Cardiovascular actions of N-allyl-clonidine (ST 567), a substance with specific bradycardic action

Abstract

In anaesthetized cats and dogs the prominent action of St 567 (1 and 2.5 mg/kg i.v.) was a decrease in heart rate. This was paralleled by a decrease in cardiac output; the decrease in blood pressure was much smaller or insignificant. The increase in heart period was mainly due to a prolongation of the diastolic period, the increase in ejection time was much smaller and of shorter duration. In cats the “triple product” of heart rate × ejection time × blood pressure was decreased by St 567. Cumulative injection of the drug also decreased the contractility of the heart (dp/dt max); this effect was partly due to the decrease in spotaneous heart rate as shown by comparison with results in electrically paced hearts. No obvious changes of the ECG, limb leads, were recorded except a small increase in PQ and QT which accompanied the much greater increase in PP′ . In cats with acute occlusion of a coronary artery branch, St 567 diminished the elevation of the ST-segment of the epicardial electrogram, parallel with the bradycardic effect. St 567 decreased the heart rate of conscious dogs. The bradycardia achieved thereby was directly correlated with the heart rate before injection of St 567, independent of whether this “control value” was achieved from a spontaneous sinus rate or increased by pretreatment with atropine or hydralazine. The cardiovascular profile of St 567 indicates a decrease in myocardial oxygen demand, a desirable therapeutic measure in the treatment of ischemic heart disease.