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Flecainide acetate is a new antiarrhythmic drug which suppresses different kinds of experimental arrhythmias. We studied the efficacy of flecainide acetate on reperfusion- and barium-induced ventricular tachyarrhythmias in the isolated perfused rat heart by monitoring heart rate, coronary flow rate, left ventricular systolic pressure, dp/dtmax, and the voltage of the epicardial electrogram. Seventy-five male rats were randomized into 5 groups. In group I, after a 15 min period of stabilization, hearts were perfused by ischemic perfusion and then reperfused. In group II, flecainide acetate (10(-6) M) was given after stabilization and before ischaemic perfusion. In group III, barium chloride (10(-3) M) was given after stabilization. In group IV, flecainide acetate was given after stabilization and before barium chloride administration. In group V, acetylcholine chloride (10(-6) M) was given after stabilization and before barium chloride administration. In group I, we noted during ischemia a reduction in heart rate, coronary flow rate, left ventricular systolic pressure and dp/dtmax and an increase in the voltage of the epicardial electrogram. In group II, after administration of flecainide acetate, we observed a reduction in heart rate, left ventricular systolic pressure and dp/dtmax; during the ischaemic period there was no difference in these parameters with respect to group I. Reperfusion induced ventricular arrhythmias in 12 out of 15 hearts in group I and in only 3 out of 15 in group II (p less than 0.005). Barium induced ventricular arrhythmias in the 15 hearts studied in group III as well as in group IV. On the contrary, acetylcholine chloride in group V prevented the occurrence of barium-induced ventricular arrhythmias (p less than 0.005 vs group III and IV). Thus, flecainide acetate is able to reduce reperfusion-induced ventricular arrhythmias, but is unable to reduce barium-induced ventricular arrhythmias, presumably because of a different mechanism of these two types of arrhythmias.

Using the guinea-pig wheal preparation for determining the degree of infiltration anaesthesia, lignocaine was found to be 2 times more potent than levamisole. Lignocaine was, however, 1.27 times more toxic than levamisole in the mouse. It is suggested that levamisole could be used as a local anaesthetic agent for infiltration anaesthesia. As regards surface anaesthesia, lignocaine was 16.6 times more potent than levamisole. Levamisole would, therefore, not be of use in surface anaesthesia. Levamisole was more effective than lignocaine in protecting toads against deaths due to the minimum dose of ouabain which caused 100% mortality. The therapeutic indices for levamisole and lignocaine were 4.57 and 1.58 respectively. Unlike with lignocaine it was possible to achieve more than 50% protection with levamisole. Levamisole was, however, only marginally more effective than lignocaine in reverting to sinus rhythm, barium chloride-induced ventricular dysrhythmia in the rat. It is suggested that levamisole could have potential value as an antiarrhythmic agent.

The spasmolytic activity of six commonly used benzodiazepines was investigated on isolated guinea-pig ileum preparation. All six substances proved to be non-competitive antagonists of carbachol and barium chloride, the pD'2 values ranging between 3.23 and 4.37 in the presence of either agonist. The significance of these findings is discussed.

To identify the mode of action of prazosin, its effects on isolated human vascular preparations were studied. Isometric tension was recorded from spiral strips of dorsal metacarpal veins, common palmar digital arteries and uterine, splenic and ileocolic arteries. Prazosin was a potent antagonist of noradrenaline, but not 5-hydroxytryptamine or barium chloride in the metacarpal veins. Higher concentrations of prazosin were necessary to antagonize noradrenaline in the visceral arteries. The digital arteries were resistant to its sympatholytic effect. It is concluded that prazosin acts as an alpha-adrenoceptor antagonist of different potency in various vascular beds. It is postulated that the initial cardiovascular side effects of prazosin are due to venous pooling and that the long term antihypertensive effect is the result of reduced peripheral resistance because of interference with arterial sympathetic tone.