Decrease in the sensitivity to the anti-ischemic effect of propranolol and prospects for correcting it in patients with stable angina pectoris

AIM: To study incidence of low sensitivity to an antiischemic effect of propranolol and feasibility of its correction with a metabolic drug--trimetazidine. MATERIAL AND METHODS: Paired treadmill and bicycle exercise tests were made until depression of segment ST > 1 mm and a typical angina episode. The trial included 147 men with ischemic heart disease, stable angina pectoris (functional class II-III). The antiischemic effect of propranolol single doses 40 or 80 mg were assessed in 117 patients. Single doses of propranolol 40 mg, trimetazidine 20 mg and their combination were examined for an antiischemic effect in 30 patients. The absence of the above effect of propranolol was stated in 20 patients who participated in a double blind, randomised, placebo-controlled study with conduction of 2-week courses of regular administration of propranolol in a dose 120 mg/day, trimetazidine 60 mg/day and their combination. Echo-CG was made initially and in the end of each course. RESULTS: Propranolol's antiischemic effect of a single dose 40 mg was not found in 45.3% patients, 40-80 mg--in 21%. Among 20 patients without effect of the single propranolol dose, an increment of the threshold load made up 20.7 +/- 15.7 s, after intake of trimetazidine 16.3 +/- 18.6 s. The combination of these drugs significantly increases the increment of the threshold load duration to 90.8 +/- 80.4 s. The same picture was observed in the course treatment. The above increment in the course administration of propranolol was 46.3 +/- 15.3 s, of trimetazidine 22.8 +/- 20.2 s, of their combination 122.7 +/- 21.8 s (p = 0.02). In the absence of propranolol effect, echo-CG registered deterioration of disorder of left ventricular diastolic function. 10 patients with effect of the single propranolol dose this deterioration was not observed in combined use of propranolol and trimetazidine. CONCLUSION: The antiischemic effect of propranolol in a single dose 40 mg was not recorded in about half of the examined anginal patients. Combined use of propranolol and trimetazidine in cases with no propranolol effect provides a synergetic effect both in single and course administration.     

The effects of verapamil and propranolol on exercise tolerance in hypertensive patients

In a single-blind, placebo-controlled crossover study the effects of verapamil (450 +/- 30 mg/day) and propranolol (160 +/- 20 mg/day) on endurance time during submaximal exercise were compared in eight patients with essential hypertension. The drugs were given in randomized order. Each active drug period was preceded by a placebo phase. Endurance tests were performed during both placebo periods and treatment with verapamil and propranolol by bicycle ergometry. Both drugs were equally effective in decreasing resting blood pressure. Verapamil and propranolol reduced exercise heart rate, the effect of propranolol being more pronounced. With placebo, endurance time during exercise was 57 +/- 11 minutes; with propranolol it was 32 +/- 7 minutes (P less than 0.05). Verapamil had no influence on endurance time. The study demonstrates that in contrast to propranolol, verapamil has no influence on exercise tolerance during submaximal work in patients with hypertension.     

Sublingual Flunarizine: a New Effective Management of the Migraine Attack. A Comparison versus Ergotamine

SYNOPSIS
Flunarizine was found to be effective in the acute treatment of isosorbide dinitrate induced migraine attacks, when given in a dosage of 10 mg sublingually.
The present study consists of two parts: in the first preliminary investigation, 7 out of 8 migraine patients who developed a typical migraine attack after isosorbide dinitrate were relieved of pain within about 10 minutes. On the basis of this result a second, randomized controlled open trial was performed, in which the acute efficacy of flunarizine was compared with ergotamine tartrate, 0.25 mg i.m., on 40 migraine patients. Flunarizine was found as effective as ergotamine (75% positive responses in the flunarizine group, 70% in the ergotamine group). The mean latency of the flunarizine effect was significantly lower than that of the ergotamine ( r < 0.001, Student's t test). Moreover sublingual flunarizine was found to be virtually devoid of side effects.     

A double-blind comparison of acebutolol (Sectral) and propranolol (Inderal) in the treatment of hypertension in black Nigerian patients

Acebutolol and propranolol were compared in forty-five Black African patients in a double-blind randomized trial carried out at Ahmadu Bello University Teaching Hospital in Kaduna, Nigeria. After a wash-out period of 6 weeks, including placebo administration for the last 4 of those weeks, twenty-seven patients were given acebutolol once daily and eighteen were given propranolol twice daily for 12 weeks, followed by a tapering-off period of 2 weeks, making a total of 14 weeks on active treatment. The two beta-receptor blocking drugs were effective in controlling hypertension with final daily doses ranging from 160 to 320 mg in the propranolol group and 400 to 800 mg in the acebutolol group. The supine systolic blood pressure responses with acebutolol were statistically significant and better than those elicited by propranolol. Acebutolol produced less (resting) bradycardia than did propranolol; this may be related to acebutolol's intrinsic sympathomimetic activity. The only unpleasant side-effects reported in this study were slight dizziness in two patients treated with propranolol and slight tiredness in one patient treated with acebutolol. No significant abnormal changes were noted in laboratory tests or chest X-rays. Electrocardiography detected supraventricular tachyarrythmia in five patients: this disappeared by the end of the study. Acebutolol was shown to be a safe, effective and reliable antihypertensive drug, at least comparable to and probably slightly better than, propranolol in the treatment of hypertension in Black Nigerians. It has the added advantage of a once-daily dose schedule.     

Medical management of angina pectoris.

Nitroglycerin should be the first agent prescribed for patients with angina pectoris. When nitroglycerin is used daily, a trial with longer-acting nitrates (eg, isosorbide dinitrate) is warranted. If angina persists, use of beta-adrenergic blocking agent (propranolol) should be considered. Appropriate use of nitrates and propranolol, singly or in combination, will relieve angina pectoris due to coronary heart disease in most patients.     

Comparative study of isosorbide dinitrates and mononitrates in patients with ischemic heart disease and stable angina pectoris caused by stenosing coronary atherosclerosis

In an open clinical trial 19 patients with angina pectoris (functional class II-III) received in turn either non-retard tablets of isosorbide dinitrate (nitrosorbid, cardiket) in a mean dose 80 mg/day or isosorbide 5-mononitrate (mono mac) in a mean dose 51.5 mg/day. Each drug was given for a month. The effect was assessed by changes in frequency of anginal attacks and exercise tolerance. Non-retard isosorbide dinitrate and isosorbide 5-mononitrate demonstrate a good antiischemic effect, are safe and well tolerated. Isosorbide dinitrate and mononitrates do not differ significantly in reduction of the anginal attacks and by an increase in exercise tolerance but the effective dose of mono mac was 1.5-2 times less than that of nitrosorbide or cardiket, thus it is more cost-effective.     

Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily

This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe.     

Propranolol attenuates exercise-induced increment in human lymphocytic beta-adrenergic receptors

The effect of peroral propranolol administration on the level of lymphocytic beta-adrenergic receptors was studied in six healthy volunteers using an acute exercise test. When no drug was used, a 15-min ergometer exercise period induced a significant increase in the receptor density (from 42 +/- 5 to 117 +/- 14 fmol/mg protein; mean +/- SEM), followed by a return to the pre-exercise level after a 1-hr rest. During propranolol administration (40 mg, three times daily), the basal receptor level (49 +/- 4 fmol/mg protein) did not change but the exercise-induced increment of the receptor density was significantly inhibited (peak value 79 +/- 5 fmol/mg protein, p less than 0.05). This effect could not be explained by direct competition for receptor binding sites by propranolol nor by differences in the plasma adrenalin and noradrenaline concentrations during the two tests. The fact that propranolol interferes with the normal adaptation of the beta-adrenergic receptor level to acute exercise may explain some of the adverse effects of beta-blocking drugs on physical performance.     

Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade.

To investigate the mechanisms of ventricular arrhythmia suppression by propranolol, we determined the antiarrhythmic efficacy of d-propranolol in 10 patients with frequent ventricular ectopic depolarizations (VEDs) and nonsustained ventricular tachycardia. After an initial placebo phase, 40 mg d-propranolol was administered orally every 6 h with dosage increased every 2 d until arrhythmia suppression (greater than or equal to 80% VED reduction), intolerable side effects, or a maximal dosage (1,280 mg/d) was reached. Response was verified by documenting return of arrhythmia during a final placebo phase. Arrhythmia suppression occurred in six patients while two more had partial responses. Effective dosages were 320-1,280 mg/d (mean 920 +/- 360, SD) of d-propranolol with corresponding plasma concentrations of 60-2,280 ng/ml (mean 858 +/- 681). For the entire group, the QTc interval shortened by 4 +/- 4% (P = 0.03). Arrhythmia suppression was accompanied by a reduction in peak heart rate during exercise of 0-29%. To determine whether arrhythmia suppression could be attributed to beta-blockade, racemic propranolol was then administered in dosages producing the same or greater depression of exercise heart rate. In 3/8 patients, arrhythmias were not suppressed by racemic propranolol indicating that d-propranolol was effective via a non-beta-mediated action. By contrast, in 5/8 patients racemic propranolol also suppressed VEDs. We conclude that propranolol suppresses ventricular arrhythmias by both beta- and non-beta-adrenergic receptor-mediated effects.     

Dose-Related Hepatic Blood Flow Effects Differentiate Nicorandil, Hydralazine, and Isosorbide Dinitrate in Healthy Subjects

Dose response on hepatic blood flow of nicorandil (2.5, 5, and 10 mg), isosorbide dinitrate (5, 15, and 40 mg), and hydralazine (10, 25, and 50 mg) was assessed in 18 healthy subjects (6 per drug) using a three-period crossover design. Indocyanine green clearance was used to estimate hepatic blood flow before and at two timepoints after dosing. Greater hepatic blood flow changes occurred 90 (than 30) min after nicorandil and isosorbide dinitrate, and 60 (than 150) min after hydralazine. Nicorandil (mixed vasodilator) decreased hepatic blood flow by minus sign13 plus minus 4% (p < 0.05), minus sign15 plus minus 7%, and minus sign21 plus minus 6% (p < 0.05) (mean plus minus standard error of the mean) after 2.5, 5, and 10 mg, respectively; blood pressure was not reduced and heart rate was unchanged. Individual changes correlated poorly with plasma nicorandil concentrations. Isosorbide dinitrate (predominant venodilator) decreased hepatic blood flow by minus sign23 plus minus 9%, minus sign27 plus minus 5% (p < 0.05), and minus sign26 plus minus 7% (p < 0.05) after 5, 15, and 40 mg, respectively; blood pressure decreased (8--12 mm Hg) and heart rate increased (8 beats min(minus sign1)). Hydralazine (arterial dilator) increased hepatic blood flow by 29 plus minus 16%, 32 plus minus 11% (p < 0.05), and 33 plus minus 26% after 10, 25, and 50 mg, respectively; blood pressure was unchanged and heart rate increased (16 beats min(minus sign1)). Hepatic vascular resistance increased after nicorandil and isosorbide dinitrate but decreased after hydralazine. As assessed by hepatic blood flow response, nicorandil behaves more like a predominant venodilator than a direct arterial dilator. Dose and time variables were important to understanding the overall hemodynamic profile of each drug.     

Propranolol-hydralazine combination in essential hypertension

The efficacy of a propranolol-hydralazine combination tablet was compared with that of each of its two components in the twice-daily treatment of mild to moderate essential hypertension (diastolic blood pressure: 100 to 125 mmHg). After a three-week, single-blind, placebo period, a 9- to 18-week, single-blind, dose-finding phase with the combination was performed. The daily doses of propranolol/hydralazine were 40 mg/25 mg, 80 mg/25 mg, 80 mg/50 mg, 120 mg/50 mg, 160 mg/50 mg, and 160 mg/100 mg. Of 83 patients, 73 (88%) had decreases in diastolic blood pressure equal to or greater than 10 mmHg. Thirty-eight (46%) patients had a diastolic blood pressure equal to or less than 90 mmHg while taking 80 mg propranolol/50 mg hydralazine or less given BID. Mean systolic and diastolic pressures were reduced by 16.8 mmHg (10.9%) and 17.6 mmHg (16.7%), respectively (P less than 0.001). A ten-week, double-blind, parallel-treatment phase followed in which patients were randomly assigned to the combination tablet or to propranolol or hydralazine. There were significantly larger increases in mean systolic (P less than 0.01) and mean diastolic (P less than 0.03) blood pressure when the components were taken alone than with the combination from the mean of the last three weekly dose-finding visits to the mean of the last four biweekly parallel-treatment visits. The changes in systolic/diastolic blood pressures were: hydralazine (n = 30), 14.43/8.62 mmHg; propranolol (n = 24), 9.87/6.09 mmHg; and the combination (n = 27), 1.47/1.53 mmHg. During the parallel-treatment phase, the proportions of patients with new complaints were: hydralazine, 16/31 (52%); propranolol, 10/25 (40%); and the combination, 11/27 (41%). In the hydralazine group, three patients had cardiovascular events (severe tachycardia, mild palpitations, and skipped heart beats) and two patients had mild anxiety; no such occurrences were noted in the propranolol or combination group. The mean change (increase) in heart rate from the end of dose-finding to the end of the double-blind period was significantly larger for patients taking hydralazine than for patients taking propranolol or the combination. Mean changes for these groups were: hydralazine, 12.4 beats/min; propranolol, 2.9 beats/min; and the combination, 1.8 beats/min (P = 0.0001). This study found the combination of propranolol plus hydralazine to be safe and more effective than either component.     

Cost-effect clinical analysis in choice of methods of coronary heart disease diagnosis

AIM: To select optimal methods of coronary heart disease (CHD) diagnosis in patients with different CHD probability using cost-effect analysis. MATERIAL AND METHODS: The trial included 102 patients admitted to hospital because of suspected CHD. The initial CHD probability was determined according to G.A. Diamond table. CHD diagnosis was made with application of Holter ECG monitoring (88 patients), treadmill test (67 patients), dobutamine stress echocardiography (echo-CG, 31 patients), stress single photon emission computed tomography (SPECT, 30 patients), multislice computed tomography (MSCT) with contrast study of coronary arteries (14 patients). Non-invasive tests were followed by coronaroangiography. The cost-effect method was used for analysis of the above methods cost efficacy. RESULTS: MSCT specificity was 96%, specificity of the other methods - 70-75%. SPECT was most sensitive (96%), Holter ECG monitoring was the least sensitive (49%). Efficacy of all the diagnostic tests was maximal in moderate probability of CHD. In spite of its moderate specificity and sensitivity, treadmill test was the cheapest and, therefore, most cost effective in all the groups. Specification of CHD probability by 1% required 17.4 roubles in low risk groups, 9.4 and 24.7 roubles in moderate and high risk, respectively. CONCLUSION: CHD diagnosis should be started with treadmill test.     

Treatment of Chronic Ventricular Dysrhythmias in the Young

The decision to treat chronic ventricular dysrhythmias in o young patient is based upon the potential for eJectrophysioIogic or hemodynamic instability. We have treated 51 young patients (mean age 13.4 years; range 1 week to 30 years) with chronic ventricular dysrhythmias according to the following guidelines: multiform premature ventricular contractions (PVCs), couplets and ventricular tachycardia were treated in all patients; frequent uniform PVCs were treated in patients with an abnormal heart. All patients were admitted to the hospital and continuous 24-hour electrocardiograms (ECGs) were performed. Drug serum concentrations were measured every six hours. A drug was considered “effective” if there were less than 10 uniform PVCs per hour. Drug dosages were increased until clinical signs of mild toxicity developed or the serum concentration was above the therapeutic range. Drug treatment was begun in each patient with phenytoin: 32 received an oral loading dose and 19 an intravenous loading dose. If this was ineffective, other drugs were added or substituted: propranolol, quinidine sulfate and disopyra-mide. Patients were divided into three groups according to their hemodynamics. The ages and types of ventricular dysrhythmias were similar for the three groups. Group I had 25 patients with severely abnormal hemodynamics; drugs were effective in 92%. Group II had 22 patients with moderately abnormal hemodynamics; drugs were effective in 68%. Group III had four patients with normal hemodynamics; drugs were effective in 50%. Phenytoin was the most effective drug in 39/51 (76%) followed by propranolol in 3/7 (43%) and quinidine in 1/7 (14%). We conclude: (1) chronic ventricular dysrhythmias can be controlled in 76% of children with standard drug regimens. (2) The response to drugs was significantly related to hemodynamic status: the most effective control was in patients with severely abnormal hemodynamics and the least effective was in patients with a normal heart. (3) Phenytoin is the drug of choice for children with ventricular dysrhythmias, especially those with abnormal hemodynamics. (PACE, Vol. 4, November-December, 1981)     

Pathophysiologic and pharmacokinetic determinants of the antihypertensive response to propranolol.

The tendency for patients with essential hypertension to differ markedly in antihypertensive response to propranolol could arise from pathophysiologic or pharmacokinetic differences between them. This possibility was investigated in 23 men with mild to moderately severe essential hypertension. At each of three propranolol doses, 40 mg, 80 mg, and 320 mg daily, approximately a 20-fold range in steady-state plasma propranolol concentrations was observed. Clinical response however was unrelated to plasma propranolol: oral dose ratio, since patients with higher plasma levels were less sensitive to the existing plasma drug concentration. When falls in blood pressure and plasma propranolol concentration were compared overall, a biphasic dose-response relationship was noted, with a first component at plasma propranolol concentrations of 3 to 30 ng/ml and a second at concentrations above 30 ng/ml. Only patients with increased sympathetic nervous system activity and high plasma renin activity (PRA) had substantial falls in pressure at propranolol levels of 3 to 30 ng/ml. Cardiac beta adrenergic receptor blockade, not suppression of PRA, seemed to be the antihypertensive mechanism. This relation of pretreatment sympathetic nervous activity and PRA to antihypertensive response existed only at lower plasma propranolol concentrations. With a propranolol dose of 320 mg daily, both plasma norepinephrine concentration and PRA were unrelated to the clinical response.     

Long Acting Propranolol in the Prophylaxis of Migraine. Comparison of the Daily Doses of 80 mg and 160 mg

SYNOPSIS
The efficacy of long acting propranolol in a dosage of 80 mg once daily in comparison to 160 mg once daily was assessed in the prophylactic treatment of migraine in a double-blind cross-over trial. 48 patients with classic or common migraine were included in the investigation, 6 patients withdrew, but only one because of side-effects. A four week run-in placebo period preceded the drug treatments, the duration of drug treatments was 12 weeks and there was a wash-out placebo period of 4 weeks between the treatments.
The two long acting propranolol doses, 80 mg and 160 mg once daily seemed to be equally effective. There was no difference in the antimigraineous effect. Long acting propranolol decreased both the frequency and severity of migraine attacks. Side-effects reported during the trial were mild, both doses were well tolerated. The treatment compliance during the once daily treatment was very good.     

The effect of the combination of quinidine and propranolol upon atrial and ventricular automatically in dogs.

The effects of quinidine, propranolol and their combination on atrial and ventricular automaticity were studied in pentobarbital-anesthetized dogs with complete heart block produced by injection of 40% formalin. The indices of atrial and ventricular automaticity were the intrinsic rate and the asystole interval, 10-beat period, and beats per 30 seconds after cessation of a 2-minute overdrive. Potentiation was considered to be a response produced by the combination of a half-dose of quinidine plus a half-dose of propranolol significantly greater than that produced by the full dose of either drug. Two combinations were studied: combination I consisted of 1.0 mg/kg of quinidine and 0.04 mg/kg of propranolol while combination II consisted of 2.0 mg/kg of quinidine and 0.08 mg/kg of propranolol. Neither combination potentiated the action of the individual drugs on the ventricle. Both combinations produced a potentiation of the individual drug effects on atrial intrinsic rate, asystole interval, and 10-beat period while only combination II potentiated the individual drug effects on atrial beats per 30 seconds. These studies indicate that the enhanced effect of the quinidine-propranolol combination in conversion of atrial tachyarrhythmias to sinus rhythm may be a function of its potentiation of the ability of the individual drug to depress atrial automaticity.     

Ultra-short-acting beta-blockade: a comparison with conventional beta-blockade

Esmolol is a beta 1-selective adrenoceptor blocker that is rapidly metabolized by blood and liver esterases. The beta-receptor and hemodynamic effects of esmolol were determined in a group of 12 healthy men and were compared with those induced by both oral and intravenous propranolol. Esmolol was rapidly effective in inducing at least 90% of steady-state beta-blockade within 5 minutes of either initiating or changing the esmolol infusion rate. More importantly, when esmolol infusion was discontinued the beta-blockade had totally disappeared by 18 minutes after esmolol, 300 micrograms/kg/min, and had been reduced by 50% after 750 micrograms/kg/min. In contrast, 30 minutes after discontinuation of a propranolol infusion, there was no change in the level of beta-blockade. Propranolol was much more potent at blocking isoproterenol-induced tachycardia (dose ratio 33.5 +/- 2.5) than was even the highest dose (750 micrograms/kg/min) of esmolol (dose ratio 13.1 +/- 1.0). The same dose of intravenous propranolol was approximately equipotent to oral propranolol, 40 mg every 8 hours (dose ratio 33.5 +/- 2.5 and 34.5 +/- 3.6, respectively). In contrast, propranolol, 40 mg every 8 hours, and esmolol, 300 micrograms/kg/min, were equipotent in antagonizing exercise-induced tachycardia (40.1% +/- 2.3% and 42.7% +/- 3.2%, respectively). Esmolol had striking hypotensive effects. Systolic blood pressure fell by 20 mm Hg during esmolol infusions of 750 micrograms/kg/min. Esmolol appears to be a potent beta 1-selective adrenoceptor antagonist with a particularly strong hypotensive effect. It is likely to be very useful in the treatment of hemodynamically unstable patients and may be useful in the emergency treatment of hypertension.     

Effect of Propranolol on Ventricular Rate During Atrial Fibrillation in the Wolff-Parkinson-White Syndrome

Atrial fibrillation was induced during an electrophysiology study in 10 patients with the Wolff-Parkinson-White (WPW) syndrome, after determination of baseline properties of the accessory atrioventricular (AV) connection; intravenous propranolol (0.2 mg/kg) was then administered. Atrial fibrillation terminated during the drug infusion in three patients, allowing determination of propranolol's effects on conduction and refractoriness during sinus rhythm, before atrial fibrillation was reinduced. In these three patients propranolol had no effect on refractoriness or conduction properties of the accessory AV connection during sinus rhythm. The mean ventricular rate during atrial fibrillation was slowed by 15–56 beats/min in six patients, had no effect on the mean rate in three patients, and markedly increased the ventricular rate (203 to 267 beats/min) in one patient. In this patient, 54% of QRS complexes during atrial fibrillation were narrow, compared to 0–25% in the other patients. Propranolol reduced the percentage of QRS complexes that were narrow from 13 ± 16% to 1 ± 2% (mean ± standard deviation, p < 0.05). We conclude that propranolol may slow the ventricular rate during atrial fibrillation in some patients with the WPW syndrome, probably by blockcing the effects of adrenergic activation. However, propranolol should not be used in patients with the WPW syndrome who have atrial fibrillation, if most QRS complexes during atrial fibrillation are preexcited. When a large percentage of QHS complexes are narrow, propranolol may increase the ventricular rate, probably by eliminating concealed retrograde conduction in the accessory AV connection.     

Propranolol treatment of effort angina in patients with arterial hypotension

AIM: To compare antianginal efficacy and tolerability of propranolol therapy in patients with stable angina pectoris and chronic hypotension (Hpts) and normotensive patients with angina of effort (Npts). MATERIAL AND METHODS: A randomized, single-blind, placebo-controlled study was made in 35 Hpts and 38 Npts was made using bicycle exercise tests, echocardiography, stress myocardial scintigraphy with 77-199. RESULTS: Acute bicycle exercise tests showed high anti-ischemic activity of propranolol in 86% Hpts and 65% Npts. Stable antianginal propranolol effect in 57% Hpts was accompanied with a decrease of myocardial perfusion defect. Secondary resistance or pseudotolerance to an antianginal effect of propranolol was observed in 43% Hpts in 4-12 weeks (vs 0 of Npts; p < 0.01) as evidenced by T-199 stress myocardial scintigraphy. Hpts with secondary resistance and pseudotolerance to propranolol had lower control hypotension and bradicardia (p < 0.05), more anginal attacks (p < 0.001). CONCLUSION: Hpts had rapidly developing secondary resistance and pseudotolerance to propranolol antianginal effect, bad tolerability of the drug.     

Renal haemodynamics during propranolol treatment in patients with arterial hypertension and chronic renal failure

The effect of propranolol on renal haemodynamics was studied in nine patients with arterial hypertension and moderate to severe chronic renal failure. A reduction of the renal function in this type of patient might have clinical consequence. The patients, whose glomerular filtration rate (GFR) ranged between 17 ml/min/1.73 m2 and 71 ml/min/1.73 m2, were studied during three 4-week periods with alternately placebo, propranolol (40 mg b.i.d.) and placebo treatment. The GFR and the effective renal plasma flow (ERPF) were determined as the plasma clearance of 51Cr-EDTA and 125I-hippurane. The GFR fell on the average 7% (95% confidence limits: 1-12%) during propranolol treatment, and the fall was reversible. No changes were found in ERPF. In conclusion, propranolol treatment in this type of patient causes a modest and reversible fall of GFR.