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) is a chemically novel agent which exhibits in a single molecule both angiotensin converting enzyme (ACE) inhibition and P-adrenoceptor-blocking properties.2 BW A575C produced a competitive blockade of heart rate responses to isoprenaline in a guinea-pig right atrial preparation (pKB 7.18 ± 0.05, cf. pindolol 8.9 ± 0.7). BW A575C inhibited a partially purified preparation of ACE obtained from rabbit lung (IC50 10.7 + 2.1 nM, cf. enalaprilat, 4.4 ± 0.8 nM).3 Intravenous administration of BW A575C (1-100 tgkg-' min-')to the pithed rat inhibited in a dose-dependent fashion both angiotensin I-induced pressor responses and isoprenaline-induced tachycardia. Dose-ratios obtained from such studies demonstrated that, in this preparation, BW A575C was approximately 100 times more active as an ACE inhibitor than as a P-adrenoceptor blocking agent. 4 Intravenous administration of BW A575C (I mg kg-') to the conscious rat inhibited angiotensin Iinduced pressor responses, being approximately equipotent to enalapril and 10 times more potent than captopril. At the same dose, BW A575C had a similar duration of action as an ACE inhibitor to enalapril. 5 Intravenous administration of BW A575C (I mg kg-') to either conscious dogs or rats inhibited both angiotensin I-induced pressor responses and isoprenaline-induced heart rate responses. Doseratios obtained from such studies demonstrated that in these species, BW A575C was 2-10 times more active as an ACE inhibitor than as a P-adrenoceptor blocking agent.

1 BW A256C (5(3)-amino-6-(2,3-dichlorophenyl)-2,3(2,5)-dihydro-3(5)-imino-2-isopropyl-1,2,4-triazine) is a novel class 1 antiarrhythmic agent designed to combine the features ofpotency with reduced central nervous system penetration. 2 BW A256C reduced the maximum rate of depolarization of guinea-pig ventricle and dog Purkinje fibres in vitro (EC5o, 2.2 x 10-6 M and 1.8 x 10-6 M, respectively), being significantly more potent than quinidine, lidocaine, disopyramide and flecainide. BW A256C was also more potent than these agents at inhibiting aconitine-induced arrhythmias in anaesthetized rats; however, unlike these agents, BW A256C was devoid of hypotensive activity at antiarrhythmic doses. 3 In anaesthetized dogs, intravenous administration of BW A256C (0.25-1 mg kg-') caused a dosedependent suppression of ventricular arrhythmias that occurred on reperfusion of an occluded coronary artery. 4In conscious dogs, intravenous infusion (total dose, 1.5 mg kg 1) or oral administration of BW A256C (1.25-5mg kg-') caused dose-dependent suppression of the ventricular ectopic activity that occurred following 20-24 h of permanent coronary artery ligation. 5In the conscious dog, BWA256C was approximately 7 times more potent and was also longer acting than flecainide. 6 Administration of BW A256C was not associated with any evidence of peripheral or CNS toxicity. However, plasma levels 3-4 times greater than the antiarrhythmic levels were associated with a proarrhythmic activity.

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t-PA consistently achieved main vessel reperfusion within 40 min (mean) of instituting therapy in our model, leading to marked salvage of ischaemic myocardium. The data also suggest that maintenance infusion of t-PA helps preserve microvascular coronary flow throughout reperfusion and tends to reduce infarct size further.