even more prominently after release of the occlusion. Intravenous administration of bethanidine, meobentine or quinidine (1 to 20 mg kg-1) protected rats against these arrhythmias. The protective effect of quinidine was briefer than that of either of the other two drugs tested. (+info)
Central alpha- and beta-adrenoceptors modifying arterial blood pressure and heart rate in conscious cats.
(11/17)
1 In conscious unrestrained cats noradrenaline, alpha-methylnoradrenaline and clonidine, infused into the lateral cerebral ventricles (i.c.v.) caused dose-related falls in blood pressure and heart rate; both effects were abolished after i.c.v. phentolamine.2 In 12 out of 20 cats, i.c.v. isoprenaline and salbutamol when given caused dose-related pressor responses and tachycardias. These effects were abolished after i.c.v. beta-adrenoceptor blocking drugs but were unaffected by alpha-adrenoceptor blocking agents.3 In 5 out of 20 cats, i.c.v. isoprenaline regularly produced dose-related falls in blood pressure with associated tachycardias; both effects were abolished after i.c.v. beta-adrenoceptor blocking agents.4 Intracerebroventricular dopamine produced cardiovascular responses which were qualitatively similar to those produced by i.c.v. isoprenaline.5 Intracerebroventricular adrenaline produced complex responses in untreated animals but typical alpha-effects were obtained after prior i.c.v. treatment with a beta-adrenoceptor blocking agent and typical beta-effects after i.c.v. pretreatment with an alpha-adrenoceptor blocking agent.6 The cardiovascular changes produced by i.c.v. beta-adrenoceptor agonists were abolished after systemic administration of hexamethonium or bethanidine.7 The results are discussed in the light of the mode of action of beta-adrenoceptor stimulants and beta-adrenoceptor blocking agents in the treatment of hypertension. (+info)
Possible role of brain norepinephrine in the hypothalamic hypophyseal adrenal system.
(12/17)
Intracisternal injection of bethanidine in rats decreased brain norepinephrine turnover without affecting its endogenous level, and increased both cardiac norepinephrine turnover and serum corticosterone level. A negative correlation was observed between brain norepinephrine turnover rate and serum corticosterone level. On the other hand, when cardiac norepinephrine turnover was suppressed by intraperitoneal injection of bethanidine, serum corticosterone did not change significantly. Next, ether inhalation was added after intracisternal injection of bethanidine. Then, serum corticosterone increased more even brain norepinephrine turnover was suppressed only slightly. These data may indicate that serum corticosterone increases by selective decrease in brain norepinephrine turnover via the humoral route; from the hypothalamus down to the adrenal cortex. Inversely, intracisternal injection of corticosterone increased brain norepinephrine turnover. These results suggest that brain norepinephrine may play an inhibitory role in the tonic regulation of CRF-ACTH secretion in the higher center than the hypothalamus and there may be a closed-loop feedback system between brain norepinephrine and serum corticosterone. (+info)
A comparison and an investigation of a potential synergistic effect of labetalol and bethanidine in patients with mild hypertension.
(13/17)
1 The effects of labetalol, bethanidine and combined treatment with both drugs were compared in a within-patient randomized cross-over study in mild essential hypertension. Attention was directed to whether or not labetalol and bethanidine differed in their pattern of effect on arterial BP and whether evidence of synergism was apparent. 2 At the doses used labetalol significantly lowered systolic and diastolic BPs and heart rate lying, sitting, standing and after exercise. The dose of bethanidine used did not affect heart rate significantly while lowering systolic and diastolic BPs only after exercise and less clearly on standing. Combined treatment lowered BPs on standing and after exercise and heart rate after exercise. 3 The type and frequency of side-effects were similar with bethanidine and labetalol but were much less with combined treatment. 4 No evidence of synergism was observed. (+info)
Determination of bethanidine in plasma by liquid-chromatography with a microbore reversed-phase column.
(14/17)
In this novel method for quantifying bethanidine in plasma, after a multi-step extraction of bethanidine and internal standard from 2.0 mL of plasma, the drugs are separated on a "microbore" C18 reversed-phase column and quantified by their ultraviolet absorbance at 210 nm. The isocratic chromatographic separation takes about 15 min with use of an ion-pairing regent in the mobile phase (acetate buffer/acetonitrile, 9/1 by vol) and a flow rate of 0.25 mL/min. Sensitivity is increased relative to conventional columns, and solvent consumption is reduced by 90%. The standard curve is linear to at least 5 mg/L, and the detection limit is 0.02 mg/L. The within-run precision of the method is excellent (CV 4%) at a midrange concentration of 1.25 mg/L. (+info)
Life threatening ventricular tachycardias in late survivors of surgically corrected tetralogy of Fallot.
(15/17)
Electrophysiological tests were performed in three patients with surgically corrected tetralogy of Fallot (mean age at evaluation 25 years, mean age at surgical correction 4 years) who had had either a cardiac arrest or transient neurological disturbances (presyncope, syncope) associated with ventricular arrhythmias. All three patients had an excellent haemodynamic result from surgery as judged by echocardiography and cardiac catheterisation. Ambulatory electrocardiographic monitoring and stress exercise testing were normal in two patients and showed complex ventricular ectopy in one. During invasive electrophysiological evaluation all three patients had inducible ventricular tachycardia (monomorphic QRS in two patients, cycle lengths 230 and 240 ms; polymorphic QRS in one patient, mean cycle length 200 ms) with adverse haemodynamic effects in all three patients. These findings suggest that rapid ventricular tachycardia with detrimental haemodynamic consequences, similar to that induced during laboratory study, was the basis for the presenting symptoms in each patient. This possibility was confirmed in one patient who had identical QRS morphology during both spontaneous ventricular tachycardia and that induced during the laboratory study. Thus sudden death or symptoms of syncope postoperatively in patients with surgically corrected tetralogy of Fallot appear to be due to rapid ventricular tachycardia, which may occur despite an apparently excellent surgical result. (+info)
Evaluation of drug-induced changes in myocardial repolarisation using the paced evoked response.
(16/17)
The use of the pace evoked response system in the assessment of drug-induced changes in myocardial repolarisation is reported. Using a conventional pacing electrode lead for both pacing and sensing, this system records the dominantly local repolarisation which follows a controlled (paced) depolarisation from the same site. Measurements of the latency of the ventricular evoked response at matched heart rates before and after drug administration permit the accurate direct comparison of the effects of drugs with class 3 mode of action on cardiac muscle repolarisation. Using this method we have evaluated the effect on the timing of the evoked T wave of two drugs which are known to prolong phase 2 of the action potential. Intravenous amiodarone (5 mg/kg) prolonged the stimulus-peak evoked T wave interval by an average of 39-4 ms (15% of control values); three hours after oral bethanidine (2 mg/kg) this interval increased by an average of 25.8 ms (10% of control values). The effect of therapeutic interventions on the latency of the local paced evoked response provides a simple, accurate assessment of their effect on the cellular action potential duration and constitutes a new tool in electrophysiological investigations. (+info)