In control anaesthetized baboons subjected to 30 min occlusion of the left anterior descending coronary artery, followed by 5.5 h reperfusion, total plasma levels for creatine kinase (CK) and lactate dehydrogenase (LDH) were markedly elevated in a time-related manner. In a second group of baboons pretreated 10min prior to ischaemia with ranolazine [(±+N{2,6-dimethyl-phenyl)-4[2-hydroxy-342-methoxyphenoxy)propyl]-1-piperazine acetamide dihydrochloride; RS43285-193] at 500pgkg-1 i.v., followed by continuous infusion of SO gkg-1 min-1, neither enzyme was significantly elevated at any time point.Similarly, serum levels of the cardiospecific isoenzyme CK2 were 8 fold greater in the controls than in the ranolazine-treated animals at 6h. The results indicate that ranolazine pretreatment abolished cardiac enzyme release over a 5.5 h reperfusion period, indicating a potential protective effect.

1 A pentobarbitone-anaesthetized canine model ofmyocardial conduction was developed to evaluate drug effects on intra-atrial (I-A), intra-ventricular (I-V) and atrioventricular (A-V) conduction parameters, both at rest and during electrical pacing of the right atrium or ventricle. Drug effects on the ability of the sino-atrial (SA) node to re-establish sinus rhythm on switching off electrical pacing were also considered. The effects of the novel anti-anginal compound RS 43285-193 ((± )-N-(2,6-dimethylphenyl)-4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-l-piperazine acetamide dihydrochloride) were compared to those of the standard anti-anginal compounds nicardipine, nifedipine and verapamil.2 In the dose range 15-7000pgkg-', RS43285 had no significant effects on I-A, I-V or A-V conduction either at rest or during electrical pacing and did not affect the re-establishment of sinus rhythm. 3 Nicardipine had no effects on conduction parameters at resting heart rate. There were no effects on

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1 An anaesthetized canine model of transient myocardial ischemia (TMI) has been developed in which reproducible and reversible electrocardiographic (ECG) and haemodynamic responses are exacerbated by electrical pacing. 2 The model could separate the ECG and haemodynamic effects of compounds with antiischaemic properties. 3 Compounds known to possess peripheral or coronary vasodilator properties did not necessarily alleviate the ECG consequences of TMI since glyceryl trinitrate was active whereas dipyridamole was not. The effects of verapamil were complicated by its adverse conduction effects while lidoflazine inhibited the ECG changes only during the ischaemic phase and the 'metabolic modulator' oxfenicine worsened the ECG response. 4 In a model considered to lack coronary reserve, improvements observed in the ischaemic ECG and global ventricular function were considered to result from a direct myocardial effect of the drugs examined rather than by a vascular influence. This was provided to the greatest degree by the Ca2 +-entry blockers nifedipine and nicardipine, with flunarizine adopting an intermediate position.

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