Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats.

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.

Section: Discussionmentioning

confidence: 47%

mentioning

confidence: 98%

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

“…Both types of receptors are known to exist in cardiac cells, and there is evidence for adrenergic involvement in ischaemia-related dysrhythmias (e.g. Sheridan et al, 1980). In initial experiments it was found that a combination of propranolol and phentolamine by itself caused a reduction in calcium current amplitude.…”

Section: Resultsmentioning

confidence: 99%

The effects of prenylamine on single ventricular myocytes of guinea‐pig

Shimoni

Posner²,

Spindler³

et al. 1988

1 The action of prenylamine, an antianginal drug, was studied in single ventricular guinea-pig myocytes. In concentrations of 10-50 pm, prenylamine significantly (P <0.01) shortened action potentials, and significantly (P < 0.001) reduced the inward calcium current by 29% to 76% (n = 7). This effect was also present in the presence of adrenoceptor-blockade (with phentolamine and propranolol), and was thus not due to indirect changes in endogenous catecholamine action. 2 Prenylamine did not affect the steady state level of current at the end of long pulses, and does therefore not act by changing time-dependent outward currents. Since the resting potential in the unclamped mode is unchanged during gross changes in action potential duration, it is also unlikely that there are any changes in the background, time-independent potassium conductance. 3 It is concluded that prenylamine has a direct effect on cardiac calcium channels, not mediated by adrenoceptor activation.

“…Of more physiological relevance is the finding that cardiac responses to noradrenaline may be similarly affected in the two disease states. Responses to noradrenaline or sympathetic nerve stimulation are mediated via f3-adrenoceptors in the normal heart but during ischaemia (Sheridan et al, 1980) (1987) where no significant protective effect of PTU pretreatment could be demonstrated in rats subject to reperfusion-induced arrhythmias. However the method of PTU administration was different in the two studies.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis is based on the fact that in the anaesthetized cat, the aadrenoceptor antagonists phentolamine and prazosin, were effective in preventing ventricular arrhythmias during myocardial ischaemia and reperfusion (Sheridan et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

Ventricular fibrillation is reduced in hypothyroid rats with enhanced myocardial α‐adrenoceptor responsiveness

Chess-Williams

Coker

1989

1The severity of ventricular arrhythmias induced by coronary artery occlusion and reperfusion has been examined in control rats and animals made hypothyroid by pretreatment with 6-propylthiouracil (PTU). The maximal driving frequency and sensitivity of isolated left atria and papillary muscles to isoprenaline and to phenylephrine in the presence of propranolol, were also examined in tissues from control and hypothyroid animals. 2 Pretreatment with PTU resulted in a potentiation of responses to the a-adrenoceptor agonist phenylephrine in both left atria and papillary muscles, while responses to isoprenaline were depressed in left atria but unaltered in papillary muscles from hypothyroid animals.3 In rats subject to coronary artery occlusion, PTU pretreatment reduced the incidence of ventricular fibrillation during acute myocardial ischaemia and abolished reperfusion-induced ventricular fibrillation. Mortality during myocardial ischaemia and reperfusion was also abolished. Diastolic blood pressure was similar in hypothyroid and control animals, but there was a small reduction in systolic blood pressure and a marked decrease in heart rate in PTU pretreated animals. 4 These results demonstrate that PTU-induced hypothyroidism represents a condition where cardiac a-adrenoceptor-mediated responses are enhanced but the severity of ischaemia-and reperfusion-induced arrhythmias is reduced.