The cardiac effects of amiloride, a potassium-sparing diuretic, were investigated in isolated, blood-perfused atrioventricular (AV) node, sinoatrial (SA) node, and papillary muscle preparations of dogs. In AV node preparations, when infused into the posterior septal artery (which supplies mainly the AV node), amiloride in a blood concentration of 0.2 mumole/ml gradually prolonged the functional refractory period at atrial pacing rates of 100, 150, and 200 stimuli/min. The lower the pacing rate, the greater was the prolongation. AV conduction time was increased only with pacing at 200 stimuli/min. In the same preparation, when infused into the anterior septal artery (which supplies the His-Purkinje-ventricular system), amiloride did not appreciably prolong AV conduction time, indicating that intraventricular conduction was unaffected. The configuration of ventricular bipolar electrograms was also unchanged. In SA node preparations, amiloride had a negative chronotropic action which was not antagonized by atropine. In papillary muscle preparations, amiloride had a positive inotropic action and prolonged the effective refractory period but did not change ventricular automaticity. The positive inotropic action of amiloride was not antagonized by carteolol, a beta-adrenoceptor-blocking agent. These results indicate that amiloride may have antiarrhythmic properties.
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