The effects of alinidine, an N-allyl derivative of clonidine, on regional myocardial perfusion and performance in the pig with or without atrial pacing

Abstract

The effects of alinidine (0.2–6.0 mg · kg −1), an N-allyl derivative of clodnidine, were investigated on systematic and regional haemodynamics, in particular myocardial perfusion and performance, in the domestic pig, during or in the absence of atrial pacing. The drug had a pronounced bradycardic action and also caused dose-dependent reductions in the maximum rate of rise in left ventricular pressure (max LVdP/dt) cardiac output (CO), arterial blood pressure and in the mean velocity of systolic wall thickening (v̄ SWT) in the absence of atrial pacing. Since the duration of systole was prolonged by alinidine, the total wall thickening during systole (SWT) remained unchanged until the highest dose was given. When the heart rate was kept constant by atrial pacing, there were no changes in the maxLVdP/dt, CO or v̄ SWT with lower doses (< 0.4 mg · kg −1) of alinidine. With higher doses, however, there was a significant reduction in these variables, demonstrating a clear negative inotropic action of the drug. The drecrease in CO was entirely at the expense of its nutrient fraction (NCO), since systematic arteriovenous anastomotoc flow remained unchanged. However, the reduction in NCO did not hamper tissue oxygenation either because of autoregulation within blood vessels (cerebral and renal), or because the tissues were able to extract more O 2 from the blood. Similarly, despite the reduction of myocardial perfusion, no imbalance in the myocardial oxygen supply-demand relationship was noticed due to a simultaneous reduction of th myocardial work in both unpaced and paced hearts. Morevoer, the changes in the intramyocardial blood flow were quite uniform. It is concluded that alinidine has a negative chronotropic and, in higher doses, a negative inotropic action. The cardiovascular profile of the drug suggests that it could be useful in patients with ischaemic heart disease.