Acute coronary artery occlusion-reperfusion-induced arrhythmias in rats, dogs and pigs: Antiarrhythmic evaluation of quinidine, procainamide and lidocaine

1Reperfusion-induced arrhythmias were elicited in the pentobarbitone-anaesthetized rat by occlusion of the left main coronary artery and subsequent release. 2 These arrhythmias were rapid in onset, occurring within 20 s after release of the ligature, and were of short duration (1 -2 min). Their severity was dependent upon the duration of the preceding occlusion. A 5 or 15 min occlusion period produced the most severe arrhythmias on release, the incidence of ventricular fibrillation being 56 and 50% respectively. 3 Evidence that reperfusion had occurred was provided by fluorescein dye distribution and intramyocardial temperature studies. 4 The severity of reperfusion arrhythmias and mortality was unaffected by bilateral vagotomy, P-adrenoceptor blockade by atenolol (2 mg kg-' i.v.) or a combination of the two. The incidence of reperfusion-induced ventricular fibrillation was significantly reduced by Org 6001 (which blocks the fast inward sodium current), melperone (which acutely prolongs the cardiac action potential duration) and bepridil (which blocks both fast and slow inward currents). It was unaffected by nitroglycerine and the calcium antagonists verapamil, prenylamine and nifedipine. 6 We have shown that reperfusion-induced cardiac arrhythmias can be consistently elicited in the anaesthetized rat and that they are particularly susceptible to drugs that can block the fast inward sodium current.

Section: Discussionmentioning

confidence: 99%

An investigation into the characteristics of reperfusion‐induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents

Kane

Parratt

Williams

1984

“…The rat is now frequently used for ischaemia and infarction studies (Au et al, 1979;Clark et al, 1980;Marshall et al, 1981). In conscious rats we demonstrated antiarrhythmic activity for a number of drugs Jang et al, 1983;Johnston et al, 1983b) including quinidine (Johnston et al, 1983a (Bergey et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat

Curtis

MacLeod

Walker

1984

1 The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. 2 Verapamil (2-20mgkg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-'. This dose was effective when given immediately post-occlusion. 3 Severe arrhythmias, as opposed to PVC, were preferentially reduced. 4 In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20mgkg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. 5Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre-or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 + 0.8 ltmol -1 and 0.6±0.1 Mmoll-1 (x±s.e.mean), respectively following post-occlusion administration vs. 2.7 ± 1.2 and 0.24 ± 0.04 for pre-occlusion administration. 6 Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ 7 We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.

“…All 3 drugs tested in the present experiments suppressed reperfusion arrhythmias in the rat. Quinidine was found previously to exert this effect not only in rats but also in dogs and pigs (Bergey et al, 1982). There does not seem to be a previous study of the activity of bethanidine in this situation, but Wastila et al (1981) showed that meobentine suppressed reperfusion arrhythmias in the dog.…”

Section: Discussionmentioning

confidence: 95%

“…Pretreatment with bethanidine, meobentine or quinidine reduced the duration of these arrhythmias in the present experiments. Previous workers have shown that quinidine protects against various ischaemia-induced arrhythmias in the rat heart (Kane et al, 1981;Bergey et al, 1982;Johnston et al, 1983), the dog heart (Stephenson et al, 1960;Bergey et al, 1982) and the pig heart (Bergey et al, 1982). Although bethanidine has been found to protect recently infarcted myocardium against certain electrically-induced arrhythmias (see Introduction), the effect against spontaneous arrhythmias occurring in the recently infarcted heart does not seem to have been demonstrated before.…”

Section: Discussionmentioning

confidence: 98%

A comparison of the effects of bethanidine, meobentine and quinidine on the electrical activity of rat hearts in vivo and in vitro

Northover

1985

Polytechnic, Leicester LEI 9BH 1 Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments of the right ventricular free wall of the rat heart during superfusion and electrical stimulation in vitro at 37°C. 2 The sulphates of bethanidine, meobentine or quinidine (4 to 20riM) applied in vitro caused a prolongation of action potential duration and a delayed and slowed return of electrical excitability following an action potential. 3 Intracardiac electrical stimulation of the urethane-anaesthetized rat heart in situ was used to measure ventricular refractory periods from the electrocardiogram. 4 Intravenous administration of bethanidine, meobentine or quinidine (10 to 20mg kg-')caused a prolongation ofventricular refractory periods. Quinidine had a briefer duration ofaction than either of the other two drugs tested. 5 Urethane-anaesthetized open-chested rats which were subjected to left coronary artery occlusion displayed ventricular tachyarrhythmias in their electrocardiogram. These arrhythmias occurred during the period of occlusion and even more prominently after release of the occlusion. Intravenous administration of bethanidine, meobentine or quinidine (I to 20 mg kg-') protected rats against these arrhythmias. The protective effect of quinidine was briefer than that of either of the other two drugs tested.