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PubMed1990

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.

Action Potentials↗
PubMed1977

The influence of propranolol on the thyrotropin receptor.

Propranolol, a beta adrenergic blocking drug, is known to inhibit the thyrotropin (TSH) stimulation of adenosine-3',5'-monophosphate (cyclic AMP production in thyroid membranes but the mechansim of this inhibitory action is known. We have therefore investigated the influence of propranolol on the binding of 125I-labelled TSH to human thyroid membranes. Both d- and l-propranolol were found to enhance the binding of 125I-labelled TSH to thyroid membranes. The amount of label bound increased from about 30% in the absence of propranolol to about 60% in the presence of 3.3 x 10(-3)M propranolol. Scatchard analysis of the binding data indicated that propranolol increased the association constant of the thyrotropin-thyrotropin receptor interaction. Practolol, lithium carbonate, methimazole, and somatostatin had no effect on thyrotropin binding. This effect of propranolol appeared to be due to a direct reversible action of propranolol on the thyroid membranes and could be attributed to the membrane-disrupting properties of the drug rather than its beta-blocking activity. The increased TSH receptor occupancy which resulted from the increased association constant of the TSH-thyroid membrane interaction corresponded with a decrease in TSH-stimulated cyclic AMP formation. These data could indicate that propranolol reduced the efficiency of the receptor-adenylyl cyclase coupling system.

Cell Membrane↗
PubMed1980

Inhibition by propranolol of 3,5,3'-triiodothyronine formation from thyroxine in isolated rat renal tubules: an effect independent of beta-adrenergic blockade.

Recent studies in man have shown a decrease in serum L-T3 (T3) levels in subjects treated with DL-propranolol, but the mechanism of this effect is unknown. Isolated rat renal tubules were used to study the effect of propranolol and related drugs on the formation of T3 from L-T4 (T4). Racemic (DL) propranolol at 100 microM inhibited the net formation of T3 from T4 by 35% (P less than 0.01). The D- and L-isomers of propranolol were also potent in inhibiting T3 formation, but the beta-blockers atenolol and sotalol, which have no significant membrane-stabilizing activity, had no effect at similar concentrations. Quinidine inhibited T3 formation, with a dose-response curve which was similar over the concentrations studied to that of DL-propranolol. L-Epinephrine and L-isoproterenol had no effect on T3 formation, and equimolar amounts of L-isoproterenol did not prevent the inhibition of T3 formation by DL-propranolol. cAMP production was stimulated by 200 micro M L-isoproterenol, and this was blocked by an equimolar concentration of DL-propranolol but not of D-propranolol. It is concluded that DL-propranolol directly inhibits net T3 formation from T4 in this system by a direct membrane-stabilizing or quinidine-like action and not by specific beta-blockade.

Adrenergic beta-Antagonists↗
PubMed1984

The beta-adrenoceptor-blocking drug propranolol prevents secretion of immunoreactive beta-endorphin and alpha-melanocyte-stimulating hormone in response to certain stress stimuli.

Handled female Wistar rats were exposed to one of the following stress stimuli: restraint, electric foot shocks, passive avoidance situation, ether, or nembutal anesthesia followed by ip formalin or laparotomy. Trunk blood was collected 2-4 min after initiation of the stress stimulus for the determination of immunoreactive beta-endorphin (beta-ENDi), ACTH (ACTHi), and alpha-MSH (alpha-MSHi). All stressors evoked a rapid increase of circulating beta-ENDi to 0.75-2.10 ng/ml. All except passive avoidance situation also induced a rapid increase of plasma ACTHi to 0.45-0.70 ng/ml, whereas plasma alpha-MSHi increased after ether and restraint to 0.18-0.40 ng/ml but was not affected by formalin stress. To study the involvement of a beta-adrenoceptor mechanism in stress-induced peptide secretion, rats were treated with D-propranolol or L-propranolol 40 min before stress exposure. Propranolol did not prevent the increase of plasma ACTHi to any of the stressors studied. L-Propranolol but not its inactive D-isomer reduced (restraint, passive avoidance) or abolished (electric foot shocks) the increase in plasma beta-ENDi but did not affect the beta-ENDi response to other stressors (ether, formalin, laparotomy). Similarly, L-propranolol attenuated the alpha-MSHi response to restraint but not to ether stress. To discriminate between corticotroph or melanotroph origin of beta-ENDi released during stress, rats were treated with dexamethasone or were subjected to neurointermediate lobectomy (4 weeks). Neurointermediate lobectomy did not affect basal or stress-induced plasma ACTHi but resulted in undetectable alpha-MSHi levels. It largely prevented the beta-ENDi response to restraint stress (propranolol sensitive) but had little effect on the beta-ENDi response to formalin stress (propranolol insensitive). Conversely, dexamethasone prevented stress-induced ACTHi response without affecting plasma alpha-MSHi. The beta-ENDi response to restraint stress (propranolol sensitive) was not changed but the response to formalin stress (propranolol insensitive) was largely prevented by dexamethasone. These results show that the intermediate lobe is the main source of beta-ENDi secreted during exposure to stressors with a high emotional impact. Since intermediate lobe peptide secretion induced by such stimuli can be prevented by beta-adrenoceptor blockade, we speculate that stress-induced discharge of catecholamines, possibly from the adrenal medulla, is the trigger signal for peptide secretion from the melanotrophs during this type of stress.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Propranolol and cardiac surgery: a problem for the anesthesiologist?

Propranolol therapy has been implicated as a cause of myocardial depression and increased morbidity and mortality in patients undergoing coronary artery surgery. The authors reviewed 169 consecutive patients undergoing cardiac surgery, of whom 143 had been taking propranolol, with regard to preoperative administration of propranolol and intraoperative or postoperative complications. Patients taking propranolol until 24 hours before surgery showed no increased incidence of hypotension or bradycardia before cardiopulmonary bypass. Hypotension after bypass was no more common in patients off propranolol 12 to 48 hours than in patients who either discontinued the drug over 48 hours before operation or had never taken the drug. Myocardial contractility as measured by systolic time intervals was normal 24 to 48 hours after stopping propranolol therapy. Five patients had preoperative myocardial infarctions within 48 hours of discontinuing the drug. The operative mortality rate was 4 percent in patients taking propranolol within 48 hours of surgery and 6 percent in all other patients. Seven risk factors, other than propranolol, were identified in those patients requiring inotropic support. The authors conclude that propranolol can be given safely within 24 to 48 hours of coronary artery surgery provided the patient is a satisfactory candidate for myocardial revascularization.

Angina Pectoris↗
PubMed1992

Accumulation of propranolol in cultured rat fibroblasts.

In order to clarify the involvement of phosphatidylserine (PhS) in the cellular accumulation of propranolol, we have characterized the binding of 3H-propranolol to cultured rat fibroblasts and to liposomes containing PhS. The properties of propranolol binding to the cells and liposomes were analyzed by means of a Scatchard plot. The cells contained at least two classes of propranolol binding sites, one site of high affinity/low capacity and the second site of lower affinity/higher capacity, while the liposomes contained only one class of binding site. The values of the association constant (K) and number of binding sites (n), given on a PhS basis for the propranolol binding site in the liposomes, were both very close to those of corresponding binding parameters for the high affinity/low capacity binding site in the cells. Cell death, caused by various toxic reagents, resulted in a marked decrease in propranolol accumulation in the cells. Kinetic analysis of the drug binding to dead cells showed one binding site with binding parameters comparable to those of the low affinity/high capacity binding site in the intact cells. Polar cations, methylamine and NH4Cl, completely inhibited propranolol binding to the liposomes. On the other hand, these cations partially inhibited propranolol accumulation in intact cells and failed to inhibit the drug binding to dead cells. These results suggest that PhS in cytomembranes represents the high affinity/low capacity propranolol binding site in cultured rat fibroblasts.

Ammonium Chloride↗
PubMed1984

Increased availability of propranolol in rats with uranyl nitrate-induced acute renal failure.

The effect of acute renal failure (ARF) on the pharmacokinetics of propranolol was investigated. The model of ARF was produced by the subcutaneous injection of uranyl nitrate to rats (10 mg/kg) and was used 3 d after treatment. Uranyl nitrate-treated rats showed significantly higher plasma concentrations of propranolol after oral administration and the area under the plasma concentration-time curve increased about 3-fold compared to control rats. The plasma disappearance of propranolol after intravenous administration did not differ significantly between control and ARF. The mean availability of propranolol after oral administration increased from 0.120 in control to 0.215 in ARF (p less than 0.005). Absorption of propranolol was almost complete and no significant difference was found between two groups. No changes in plasma protein binding of propranolol and hepatic blood flow were observed in ARF. On the other hand, hepatic clearance of propranolol determined by liver perfusion studies showed a significant reduction in ARF and the calculated intrinsic clearance of unbound propranolol at a dose of 6.25 mg was 26.8 +/- 2.3 ml/min in control and 16.0 +/- 2.3 ml/min in ARF (p less than 0.01). These results demonstrate that the oral availability of propranolol increased in ARF due to a reduction in the hepatic presystemic elimination as compared to healthy control rats.

Acute Kidney Injury↗
PubMed2003

Propranolol cytotoxicity in rat and human lung in vitro.

Propranolol is a lipophilic nonselective beta blocker mainly eliminated via the liver. The specific architectural arrangement of the mammalian lung favors the filtration of so-called pneumophilic drugs out of the blood and retention within the tissue, as shown in particular for amphetamine, amiodarone, imipramine, chlorpromazine, propranolol and local anesthetics. In the current study we tested in vitro the susceptibility of freshly isolated rat type II pneumocytes (RTII), rat alveolar macrophages (RAM), human alveolar macrophages (HAM) and A549 human lung adenocarcinoma cell line (A549) to propranolol (0.001-1 mM). Cytotoxicity was evaluated by changes in membrane integrity (lactate dehydrogenase [LDH] assay) and mitochondrial metabolic activity (reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) after 3-h and 20-h incubation with propranolol. In all tested lung cells, propranolol caused concentration-dependent decreases of MTT reduction and LDH retention in the fraction of attached cells, which was associated with an increase of LDH activity in the medium and in the fraction of non-attached cells. After 3-h incubation, the reduction of MTT was significantly decreased compared with control at > or = 1 x 10(-4) M in HAM, at > or = 5 x 10(-4) M in A549 and significantly decreased of LDH retention in the fraction of attached cells in HAM and in A549 at > or = 5 x 10(-4) M. After 20-h incubation the reduction of MTT was significantly decreased compared with control at > or = 1 x 10(-6) M in RAM, at > or = 5 x 10(-5) M in RTII and HAM and > or = 5 x 10(-4) M in A549. Propranolol caused a significant decrease of LDH retention in the fraction of attached cells (> or = 5 x 10(-5) M, RAM and RTII; > or = 5 x 10(-4) M, HAM and A549). The cytotoxic effect of propranolol in HAM and A549 was more pronounced after prolongation of incubation time (from 3 h to 20 h). These results showed that rat and human lung cells were sensitive to propranolol concentration < or = 1 mM in vitro. We suppose that the damaging action of propranolol on the lungs might be mediated by physicochemical properties of moiety and its pulmonary metabolites.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Effect of propranolol on delayed glucose recovery after insulin-induced hypoglycemia in normal and diabetic subjects.

In order to evaluate the influence of beta-adrenergic blockade on recovery from insulin-induced hypoglycemia, we compared the effect of saline or propranolol infusion during concomitant hypoglycemia in normal and type I diabetic persons. The diabetic subjects were initially rendered euglycemic with a basal insulin infusion. Glucose turnover was measured using [3-3H]glucose tracer. Propranolol caused a small but significant delay in glucose recovery in normal subjects, with plasma glucose only 80% of the values seen during saline infusion 1 h after hypoglycemia (P less than 0.005). This delay was caused by a 70% reduction in the rebound glucose output, which was responsible for posthypoglycemic recovery. In the diabetic subjects, glucose recovery was significantly delayed as compared with that in normal persons, even in the absence of propranolol, and associated with reduced secretion of epinephrine and glucagon. Moreover, the addition of propranolol caused a further 50% reduction in glucose recovery such that plasma glucose remained below 50 mg/dl for 3 h. In contrast to normals, propranolol did not inhibit the already blunted rebound in glucose output. However, propranolol prevented the decline in glucose utilization that occurred when saline alone was infused. During saline infusion, glucose uptake was at basal rates by 60 min whereas, during propranolol administration, glucose uptake remained above baseline until 180 min (P less than 0.01). Thus, propranolol may interfere with glucose recovery after insulin-induced hypoglycemia in diabetic patients by blocking epinephrine's inhibition of glucose utilization whereas, in normals, propranolol's effect is largely accounted for by blockade of epinephrine-induced hepatic glucose production.

Blood Glucose↗
PubMed1991

Long-term effects of oral propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis and oesophageal varices.

Splanchnic and systemic haemodynamics were measured in 24 patients with cirrhosis and oesophageal varices and no previous bleeding. The patients were randomized either to long-term treatment with propranolol (14 patients) or no active treatment (controls, 10 patients). Catheterization was performed again 1 year after randomization. After 1 year of treatment the hepatic venous pressure gradient had decreased in both the propranolol and control group (-16% versus -24% (NS), respectively). Hepatic blood flow decreased substantially in both groups but significantly more in the propranolol group (-39% versus -17% (p less than 0.05), respectively). Azygos blood flow was significantly reduced after 1 year in the propranolol group (-47%, n = 5 (p less than 0.05)), and no obvious effect was observed in the control group (-2%, n = 4). The cardiac index decreased significantly in the propranolol group but not in the control group (-20% versus -1% (p less than 0.05), respectively). Our results demonstrate that the splanchnic hyperdynamic condition observed in cirrhosis is in some of the patients partly reversible without pharmacologic treatment. No additional effect of propranolol was observed on portal pressure after 1 year of treatment with propranolol, whereas a decrease in azygos blood flow was observed only in the propranolol group. The beneficial effect of propranolol on the risk of bleeding from oesophageal varices may, therefore, mostly be due to a selective decrease in collateral blood flow and thereby variceal blood flow.

Administration, Oral↗
PubMedDate not supplied

Use of fluorescent probes to monitor propranolol effects on the murine splenic lymphocyte.

Recent studies indicate that propranolol suppresses the normal murine lymphocyte mitogen dose-response(1) and that propranolol has a high affinity for the beta-adrenergic binding site on the murine lymphocyte(2). Since concentrations which suppress the lymphocyte mitogen dose-response are much greater than the Kd for the binding site, it may be suggested that the suppression of the mitogen dose-response is a result of nonspecific effects of propranolol. Three fluorescent probes (1,6-diphenyl-1,3,5-hexatriene (DPH), fluorescein conjugated concanavalin A (F-Con A), and 3,3'-dithio-diisopropyl-oxacarbocyanine iodide (diS-C3-(5)) were used to investigate possible mechanisms of the nonspecific effects of propranolol on the murine splenic lymphocyte. This report presents data which suggests a possible relationship between propranolol concentrations that alter lipid membrane dynamics, as monitored by the fluorescence polarization of DPH, and suppression of the mitogen dose-response in short term cell cultures as effected by propranolol. Also reported are effects of propranolol on the relative mobility of surface membrane lectin receptors as monitored by the fluorescence polarization of F-Con A, effects of propranolol on the transmembrane potential as monitored by fluorescence emission of diS-C3-(5), and the propranolol effect on fluorescence polarization temperature-dependence of DPH and F-Con A. Studies of the effects of sotalol, alprenolol, and metoprolol are included and used for the comparison of different drug effects.

Alprenolol↗
PubMed2005

Propranolol increases the complexity of heart rate fluctuations--a mode of antiarrhythmic action?

OBJECTIVE: To study the beta-blocking effect of propranolol on heart rate and arterial blood pressure fluctuations in healthy subjects using linear methods and a set of nonlinear models. METHODS: In a randomized, double-blind, placebo-controlled study, healthy young adults received a 40 mg oral dose of propranolol (n = 12) or placebo (n = 12). The effects of propranolol and placebo were assessed using time series of the RR interval (RRI) and systolic arterial blood pressure (SAP) obtained from continuous ECG and blood pressure signal recordings. Heart rate and systolic arterial blood pressure fluctuations were analyzed using nonlinear and linear methods of time series statistics. RESULTS: Propranolol significantly increased the complexity of heart rate fluctuations in terms of symbol dynamic (SymDyn) entropy and symbol dynamic percentage of forbidden words. Propranolol augmented cross entropy between RRI and SAP and increased fractal dimension of RRI. beta-blockade also affected linear measures of RRI fluctuations by increasing parasympathetic, respiration-related high-frequency (HF) variability and arterial baroreflex-related low-frequency (LF) variability. Propranolol administration, however, had no effect on the complexity of SAP fluctuations assessed using nonlinear time series statistics. CONCLUSIONS: beta-blockade by propranolol has a differential effect on RRI and SAP fluctuations in healthy subjects. Propranolol increases the complexity of RRI fluctuations. The effect is associated with the cardiac vagotonic drug action of propranolol. SAP fluctuations are almost unchanged. The increased complexity of RRI fluctuations may be a beneficial feature of beta-blockade, since many cardiovascular diseases decrease the complexity of RRI time series by dampening cardiovascular reflex actions.

Administration, Oral↗
PubMed2003

Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.

BACKGROUND: For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the beta-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. METHODS: Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. RESULTS: Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. CONCLUSIONS: Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the beta-blockade effect of propranolol in Chinese subjects.

Aryl Hydrocarbon Hydroxylases↗
PubMed1992

Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study.

Nicorandil is a potent coronary vasodilator. To assess its long-term antianginal effect, we designed a randomized, parallel double-blind trial of 6 weeks' duration comparing nicorandil (10 or 20 mg b.i.d.) with propranolol (40 or 80 mg t.i.d.). The study comprised 77 men with stable angina, no maintenance medication at entry, and an exercise test positive for angina and ST-segment depression. The therapy was started with 10 mg nicorandil b.i.d. or 40 mg propranolol t.i.d. After 3 weeks, the dosage could be doubled according to clinical criteria. Four men receiving nicorandil and one receiving propranolol were withdrawn with side effects; in three cases, the data were not complete. Thus, comparative data were obtained in 69 patients; in 51 of these (26 receiving nicorandil and 25 receiving propranolol), the dosage was increased to the higher level. Blood pressure and heart rate were unaltered by nicorandil and lowered by propranolol. The number of anginal attacks decreased relative to baseline on nicorandil and propranolol (p < 0.002), but total exercise duration was not influenced by either drug. The exercise test performed 2 h after either pill ingestion showed a decrease and a delay in occurrence of myocardial ischemia. The test performed 12 h after medication exhibited reduced ischemia, whereas only propranolol resulted in delayed ST-segment depression. The double product of heart rate and systolic blood pressure was affected only slightly by nicorandil and reduced significantly by propranolol (p < 0.001). Thus, nicorandil medication affords similar improvement as propranolol in patients with angina pectoris, but the mode of action appears to be different.

Angina Pectoris↗
PubMed1992

Pulmonary accumulation of propranolol in vivo: sites and physiochemical mechanism.

Despite the therapeutic importance of propranolol and the potential usefulness of propranolol extraction measurements for the assessment of lung disorders, the pulmonary disposition of propranolol remains poorly understood. The extraction, accumulation and distribution of propranolol in lungs of conscious and anesthetized sheep were investigated by indicator-dilution methods, lung lymph fistula preparations and bronchoalveolar lavage. Pulmonary extraction of propranolol from plasma (0.81 +/- 0.03) was significantly less than that of imipramine (0.89 +/- 0.03), not significantly different from that of lidocaine (0.74 +/- 0.03) and much greater than that of water (0.44 +/- 0.02), whereas there were no differences in apparent red blood cell extraction of each indicator from plasma in vitro as determined under similar conditions (0.08-0.1). Pulmonary accumulation of imipramine (78 +/- 3%), lidocaine (52 +/- 4%), propranolol (37 +/- 4%) and water (7 +/- 2%), after a single pass through the pulmonary circulation, correlated positively with octanol/saline partition coefficients but not with pKa values. After bolus i.v. injection of [3H]propranolol, tritium concentrations in lung lymph increased rapidly to exceed plasma concentrations within 60 min and tritium concentrations in bronchoalveolar lavage equaled plasma concentrations 5 to 15 min after injection. It is concluded that by a mechanism not involving molecular charge, propranolol permeates capillary endothelium and alveolar epithelium to accumulate in hydrophobic regions of the lungs. This study in normal sheep suggests that reduced propranolol extraction by damaged lungs reflects pathological alterations other than endothelial cell dysfunction, such as pulmonary edema.

Animals↗
PubMed2003

Value of propranolol-induced heart rate and blood pressure changes in predicting results of tilt testing.

BACKGROUND: A degree of reduction of heart rate (HR) and blood pressure (BP) values following beta-blocker administration has been shown to indicate beta-blockade effectiveness. Whether this parameter is also useful in the identification of patients with vaso-vagal syncope (VVS) who could benefit from beta-blocker therapy, has not yet been established. AIM: To analyse the usefulness of propranolol-induced acute changes in HR and BP in the prediction of the results of tilt testing (TT) in patients with VVS. METHODS: The study group consisted of 37 patients with a history of at least two syncopal episodes in the past 6 months, in whom syncope was reproduced during TT. After positive baseline TT the patients were returned to supine position and were given intravenous propranolol. After 15 min supine rest the patients were tilted again using the same protocol as during the baseline test. Propranolol was considered effective when the result of the second (on drug) TT was negative or the time to syncope occurrence was longer than during baseline TT. During the whole procedure systolic BP (SBP), mean BP (MBP), diastolic BP (DBP) and HR were measured. These parameters were analysed in four different time-intervals: period I - between 13th and 15th minute of supine rest preceding the passive phase of TT, period II - between first and third minute of the passive TT, period III - following propranolol injection, between 13th and 15th minute of supine rest preceding second TT, and period IV - between first and third minute of second TT, either passive (if positive) or after NTG administration. Both, mean values and differences (Delta) in analysed parameters between various time-intervals (II-I, III-I, IV-II and IV-III) were taken into account. RESULTS: Intravenous propranolol occurred effective in preventing syncope during second TT in 29/37 (78%) patients. The DeltaSBP, DeltaMBP and DeltaDBP values calculated from periods III and IV were significantly different between patients with or without protective effects of propranolol. The cut-off values which were computed to obtain the highest value of total predictive accuracy (the highest value of the sum of sensitivity and specificity) were -5 mmHg for DeltaSBP, -4 mmHg for DeltaMBP and -2 mmHg for DeltaDBP. A stepwise logistic regression analysis revealed that DeltaSBP of -5 mmHg or less had the highest value in the prediction of a positive response to propranolol, reaching a sensitivity of 72%, specificity of 88%, positive predictive value of 95% and negative predictive value of 48%. CONCLUSIONS: Propranolol-induced changes in blood pressure values may predict the effectiveness of beta-blockade in preventing syncope during second TT performed after intravenous infusion of propranolol. A drug-induced reduction in systolic blood pressure of less than 5 mmHg may identify those who will benefit from beta-blocker therapy.

Adrenergic beta-Antagonists↗
PubMed1977

Association of in vivo and in vitro propranolol levels in canine Purkinje fibers with antiarrhythmic effects.

This study has determined the propranolol content of Purkinje fibers associated with antiarrhythmic and electrophysiological actions of the drug both in vivo and in vitro. The minimum effective tissue content of propranolol that consistently reversed a sustained ouabain-induced ventrivular tachycardia in vivo after i.v. propranolol was between 6.7 and 11.1 micron g/g of tissue. Propranolol doses producing Purkinje fiber contents of less than 6.7 micron g/g failed to revert the arrhythmia but did ponotropic responses to 0.5 micron g/kg of isoproterenol. The in vivo minimum effective tissue content was produced in isolated Purkinje fibers perfused with Tyrode's solution containing 1.7 X 10(-6) M propranolol. In Purkinje fibers this concentration of propranolol depressed the rate of phase 4 depolarization previously enhanced by ouabain 2.1 X 10(-7) M. Propranolol, 1.7 X 10(-6) M, did not alter membrane responsiveness and only slightly accelerated repolarization at 5 minutes. Propranolol, 0.85 X 10(-6) M, did not significantly depress the ouabain-enhanced rate of phase 4 depolarization but did attenuate the response to epinephrine through beta blockade. This study indicated that the initial direct action of propranolol in reverting a ouabain-induced ventricular tachycardia to a sinus rhythm in the dog is depression of automaticity.

Action Potentials↗
PubMed1991

[Oral propranolol in Wolff-Parkinson-White syndrome. Electrophysiological data].

The effects of oral propranolol were studied in 24 patients with the WPW syndrome. The average daily dose of propranolol was 130 +/- 24 mg administered in 3 doses over a period of 48 to 72 hours. Endocavitary electrophysiological study was performed 2 to 4 hours after the last dose. The effective anterograde refractory periods (EARP) of the accessory and normal pathways were measured before and after propranolol (and, in both studies, before and after isoproterenol). The EARP of the accessory pathway was not affected by the propranolol. However, in the 9 patients in whom its value was less than 270 ms, it increased significantly (p = 0.01). The EARP of the accessory pathway measured after administration of isoproterenol increased significantly in all patients with oral propranolol (p = 0.001). Sustained reciprocating tachycardia could be induced in 19 patients and non-sustained reciprocating tachycardia in 5 other patients during base line electrophysiological study. Oral propranolol prevented the induction of the tachycardias in 18 patients (75%), even after isoproterenol. The shortest R-R interval between two pre-excited complexes in atrial fibrillation increased after propranolol (283 +/- 45 to 343 +/- 95 ms). These results show that oral propranolol increases the EARP of the accessory pathway and the shortest R-R interval between two pre-excited complexes in atrial fibrillation in patients with short anterograde refractory periods of their accessory pathways, and is effective in preventing reciprocating tachycardia. Oral propranolol may be useful and can be used safely in patients with the Wolff-Parkinson-White syndrome.

Administration, Oral↗