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PubMed1992

Fluorescence studies of beta-adrenergic ligand binding to alpha 1-acid glycoprotein with 1-anilino-8-naphthalene sulfonate, isoprenaline, adrenaline and propranolol.

The present study shows that ANS (1-anilino-8-naphthalene sulfonate), propranolol, isoprenaline, adrenaline and dopamine have common binding sites on AAG (alpha 1-acid glycoprotein). A fluorescence technique was employed to characterize the interaction between the ligands and AAG at 20-22 degrees. The binding of ANS to AAG caused increased fluorescence intensity at emission and excitation wavelengths of 400 and 470 nm. In this situation, propranolol displaced ANS in a concentration-dependent mode with an apparent dissociation constant of 6.2 +/- 0.01 microM, whereas isoprenaline did not reduce the ANS-AAG fluorescence. However, in the presence of AAG, catecholamines caused a marked increase of fluorescence at excitation and emission wavelengths of 250 and 325 nm, respectively. These wavelengths were employed to characterize the binding of isoprenaline, adrenaline and propranolol to AAG. Two subsets of binding sites were demonstrated. The Kd values were 0.87 +/- 0.03 and 25.1 +/- 10.7 microM for ANS, 0.76 +/- 0.09 and 133 +/- 30.4 microM for propranolol, 140 +/- 14 and 2.18 +/- 0.58 mM for isoprenaline, 137 +/- 24 and 14.8 +/- 0.1 mM for adrenaline, respectively. AAG had identical high affinity binding capacity for these ligands (n approximately 1). However, the second class of binding sites showed ligand-dependent binding capacity: n = 1 for ANS, n approximately 10 for propranolol, n approximately 15 for adrenaline, n approximately 20 for isoprenaline, respectively. ANS, propranolol, dopamine and adrenaline caused concentration-dependent inhibition of isoprenaline binding to AAG with apparent dissociation constants of 5.1 +/- 1.8 microM, 6.4 +/- 1.1 microM, 0.57 +/- 0.13 mM and 1.5 +/- 0.46 mM, respectively.

Anilino Naphthalenesulfonates↗
PubMed1993

The effect of hypoxia on propranolol clearance during antegrade and retrograde flow in the isolated perfused rat liver preparation.

We investigated, using the single-pass isolated perfused rat liver preparation, whether the centrilobular location of hepatic oxidative drug metabolism could be a contributing factor to the marked sensitivity of drug oxidation to hypoxia. Livers (N = 7) were each perfused for 130 min with 2 micrograms/mL (+)-propranolol, a drug metabolized almost entirely by oxidation in the rat. The direction of flow was reversed after 60 min, the order of flow direction being randomized. Normal oxygenation was used during the first 30 min of antegrade and of retrograde perfusion, but in the second 30 min perfusate was equilibrated with a N2/O2 mixture designed to reduce hepatic oxygen delivery by half. During normal oxygenation there was no significant difference between antegrade and retrograde perfusion in hepatic oxygen delivery and physiological parameters such as oxygen consumption and extraction, perfusion pressure and bile flow. During hypoxia, mean oxygen delivery was slightly lower with retrograde perfusion (retrograde: mean = 2.37 mumol/min/g liver, range = 1.56-3.17; antegrade: mean = 2.90 mumol/min/g liver, range = 1.96-4.08; P = 0.04), but there was no significant difference in physiological parameters within each liver (P > 0.05). Propranolol clearance during normal oxygenation was similar to the perfusion rate (10 mL/min) and was the same for both directions of perfusion (antegrade 9.88 +/- 0.07 mL/min, retrograde 9.88 +/- 0.13 mL/min, P > 0.05). Hypoxia reduced propranolol clearance substantially, but the decrease was significantly greater with antegrade perfusion (5.65 +/- 1.89 mL/min) than with retrograde perfusion (6.76 +/- 1.95 mL/min, P = 0.014). Oxidative drug metabolism is located primarily in the centrilobular zone and sinusoidal oxygen concentration is lowest in the "downstream" zone with both antegrade and retrograde perfusion. These findings suggest that the centrilobular location of propranolol metabolism may influence the effect of hypoxia on propranolol elimination, but is not a major contributor to the marked sensitivity of propranolol elimination to hypoxia antegrade perfusion.

Animals↗
PubMed1996

Membrane stabilizing, anti-oxidative interactions of propranolol and dexpropranolol with neutrophils.

We have investigated the effects of the beta-adrenoreceptor-blocking agent, propranolol (9-300 microM) on several pro-inflammatory activities of human neutrophils in vitro. Superoxide production by calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (9-18.7 microM) of this drug. However, inhibition of superoxide generation by neutrophils activated with phorbol myristate acetate (PMA), opsonized zymosan (OZ), and arachidonate (AA) only occurred with higher concentrations of propranolol, and coincided with decreased intracellular calcium fluxes, phospholipase A2 (PLA2) activity and synthesis of platelet-activating factor (PAF). Propranolol possessed neither cytotoxic nor superoxide-scavenging properties but, using a haemolytic assay of membrane-stabilizing activity, this agent neutralized the membrane-disruptive effects of the bioactive phospholipids, lysophosphatidylcholine (LPC), PAF, and lysoPAF(LPAF). A mechanistic relationship between the anti-oxidative and membrane-stabilizing properties of propranolol was suggested by the observation that pretreatment of neutrophils with LPC or PAF eliminated the inhibitory effects of the drug on superoxide generation by PMA-activated neutrophils. Dexpropranolol, a stereoisomer with minimal beta-blocking activity, and propranolol were equally effective with respect to their membrane-stabilizing and anti-oxidative interactions with neutrophils, but several other beta-blocking agents (atenolol, metoprolol, sotalol, and timolol) did not possess these activities. Inhibition of oxidant generation is, therefore, not a common property of beta-blocking agents and, in the case of propranolol, appears to occur as a consequence of membrane-stabilization rather than by beta-receptor-directed effects.

Acridines↗
PubMed1995

Stereoselective increase of plasma concentrations of the enantiomers of propranolol and atenolol during exercise.

OBJECTIVE: In vitro studies have shown that, like catecholamines, both propranolol and atenolol are taken up by and released from adrenergic cells. We performed this study to investigate whether this may also play a role in humans and whether stereoselective aspects are important. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study of two groups of 12 healthy volunteers. Subjects received single oral doses of 80 mg (R,S)-, 40 mg (R)-, and 40 mg (S)-propranolol; 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol; and placebo at intervals of 1 week. Exercise was performed at 4 and 9 hours after drug intake, and blood samples were taken before and at the end of each exercise period. The plasma concentrations of the (R)- and (S)-enantiomers of propranolol and atenolol, as well as those of epinephrine and norepinephrine, were determined by HPLC. RESULTS: Effects of exercise on the plasma levels of the enantiomers of propranolol and atenolol were similar. When the optically pure enantiomers were administered, exercise caused a marked and significant increase of the plasma concentrations of the (S)- but not of the (R)-enantiomers. When the drugs were administered in the racemic form, the plasma levels of both the (R)- and (S)-enantiomers were elevated to the same extent. The increase of norepinephrine levels during exercise was more pronounced than that of epinephrine and paralleled that of the (S)-enantiomers of the beta-blockers. CONCLUSION: Bearing the in vitro data in mind, we conclude that (S)-propranolol and (S)-atenolol are taken up into and released from adrenergic cells together with norepinephrine during exercise. The reason why the plasma concentrations of (R)-propranolol and (R)-atenolol are increased only during exercise in the presence of the corresponding (S)-enantiomers remains to be determined.

Administration, Oral↗
PubMedDate not supplied

Antagonism by propranolol of the ganglion stimulant action of 5-hydroxytryptamine.

The effects of racemic propranolol and its constituent isomers were studied on ganglionic stimulation produced in situ by close arterial injection of 5-HT and DMPP to the superior cervical ganglion. Ganglion stimulation was recorded in terms of the resultant contraction of the nictitating membrane. d,l-Propranolol caused a biphasic antagonism of the ganglion stimulant effect of 5-HT. At low doses, 0.5-10 mug, the antagonism was surmountable by increasing the amount of 5-HT. The l-isomer (0.2-4 mug) but not d-propranolol also caused antagonism. At higher doses, 0.1-5 mg, both d,l- and d-propranolol caused a second type of blockade of 5-HT which was not surmountable and resembled that seen with procaine. The ganglion stimulant effects of DMPP and acetylcholine were only antagonised by the higher doses of d- and d,l-propranolol. d,l-Propranolol did not reduce the direct stimulation by 5-HT on the muscle of the nictitating membrane.

Acetylcholine↗
PubMed1987

Effects of intracoronary propranolol on coronary blood flow and regional myocardial function in dogs.

The study was conducted to evaluate the effects of intracoronary administration of dl-propranolol on coronary blood flow and regional myocardial function in anesthetized open-chest dogs. The results were compared with those obtained with d-propranolol, atenolol and lidocaine. Bolus intracoronary injections of dl-propranolol (0.02-2 mg) dose dependently produced transient increases in coronary blood flow and subsequent depression in regional segment shortening which qualitatively resembled those produced by the dextro isomer (0.02-2 mg) and lidocaine (0.2-10 mg). Atenolol (up to 2 mg) was almost devoid of these effects. Isoproterenol-induced responses were abolished by dl-propranolol and atenolol but only incompletely blocked by d-propranolol. These results demonstrate that propranolol at high doses has direct coronary vasodilating and cardiodepressant effects in situ, and indicate that the major part of these effects can be attributed to the membrane-stabilizing action rather than beta-adrenoceptor blockade.

Animals↗
PubMed1990

Propranolol in the prevention of recurrent variceal hemorrhage in cirrhotic patients. A controlled trial.

A double-blind controlled study of long-acting propranolol in the secondary prevention of variceal hemorrhage was conducted in 81 cirrhotic patients. After the index hemorrhage, all patients were treated with injection sclerotherapy on one occasion to secure hemostasis and then randomized within 72 h to propranolol or placebo therapy which was continued for 2 yr. Study endpoints were severe recurrence of variceal hemorrhage or death. Forty-two patients did not fulfill the entry criteria for the study. Thirty-eight patients received propranolol of whom 18 (47%) had further hemorrhage, 14 died, eight had side-effects (2 withdrawals), and 3 did not complete follow-up. Forty-three patients received placebo of whom 33 (77%) had further hemorrhage, 19 died, 5 had side-effects (2 withdrawals), and 5 failed to complete follow-up. The median time from onset of hemorrhage to starting drug therapy was 6 days for both groups. Life table analysis showed an equivalent incidence of further hemorrhage in both groups over the first 60 days, following which the propranolol group did consistently better than the placebo group. There was a significantly lower incidence of rebleeding in modified Child's C patients receiving propranolol (39%) than those on placebo (90%). No statistically significant effect on mortality was seen. In this study, propranolol reduced the incidence of late recurrence of variceal hemorrhage in patients with cirrhosis.

Double-Blind Method↗
PubMed1992

Effect on hemodynamics of a liquid meal alone and in combination with propranolol in cirrhosis.

Thirteen patients with alcoholic cirrhosis had splanchnic and systemic hemodynamics assessed before and after ingestion of a standard liquid meal of 700 kcal (consisting of isocaloric proteins, lipids, and carbohydrates). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. No significant effects were observed on systemic hemodynamics after the meal alone. Heart rate (-14%; P less than 0.01) and cardiac index (-24%; P less than 0.01) decreased after meal in combination with propranolol. The mean hepatic venous pressure gradient increased significantly after ingestion of the meal alone with a maximal effect after 30 minutes (+13%; P less than 0.05) and returned to baseline values after 2 hours. Meal in combination with propranolol had no significant effect on the hepatic venous pressure gradient. Hepatic blood flow increased substantially after the meal alone with a maximal effect after 30 minutes (+28%; P less than 0.01), whereas no significant effect was observed after meal in combination with propranolol. Azygos blood flow increased significantly after the meal alone (+36%; P less than 0.05), whereas this effect was abolished in combination with propranolol. In conclusion, ingestion of a peroral mixed meal in cirrhotic patients has, contrary to what is observed in normal controls, no effects on systemic hemodynamics. Substantial changes in splanchnic hemodynamics were observed, and these effects were all abolished when the meal was administered in combination with propranolol.

Analysis of Variance↗
PubMed1988

Propranolol delays the formation of aneurysms in the male blotchy mouse.

Propranolol has been reported to prevent aortic aneurysms in the beta-aminoproprionitrile-fed broad-breasted white turkey model. The purpose of this investigation was to determine the effect of propranolol in another animal model of aortic aneurysms, the spontaneously aneurysm-prone Blotchy (BLO) mouse. One hundred fourteen male BLO mice were fed control chow or a diet supplemented with 0.10% (w/w) propranolol. Groups were sacrificed at monthly intervals and the presence of aneurysms was determined after latex injection into the left ventricle. Aortic diameter was also measured at the widest point in a subset of mice from each group sacrificed at 4-5 months of age. At 4 months 86% of control and 32% of propranolol-fed animals had aneurysms (P less than 0.001). The difference in mean aortic diameter was also decreased by 33% in the propranolol-fed group (P less than 0.01). This study suggests that propranolol delays the formation of aneurysms in this spontaneous, genetically determined animal model.

Animals↗
PubMed1994

Propranolol antagonizes coronary artery relaxation by a potassium channel opener.

Coronary artery preparations from cattle hearts responded with stable contractions to the thromboxane A2 analogue, U 46619. These contractions were progressively reduced by increasing concentrations of the prototypical potassium channel opener pinacidil (3.8 x 10(-8) to 1.1 x 10(-4) M). Pinacidil-induced relaxations were antagonized significantly by d,l-propranolol (1.2 x 10(-6) to 1.2 x 10(-5) M). Forskolin-induced relaxations of coronary preparations were also antagonized by d,l-propranolol, but those to nitroprusside were not. d-Propranolol also antagonized relaxations to pinacidil but only when used in higher concentrations than the I-isomer. Nadolol and metoprolol, two other beta receptor antagonists with differing profiles of action, also antagonized to some extent the vasodilator action of pinacidil. The known potassium channel antagonist, glibenclamide, shifted the concentration-relaxation curve for pinacidil to the right, but d,l-propranolol produced an additional antagonistic effect in the presence of glibenclamide. Relaxations of contracted tracheal ring preparations of guinea pig by pinacidil, however, were not antagonized by d,l-propranolol, suggesting specificity for vascular tissue. Isoproterenol increased significantly the cyclic AMP levels in coronary tissue, but pinacidil had no such effect, ruling out an adrenergic component to pinacidil action. Pinacidil increased the efflux of 86Rb in isolated coronary preparations, and this effect was blunted by propranolol. It is concluded that beta receptor antagonists inhibit relaxations to a potassium channel opener by a mechanism independent of beta adrenergic receptors and that this effect may have therapeutic implications.

Adrenergic beta-Agonists↗
PubMed1975

Metabolic effects of propranolol in thyrotoxicosis. I. Nitrogen, calcium, and hydroxyproline.

The effect of propranolol on the hypermetabolism of thyrotoxicosis was investigated in eight subjects with diffuse toxic goiter. After equilibration on a constant nitrogen, calcium, and hydroxproline intake, nitrogen balance was determined before and during propranolol therapy prior to subtotal thyroidectomy and compared to similar data obtained in seven of the patients following surgically induced euthyroidism. Propranolol administration was associated with clinical amelioration and a rapid, statistically significant, improvement in nitrogen retention. A slight additional improvement in retention was noted in the postoperative euthyroid state. Oxygen consumption, measured serially in four patients, was not significantly changed by propranolol. Urinary loss of calcium, phosphorus, and hydroxyproline was unaffected by propranolol, but excretion of these substances was sharply reduced in the subjects restudied postoperatively. These data offer a evidence of a previously unreported nitrogen sparing effect of oral propranolol during its short-term administration in thyrotoxic man.

Adult↗
PubMed1987

(-)-Propranolol and (+/-)-cyanopindolol are mixed agonists-antagonists at serotonin autoreceptors in the hippocampus of the rat brain.

The effects of (-)-propranolol, (+)-propranolol and (+/-)-cyanopindolol on the release of [3H]5-hydroxytryptamine [( 3H]5-HT) were investigated in synaptosomes from the hippocampus of the rat, depolarized in superfusion with 15 mM KCl. (-)-Propranolol, but not (+)-propranolol, inhibited in a concentration-dependent way the K+-evoked release of [3H]5-HT. (+/-)-Cyanopindolol behaved similarly but was about 10 times more potent than (-)-propranolol. The inhibitory effects of (-)-propranolol and (+/-)-cyanopindolol were prevented by the autoreceptor antagonist methiothepin. Both beta-adrenoceptor antagonists antagonized the inhibition by exogenous 5-HT of the K+-evoked release of [3H]5-HT. The data suggest that some beta-adrenoceptor antagonists may behave as mixed agonists-antagonists at the 5-HT autoreceptor. Synaptosomes in superfusion appear to be particularly suitable to study separately agonistic compared to antagonistic activity of compounds having a mixed agonist-antagonist profile.

Animals↗
PubMed1989

Chronic propranolol attenuates hypoxic pulmonary vasoconstriction in conscious rats.

Experiments were performed on conscious, chronically instrumented rats to assess the effect of chronic propranolol treatment on basal pulmonary hemodynamics and on hypoxic pulmonary vasoconstriction. Rats received either propranolol (4 mg/day) or vehicle for 31 days via implanted osmotic mini-pumps. Animals were then acutely exposed to 8% and 10% O2. Pulmonary arterial pressure (PAP), mean arterial blood pressure (MABP) and heart rate (HR) were monitored via chronically implanted catheters, and cardiac output (CO) was measured by thermodilution. Chronic administration o propranolol was associated with minimal changes in MABP, PAP and total pulmonary resistance (TPuR). However, HR and CO decreased and total systemic resistance (TSR) increased in propranolol treated rats. The acute hypoxic pulmonary vasoconstrictor response of propranolol treated rats was significantly less than that of untreated control animals. Systemic hemodynamic responses to acute hypoxia did not differ between the groups. These data indicate that chronic propranolol administration reduces the acute hypoxic pulmonary vasoconstrictor response in conscious rats, but does not alter basal pulmonary hemodynamics.

Animals↗
PubMed1984

Propranolol potentiates leukotriene D4-induced bronchoconstriction and enhances antagonism by FPL 55712.

Aerosol LTD4-induced bronchoconstriction in anesthetized, spontaneously breathing guinea pigs was potentiated by either pretreatment with propranolol or bilateral adrenalectomy, whereas bilateral vagotomy did not affect the LTD4 response. The dose-response curve describing LTD4-induced changes in dynamic lung compliance (CDYN) and pulmonary resistance (RL) [as reflective indices of bronchoconstriction] was shifted to the left by approximately 20-fold by propranolol. Against an equal degree of LTD4-induced bronchoconstriction, the leukotriene antagonist, FPL 55712, had an apparent 20-fold greater potency in propranolol-pretreated animals vis a vis saline-treated controls. The duration of action of aerosol FPL 55712 was similar in both propranolol-treated and saline-treated animals. These results demonstrate that aerosol LTD4-induced bronchoconstriction is modulated by an adrenergic compensatory bronchodilator mechanism that is apparently dependent upon the adrenals and independent of vagal influences. Inhibition of the effect of this reflex with propranolol also enhances the apparent potency of an aerosol leukotriene antagonist, FPL 55712, presumably reflecting a constant LTD4 to antagonist ratio in the saline-treated and propranolol-pretreated guinea pigs.

Adrenalectomy↗
PubMedDate not supplied

Effect of propranolol on antinociceptive and withdrawal characteristics of morphine.

Propranolol at a dose (10 mg/kg) which did not alter tail-flick latency by itself, did not alter the ED50 of morphine when given 10 min prior to the narcotic. Propranolol at doses of 10 and 25 mg/kg given 10 min prior to naloxone challenge did not significantly alter the frequency of naloxone induced jumping 72 hr after morphine pellet implantation. The ED50 of naloxone in morphine pelleted mice was not altered by treatment with propranolol at 0, 24, and 48 hr after pellet implantation. Naloxone caused hyperactivity in mice when administered 72 hr after morphine pellet implantation. An injection of 25 mg/kg propranolol 10 min prior to naloxone did not block this hyperactivity. In addition, administration of 10 mg/kg of propranolol every 8 hr to rats during withdrawal from morphine failed to alleviate the withdrawal syndrome as evidenced by changes in either body weight or water intake. These data suggest that the beta-adrenergic blocking agent, propranolol, does not alter the antinociceptive activity or lessen the withdrawal syndrome of morphine in rodents.

Analgesics, Opioid↗
PubMed1987

Involvement of brain transmitters in the modulation of shock-induced aggression in rats by propranolol and related drugs.

(+/-)Propranolol (1, 3, 10 and 30 mg/kg) exhibited a differential effect on footshock aggression (FSA) in rats. Lower doses (1 and 3 mg/kg) of the drug facilitated FSA, whereas an inhibitory effect was observed with higher doses (10 and 30 mg/kg) of the same. (+)Propranolol (30 mg/kg) and UM-272 (1 and 10 mg/kg) as well as physostigmine (0.1 and 0.5 mg/kg) all produced inhibition of FSA. Similar FSA inhibitory effects were also observed with salbutamol (1 and 5 mg/kg). Pretreatment with atropine and not methylatropine attenuated the anti-aggressive effect of (+/-)propranolol (10 mg/kg) without appreciably altering the facilitatory effect (1 mg/kg) of the drug on FSA. In addition, at the anti-aggressive doses, (+/-)propranolol (10 mg/kg) and UM-272 (10 mg/kg), significantly inhibited brain cholinesterase enzyme activity when compared to saline controls. (+/-)Propranolol (10 mg/kg) also inhibited significantly the aggression induced by reserpine-apomorphine treatment. It is inferred that a central cholinergic and dopaminergic mechanism is involved in the anti-aggressive effect of (+/-)propranolol, whereas the low dose induced facilitation of affective aggression could be attributed to central beta-adrenoceptor blockade.

Acetylcholinesterase↗
PubMed1976

A comparison of the beta-blocking activities of practolol, sotalol, and propranolol in human and guinea pig tracheal smooth muscle.

Beta adrenergic blockade was studied in vitro with human tracheal muscle strips and guinea pig tracheal chains. It was shown in isolated smooth muscle from both man and guinea pig that the order of potency for the three beta-blocking agents studied was: propranolol greater than sotalol greater than practolol. Under the conditions of this study, propranolol was about 30,000 times and sotalol about 30 times as potent as practolol. The order of potency suggests that the nature of adrenergic blockade induced by practolol on tracheal smooth muscle is only weakly beta2-relative to the blocking effects of propranolol and sotalol. Beta adrenergic blockade by propranolol, sotalol, and practolol produced different degrees of increased histamine lethality in mice. Whereas both propranolol at 0.01 mg/kg and sotalol at 1.0 mg/kg resulted in 100% histamine-induced lethality, practolol at 50 mg/kg resulted in only 50% histamine-induced lethality. These data, when added to those from our previous studies, suggest that the mechanisms responsible for resistance to the effects of histamine in untreated mice are at least partially mediated by the beta2-adrenergic system. Thus, in three different tissues, the blocking activity of practolol was shown to be less than that of sotalol or propranolol.

Animals↗
PubMed1992

Epicardial propranolol administration for ventricular arrhythmias in dogs: matrix formulation and characterization.

The effect of propranolol on the prevention of ventricular tachycardia/fibrillation (VT/VF) due to acute coronary ischaemia was studied in dogs. A series of propranolol-polymer controlled release matrices in slab configuration using various polyurethanes and a polyurethane-silicone rubber copolymer were formulated and characterized. In general, drug release in vitro occurred with an initial burst phase followed by an exponentially declining delivery rate; the silicone rubber containing copolymer preparation had more sustained release properties than did pure polyurethane matrices. In the animal studies, dogs underwent 5-hourly 10 min complete occlusions of the left anterior descending coronary artery (LAD), followed by 50 min normal perfusion. During non-drug occlusions VT occurred at a frequency of 1.22 +/- 0.12 episodes/min. A propranolol-polyurethane matrix (30% w/w, 28-42 mg) was placed on the ischaemic zone of the left ventricular epicardium immediately after the fifth occlusion. After an hour of drug delivery a sixth occlusion took place. The number of arrhythmia episodes both before and after drug were quantified and compared. The time to ventricular fibrillation (when present) and the mean blood pressure were also assessed. The drug patch delivered propranolol at a dose of 140 +/- 45 micrograms/kg by the conclusion of the 1 h study period. Therapeutic drug levels were achieved in the peripheral blood samples (8.7-43.7 ng/ml) and were enhanced in coronary venous samples (360.9-556.2 ng/ml). Reduction of blood pressure and proarrhythmic events following epicardial controlled release propranolol administration were noted but were not statistically significant. Arrhythmia episodes before and after propranolol were not found to be significantly different (VT/min 1.02 +/- 0.31 and 1.22 +/- 0.12).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗