The effects of prolonged  -adrenoceptor blockade on heart weight and cardiac intracellular potentials in rabbits

Williams, E. M. Vaughan; Raine, A. E. G.; Cabrera, Arturo Augusto Cano; Whyte, John

doi:10.1093/cvr/9.5.579

Cited by 70 publications

(10 citation statements)

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“…Investigations in animals of the cellular effects of prolonged /J-blockade were begun several years ago, and it was shown that treatment of young rabbits for several weeks with /?-adrenoceptor blocking drugs at doses comparable with those used clinically had a number of secondary effects which could be distinguished from the acute actions of the drugs (Vaughan Williams et al, 1975;Raine and Vaughan Williams, 1980). Atrial transmembrane action po-tential duration was greatly prolonged, a surprising finding since, in acute experiments, /8-blockers either have no effect on action potential duration or shorten it, in both atrial (Papp and Vaughan Williams, 1969) and ventricular muscle (Davis and Temte, 1968).…”

mentioning

confidence: 99%

Adaptation to prolonged beta-blockade of rabbit atrial, purkinje, and ventricular potentials, and of papillary muscle contraction. Time-course of development of and recovery from adaptation.

Raine¹,

Williams²

1981

Circulation Research

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Groups of littermate rabbits were treated for various periods up to 6 weeks with twice daily subcutaneous injections of saline, D-propranolol, DL-propranolol, or metoprolol, the latter two at doses equivalent to those used in clinical therapy. Investigations were made at a sufficient time (20-24 hours after the most recent dose) to ensure that the drugs would have been eliminated from the body, so that any observed changes would represent an adaptation to treatment, not effects due to the presence of the drugs. The ECG was recorded in vivo at regular intervals during treatment. After several days, Q-Tc was prolonged by the beta-blockers, reaching a peak effect at about 3 weeks from the start of treatment, and returned to control values at 3 weeks after cessation of treatment. Action potential duration, measured in vitro by intracellular recording, was also prolonged uniformly in atria and ventricles over a similar time-course, unrelated to cardiac frequency, but shortened in distal Purkinje cells. Peak tension was not altered in propranolol-adapted papillary muscles, but the relationship of rate of rise of tension was steeper. It is concluded that these effects represent a myocardial adaptation to prolonged beta-blockade.

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confidence: 99%

Adaptation to prolonged beta-blockade of rabbit atrial, purkinje, and ventricular potentials, and of papillary muscle contraction. Time-course of development of and recovery from adaptation.

Raine¹,

Williams²

1981

Circulation Research

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“…One of the anti arrhythmic properties of other beta blockers may be their ability to antagonize the effects of catecholamines on automaticity and conductivity, but the effects on the ventricular repolarization are to some extent controver sial. Several beta-blocking agents with different pharma cological properties produce a moderate prolongation of the ventricular repolarization time after long-term thera py, as shown in animal studies [12,13]. The lack of an acute class III effect was recently confirmed in a study with healthy volunteers, in whom metoprolol prolonged the right ventricular repolarization time by 6-8 % after 5 weeks of treatment with 400 mg daily, while no effect could be demonstrated after acute administration [7].…”

Section: Discussionmentioning

confidence: 99%

Ventricular Repolarization Time - Effect of Chronic Beta Blockade with Class II and/or Class III Properties

Blomström‐Lundqvist¹,

Jönsson²,

Edvardsson³

1988

Am J Noninvas Cardiol

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A double-blind, crossover study was performed in 20 postinfarction patients to compare the effects of chronic treatment with metoprolol (100 mg twice daily) and sotalol (160 mg twice daily) on the ventricular repolarization time. QRST intervals were measured at a fixed paced cycle length of 800 ms using transesophageal atrial stimulation. Sotalol prolonged the Q-T and J-T intervals 5-8 % more than metoprolol. The prolongation was confined to the J-T interval and thus reflects a change in the repolarization time, since no change was seen in the Q-S interval. The QTT (from the Q wave to the top of the T wave) and QTE (from the Q wave to the end of the T wave) showed consistent changes, which implies that the former may be used with advantage when the end of the T wave is difficult to define. Metoprolol and sotalol in the doses selected were found to be equipotent regarding beta blockade, as judged by the measurements of heart rate and blood pressure at rest and during bicycle exercise tests, respectively. The clinical relevance of the additional effect of sotalol on the ventricular repolarization time regarding ventricular arrhythmias in a postinfarction population is still to be established.

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“…Evemy et al [ 14] and Vaughan Williams et al [15] treated young rabbits with intraperito neal or subcutaneous propranolol and not ed a significantly reduced growth rate per haps related to a reduction in food intake.…”

Section: Discussionmentioning

confidence: 99%

“…young rabbits given propranolol [14,15] and in infants of mothers treated during preg nancy with long-term propranolol [16]. The present study was designed to evaluate the effect of chronic propranolol on the body growth and organ size of newborn beagle puppies.…”

Section: Introductionmentioning

confidence: 99%

Effect of Chronic Propranolol on Growth of Newborn Beagle Puppies

Adelman¹,

Wright²,

Spangler³

1988

Dev Pharmacol Ther

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To evaluate the effect of chronic propranolol on body growth and organ size, newborn beagle puppies were assigned to each of three treatment groups: high propranolol (18 mg/kg/day); low propranolol (6 mg/kg/day), and control. Heart rate and systolic blood pressure were significantly lower in animals receiving propranolol (p < 0.001). There were no significant differences between groups at any time during the 6 months of observation in length, weight and necropsy wet weights or histology of brain, heart, kidney, lung, liver, thyroid, pancreas, adrenal, pituitary, prostate or gonad, or in humerus and femur length. Chronic propranolol therapy had no apparent effect on body growth and individual organ size of normal newborn beagle puppies.

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The effects of prolonged -adrenoceptor blockade on heart weight and cardiac intracellular potentials in rabbits

Cited by 70 publications

References 0 publications

Adaptation to prolonged beta-blockade of rabbit atrial, purkinje, and ventricular potentials, and of papillary muscle contraction. Time-course of development of and recovery from adaptation.

Adaptation to prolonged beta-blockade of rabbit atrial, purkinje, and ventricular potentials, and of papillary muscle contraction. Time-course of development of and recovery from adaptation.

Ventricular Repolarization Time - Effect of Chronic Beta Blockade with Class II and/or Class III Properties

Effect of Chronic Propranolol on Growth of Newborn Beagle Puppies

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