The intravenous administration of naloxone 15 min before acute coronary artery ligation in both anaesthetized and conscious male rats markedly reduced the incidence and severity of the ventricular arrhythmias that occur within 30 min of the onset of myocardial ischaemia. The incidence of ventricular fibrillation was especially reduced and, in conscious rats, the survival 16 h after ligation was increased from 27% (in the controls) to 58 and 73% after 2 and 4 mg/kg naloxone respectively. One possible explanation of these results implies a detrimental effect of released endorphin in the early stages of myocardial ischaemia.

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In male rats, anaesthetized with pentobarbitone, ligation of the main left coronary artery causes an early phase of ventricular arrhythmias which last about 30 min. In approximately 60% of control animals, ventricular fibrillation occurs but since spontaneous reversion to sinus rhythm may occur, mortality is of the order of 30%. When administered intravenously 15 min prior to ligation, verapamil (0.01 and 0.05 mg kg−1), prenylamine (0.5 mg kg−1), flunarizine (0.1, 0.25, 0.5 and 1.0 mg kg−1) and cinnarizine (0.25, 0.5 and 1.0 mg kg−1) protected against these arrhythmias. Higher doses of verapamil (0.1 and 0.5 mg kg−1), prenylamine (5 mg kg−1) and flunarizine (2.5 mg kg−1) did not afford a similar protection and mortality was increased to or above control values. Death was due in prenylamine‐treated rats to atrioventricular block leading to asystole whereas in those administered verapamil or flunarizine it was a consequence of persistent ventricular fibrillation. Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine. Heart rate was reduced by administration of only the highest dose of prenylamine. These studies show that although the four calcium antagonists studied, i.e. verapamil, prenylamine, flunarizine and cinnarizine do suppress ischaemia‐induced arrhythmias, this protective effect may be limited to a narrow concentration range.

1The intravenous administration, to anaesthetized rats, of meptazinol (1 and 2 mg kg-1), a partial agonist at opiate receptors, greatly reduced the incidence of ventricular extrasystoles that resulted from acute coronary artery occlusion. The incidence of ventricular fibrillation (VF) was reduced from 50% (in the controls) to 10% and the mortality from 30% to zero. 2 In similar doses, pretreatment with meptazinol also reduced ventricular arrhythmias, including fibrillation, in conscious rats subjected to coronary artery occlusion. In this model, survival at 16 h was increased from 27% in the controls to 50% and 83% respectively in rats pretreated with 1 and 2 mg kg-I of the drug. 3 In antiarrhythmic doses, meptazinol had little effect on either heart rate or systemic arterial blood pressure. 4 Intracellular action potential recordings from papillary muscle removed from rats given meptazinol (2 mg kg-1) 15 min previously showed an increase in APD50 and APD90 of more than 40%.There was no effect on dV/dt6,,. When superfused with meptazinol in vitro normal rat papillary muscle stimulated at 1 or 3 Hz showed an increase in APD90 and a decrease in d V/dtma,. 5The antiarrhythmic effect of meptazinol in these models can probably be explained by direct actions on the cardiac muscle action potential (increase in APD) although effects on opiate receptors cannot be ruled out. It is suggested that meptazinol might be useful in relieving pain, and in reducing the severity of arrhythmias in the early stages of acute myocardial infarction.

The oral administration to rats of the calcium antagonists nifedipine, nisoldipine and niludipine (3 mg/kg, 1 —1.25 h before acute coronary ligation) greatly reduced the duration of ventricular tachycardia and fibrillation (VF) occurring in the first 30min post‐ligation period. The duration of VF was especially reduced (by 74–92%). None of the animals so treated died compared with a 40% mortality in the controls.

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Gl 1XW1 Pretreatment of anaesthetized rats with intravenously administered lidoflazine (an antianginal agent) reduced the incidence and severity of ventricular arrhythmias which resulted from acute coronary artery ligation. Ventricular fibrillation was completely prevented by doses of 50 pg/kg and 2 mg/kg and no animal so treated died (contrast 50% incidence of fibrillation in the controls and 30% mortality). 2 In anaesthetized greyhound dogs, lidoflazine (2 mg/kg) administration resulted in transient reductions in systemic arterial pressure, LV dP/dt max and cardiac output. Coronary sinus P02 was markedly increased, indicating pronounced coronary vasodilatation. 3 Lidoflazine pretreatment inhibited the increase in epicardial ST-segment elevation which resulted, in dogs, from short (3 min) occlusions of the left anterior descending coronary artery. This effect was especially marked at sites where, in control occlusions, ST-segment elevation was most pronounced. 4 Lidoflazine greatly reduced the number of ventricular ectopic beats which usually resulted from more prolonged (30 min) periods of acute coronary artery occlusion. There was no ventricular fibrillation in these dogs (contrast 25% incidence in the controls). (1980). There has been renewed interest in lidoflazine because of the evidence that it protects cardiac muscle against the deleterious effects of ischaemia and subsequent reperfusion (Nayler, 1980; Flameng, Daenen, Xhonneux, Van de Water & Van Belle, 1980;Flameng, Daenen, Borgers, Thone, Xhonneux, Van de Water & Van Belle, 1981). The mechanism of this protection is unclear but lidoflazine interferes with the slow channel transport of Ca2+, at least in smooth muscle, and it is possible that lidoflazine alleviates myocardial damage, at least in part, by preventing mitochondrial calcium overload (Flameng et al., 1981).Despite some evidence (de Geest, Kesteloot & Piessens, 1979) that prolonged treatment with lidoflazine is of some benefit in the long term management of patients following myocardial infarction, little is known about the effects of the drug on the 0007-1188/82/060347-08 $01.00 early life-threatening ventricular arrhythmias which are a consequence of acute myocardial ischaemia. Schaper, Xhonneux, Jageneau & Janssen (1966) showed in dogs that prolonged oral treatment with the drug reduced the incidence of ventricular fibrillation following abrupt coronary artery occlusion whereas Carmeliet & Xhonneux (1971) found that lidoflazine was ineffective in reversing ventricular arrhythmias 24 h after coronary artery ligation. The aim of the present studies was three fold. Firstly to determine whether lidoflazine is effective against the early life-threatening arrhythmias that occur soon after coronary artery occlusion. Secondly, to determine if it reduces the incidence of arrhythmias following reperfusion and thirdly to examine, using epicardial mapping techniques, whether lidoflazine reduces the severity of myocardial ischaemic damage. Methods Studies in anaesthetized ratsThe effect of lidoflazine...

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