The Effects of Sotalol and Propranolol on Contractile Force and Atrioventricular Conduction Time of the Dog Heart In Situ

Hoffmann, Richard P.; Grupp, Günter

doi:10.1378/chest.55.3.229

Cited by 35 publications

(6 citation statements)

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“…Practolol had 40% of the potency of propranolol in protecting guinea-pigs against ouabain-induced ventricular fibrillation (Papp & Vaughan Williams, 1969b). The ratios of the activities of MJ 1999 and propranolol as p-adrenoceptor blocking agents in animals have been variously reported as 1/11 (Levy & Richards, 1965), 1/17 (Raper & Wale, 1968), 1/3 to 1/4 (Farmer & Levy, 1968a, b), 1/5 (Hoffmann & Grupp, 1969), and 1/3 (Aberg, Dzedin, Lundholm, Olsson & Svedmyr, 1969). In man the activities of propranolol and of MJ 1999 are nearly equal, especially after oral dosage (Lish, Shelanski, Labudde & Williams, 1967;Frankl & Soloff, 1968;Kofi Ekue, Lowe & Shanks, 1970;Svedmyr, Jakobsson & Malmberg, 1969;Svedmyr, Malmberg & Haggendal, 1970).…”

Section: Resultsmentioning

confidence: 99%

“…This would be consistent with our finding that MJ 1999 prolonged the action potential in both tissues, because, whereas prolonged depolarization increases contractions in ventricular muscle (Kavaler, 1959), in atrial muscle it does not (Kavaler, 1960). Hoffmann & Grupp (1969), however, reported that MJ 1999 reduced ventricular contractile force in anaesthetized dogs, both reserpinized and non-reserpinized. Negative inotropic effects of MJ 1999 on myocardial contractions in animals were also reported by Folle & Aviado (1965) and by Stanton, Kirchgessner & Parmenter (1965), and a hypotensive effect was reported by Farmer & Levy (1968b) in dogs, but not in hypertensive rats (Farmer & Levy, 1968a).…”

Section: Inotropic Actionmentioning

confidence: 94%

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A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

Singh

Williams

1970

British J Pharmacology

383

127

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Summary Both MJ 1999 and AH 3474 protected guinea‐pigs anaesthetized with urethane against ouabain‐induced ventricular fibrillation. MJ 1999 had 1/90, and AH 3474 1/30, of the activity of procaine in reducing the height of the action potential of frog sciatic nerve. MJ 1999 and AH 3474 reduced the rate of rise of intracellularly recorded action potentials at concentrations in excess of 160 × 10−6m (50 mg/l.). It was concluded that direct depression of depolarization could have contributed little to the protection against ouabain‐induced fibrillation. MJ 1999, but not AH 3474, greatly prolonged the duration of the action potential in acute experiments on isolated atrial and ventricular muscle, and prolonged the Q‐Tc interval of the electrocardiogram in anaesthetized guinea‐pigs. It is suggested that this effect contributes to anti‐arrhythmic activity. At concentrations up to 80 × 10−6m AH 3474 had positive chronotropic and inotropic effects on isolated rabbit atrial muscle, but at higher concentrations these were superseded by negative effects. MJ 1999 was depressant at all concentrations studied, the threshold concentrations being 19 × 10−6m for chronotropic, and 162 × 10−6m for inotropic effects.

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Section: Resultsmentioning

confidence: 99%

Section: Inotropic Actionmentioning

confidence: 94%

A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

Singh

Williams

1970

British J Pharmacology

383

127

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“…6 mg/kg dose. Cardiac index likewise decreased in similar proportions in all patients except Circulation, Volume XLII, of intravenously administered sotalol on stroke index and left ventricular enddiastolic pressure (LVEDP).…”

mentioning

confidence: 99%

Sotalol-Induced Beta Blockade in Cardiac Patients

et al. 1970

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Sotalol (MJ 1999), a beta-adrenergic blocking agent found to have no significant intrinsic myocardial depressant effects, was adnministered intravenously to 20 patients with heart disease. Eight of the patients had clinical and hemodynamic evidence of chronic heart failure. Doses ranged from 0.2 to 0.6 mg/kg.In all studies, heart rate decreased significantly, accompanied by comparable decreases in cardiac index and tension-time index. There were, however, no significant changes in stroke index, mean blood pressure, or left ventricular end-diastolic pressureeven in those patients with advanced heart failure, indicating that the changes noted were primarily rate-related and could not be ascribed to myocardial depression. To confirm this, further studies were performed in which heart rate was held constant by atrial pacing in normal and catecholamine-depleted dogs. Sotalol, at doses much higher than the minimal beta-blocking dose, did not change stroke index, blood pressure, left ventricular end-diastolic pressure, or estimated maximal velocity of isotonic shortening (Vmax), confirming that myocardial contractility was unaffected.It is concluded that sotalol-induced beta blockade had no observable myocardial depressant action in dogs or adverse hemodynamic effects in cardiac patients, even when advanced chronic heart failure was present.

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“…Systolic dysfunction may be present in dogs affected with ventricular arrhythmias secondary to, for example, arrhythmogenic right ventricular (RV) cardiomyopathy, dilated cardiomyopathy (DCM), tachycardia‐induced cardiomyopathy, ischemia, or myocarditis. However, in dogs, the negative inotropic effect of sotalol (because of β–blockade) appears to be modest (ie, approximately one‐fifth the negative inotropic effect of propranolol) . Also, 2 independent studies in healthy anesthetized dogs using invasive indices of left ventricular (LV) systolic function (+dP/dt) demonstrated that the negative inotropic effect of sotalol is attenuated or balanced by enhanced contractility secondary to prolonged action potential duration and hence, prolonged time for calcium entry .…”

Section: Introductionmentioning

confidence: 99%

“…However, in dogs, the negative inotropic effect of sotalol (because of bblockade) appears to be modest (ie, approximately one-fifth the negative inotropic effect of propranolol). 3 Also, 2 independent studies in healthy anesthetized dogs using invasive indices of left ventricular (LV) systolic function (1dP/dt) demonstrated that the negative inotropic effect of sotalol is attenuated or balanced by enhanced contractility secondary to prolonged action potential duration and hence, prolonged time for calcium entry. 4,5 Based on these studies, the clinical impact of sotalol administration on systolic function in dogs with ventricular arrhythmias may be negligible, but has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Acute echocardiographic effects of sotalol on ventricular systolic function in dogs with ventricular arrhythmias

Visser

Kaplan

Nishimura

et al. 2018

Veterinary Internal Medicne

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BackgroundSotalol is a commonly used antiarrhythmic drug that may alter ventricular function.ObjectiveTo determine the effect of sotalol on echocardiographic indices of ventricular systolic function in dogs with ventricular arrhythmias.AnimalsThirty‐five client‐owned dogs with ventricular arrhythmias.MethodsDogs with ventricular arrhythmias (n = 27) had an echocardiogram and 5‐minute ECG performed at baseline and 2‐4 hours post‐sotalol (2‐2.5 mg/kg PO once). Eight additional dogs underwent the same protocol but did not receive sotalol (within‐day variability controls). Left ventricular (LV) internal dimension at end‐systole normalized to bodyweight (LVIDs_N), LV ejection fraction (LV EF), LV shortening area, LV fractional shortening, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic myocardial velocity were evaluated as indices of systolic function.ResultsAll indices except TAPSE had mild decreases in systolic function post‐sotalol (all P ≤ .0007) compared with baseline but only the percent change in LVIDs_N and LV EF were significantly (P ≤ .0079) different from the percent change of the same indices in control dogs. Sinus heart rate, ventricular premature complexes/5‐minutes, and arrhythmia grade also were decreased post‐sotalol (all P ≤ .01) compared with baseline when assessed by a 5‐minutes ECG. No dog experienced an adverse event post‐sotalol, including dogs with systolic dysfunction or atrial enlargement.Conclusions and Clinical ImportanceA single dose of sotalol may cause a mild decrease in LV systolic function in dogs with ventricular arrhythmias. Sotalol appears to be well tolerated, even in dogs with atrial enlargement or systolic dysfunction.

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The Effects of Sotalol and Propranolol on Contractile Force and Atrioventricular Conduction Time of the Dog Heart In Situ

Cited by 35 publications

References 3 publications

A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

Sotalol-Induced Beta Blockade in Cardiac Patients

Acute echocardiographic effects of sotalol on ventricular systolic function in dogs with ventricular arrhythmias

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