Identification of Receptor Mechanism Mediating Epinephrine-induced Arrhythmias during Halothane Anesthesia in the Dog

Maze, Mervyn; Smith, Christopher M.

doi:10.1097/00000542-198310000-00009

Cited by 67 publications

(31 citation statements)

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“…The present study demonstrated significant antiarrhythmic effects with both UK-52046 (3.8 + 1.4 igkg-') and atenolol (14.6 + 2.1 ugkg-') in this model. Furthermore, when used in combination the two drugs appear synergistic (dose of each 0.36 + 0.1 igkg-1), supporting previous studies, showing potentiation of antiarrhythmic activity with combined a-and f-adrenoceptor antagonists in the halothane-adrenaline model (Maze & Smith, 1983).…”

Section: Discussionsupporting

confidence: 84%

“…However, in a recent study investigating the effects of prazosin and metoprolol in this model, it was discovered that f,-blockade by metoprolol was significantly less effective than a1-blockade afforded by prazosin (Maze & Smith, 1983), nor was the effect of prazosin related to haemodynamic changes as sodium nitroprusside was found to be ineffective in abolishing the arrhythmia despite producing a similar fall in blood pressure. The present study demonstrated significant antiarrhythmic effects with both UK-52046 (3.8 + 1.4 igkg-') and atenolol (14.6 + 2.1 ugkg-') in this model.…”

Section: Discussionmentioning

confidence: 89%

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Effects of the myocardial‐selective α₁‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Uprichard

Harron

Wilson

et al. 1988

British J Pharmacology

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Adrenaline‐induced arrhythmias in anaesthetized dogs respired with halothane were attenuated in 3 groups of 6 dogs by either UK‐52046, 3.8 ± 1.4μgkg−1 (mean ± s.e.mean), atenolol 14.6 ± 2.1 μgkg−1, or a combination containing equal amounts of the two drugs of 0.36 ± 0.1 μgkg−1. The pressor response to adrenaline was reduced (P < 0.01) by UK‐52046 but not by atenolol or the combination of both drugs. In a group of 6 dogs with multiventricular ectopic beats 24 h after coronary artery ligation (CAL), UK‐52046, 32μgkg−1, increased the number of sinus beats in each 5min period from 137 ± 47 to 662 ± 99 (P < 0.01); this was associated with a significant (P < 0.01) fall in blood pressure. Atenolol in doses of up to 800μg kg−1 had no effect. UK‐52046, 3.7 ± 1.4μgkg−1, prevented adrenaline‐induced arrhythmias 3–4 days after CAL in 6/6 conscious dogs; atenolol in doses of up to 100μgkg−1 produced an 84.4 ± 7.4% reduction in the number of ventricular ectopic beats. A combination containing 3.7 ± 1.1 μgkg−1 of each drug prevented the arrhythmia in 6/6 dogs. The pressor response to adrenaline was attenuated (P < 0.05) by UK‐52046, but resting blood pressure was unaffected by the different treatments. An increase (P < 0.01) in heart rate was associated with both UK‐52046 and the combination. Neither UK‐52046 (doses up to 64μgkg−1) nor atenolol (up to 800μgkg−1) had any effect upon ouabain‐induced arrhythmias in 2 groups of 6 anaesthetized dogs. In a study of the early (1a/1b) arrhythmias of acute myocardial ischaemia, the total number of ventricular ectopic beats occurring within 30min of CAL was not reduced by 4μgkg−1 UK‐52046 but fell (P < 0.01 compared with placebo) after 8μgkg−1 [median values with ranges for placebo, 4μgkg−1 and 8μgkg−1 respectively 190 (4–674), 246 (9–1204) and 12 (1–154)]. Both doses of UK‐52046 were associated with significant falls in blood pressure. The arrhythmias produced by programmed electrical stimulation were studied in 2 groups of 6 conscious dogs, 7–30 days after CAL. With placebo, 4/6 dogs remained unchanged and 2 died: UK‐52046 prevented arrhythmias in 2/6, 2 remained unchanged and 2 died (P = 0.29). Compared with placebo, blood pressure fell with doses greater than 4μgkg−1. These results indicate antiarrhythmic effects of UK‐52046 in a number of experimental models and suggest an enhanced role of α‐receptors in the genesis of ischaemia‐related arrhythmias. In several of the models used, UK‐52046 produced haemodynamic changes in keeping with peripheral α‐adrenoceptor antagonism.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 89%

Effects of the myocardial‐selective α₁‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Uprichard

Harron

Wilson

et al. 1988

British J Pharmacology

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“…Alphai-adrenergic an tagonists have been reported by several in vestigators to exert antiarrhythmic activity in several experimental models of cardiac arrhythmias. [Stewart et al, 1979: Maze andSmith, 1983;Witkowski and Corr. 1984], Verapamil and D600 displace radiolabeled prazosin from cardiac membranes in vitro [Nayler et al.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Verapamil, Diltiazem and Felodipine during Experimental Digitalis-Induced Arrhythmias

Lr¹,

Rm²,

Sl³

et al. 1987

Pharmacology

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We compared the abilities of three different calcium (Ca²⁺) entry blockers, verapamil, diltiazem and felodipine to abolish ouabain-induced ventricular ectopy (100 × ectopic/total beats, VE) in anesthetized, closed-chest dogs. Ventricular tachycardia (VT) was produced in anesthetized, bilaterally vagotomized, closed-chest dogs by an average dose of 65 ± 19 μg/kg ouabain. 30 min after establishing VT, either verapamil (25–50 μg/kg + 5–10 μg/kg/min), diltiazem (50–100 μg/kg + 20–50 μg/kg/min), felodipine (3 μg/kg + 0.3 μg/kg/min) or saline was administered for another 30 min. Verapamil, at the higher dose utilized, practically abolished ouabain-induced VT (97 ± 3 to 8 ± 19% VE); diltiazem was moderately effective (96 ± 4 to 50 ± 8% ectopy) at 100 μg/kg, and felodipine exerted no antiarrhythmic effects in this model. All three Ca²⁺ entry blockers lowered mean aortic pressure, felodipine lowering this parameter most prominently. Thus, these structurally and electrophysiologically dissimilar Ca²⁺ entry blockers differed in their abilities to abolish the digitalis glycoside-induced arrhythmias in vivo. The superiority of verapamil may be related to its multiple, additional electrophysiologic effects.

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“…[24][25][26] This effect of halothane, in conjunction with sensitizing the heart to catecholamines, may facilitate AV nodal reentry and may be the mechanism which makes halothane apt to produce tachydysrhythmias. [27][28][29] Enflurane does not interfere with cardiac impulse conduction to the same degree as halothane and, in general, the heart rate remains constant. However, enflurane slows AV conduction and the QT interval is markedly lengthened.…”

Section: Cardiac Electrophysiologieal Study (Eps)mentioning

confidence: 99%

Cardiac electrophysiology and conduction pathway ablation

et al. 1993

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Identification of Receptor Mechanism Mediating Epinephrine-induced Arrhythmias during Halothane Anesthesia in the Dog

Cited by 67 publications

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Effects of the myocardial‐selective α₁‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Effects of the myocardial‐selective α₁‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Comparative Effects of Verapamil, Diltiazem and Felodipine during Experimental Digitalis-Induced Arrhythmias

Cardiac electrophysiology and conduction pathway ablation

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Identification of Receptor Mechanism Mediating Epinephrine-induced Arrhythmias during Halothane Anesthesia in the Dog

Cited by 67 publications

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Effects of the myocardial‐selective α1‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Effects of the myocardial‐selective α1‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Comparative Effects of Verapamil, Diltiazem and Felodipine during Experimental Digitalis-Induced Arrhythmias

Cardiac electrophysiology and conduction pathway ablation

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Product

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Effects of the myocardial‐selective α₁‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

Effects of the myocardial‐selective α₁‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs