Anion-channel blockade with alinidine: A specific bradycardic drug for coronary heart disease without negative inotropic activity?

Abstract

In 14 patients undergoing cardiac catheterization for suspected coronary artery disease, alinidine, 0.6 mg/kg, was administered intravenously to determine its effects on left ventricular (LV) function, coronary blood flow and myocardial oxygen consumption. To assess effects independent of changes in heart rate (HR), measurements were made at spontaneous and matched pacing HRs. At spontaneous HR, alinidine decreased HR from 70 ± 2 to 61 ± 3 beats/min (p < 10 −6). Peak rate of LV pressure decreased from 1,652 ± 92 to 1,371 ± 80 mm Hg/s (p < 10 −5) and Vmax decreased from 47 ± 3 to 41 ± 2 s −1 (p < 10 −4). Coronary sinus blood flow decreased from 109 ± 9 to 89 ± 7 ml/min (p < 0.01) and myocardial oxygen consumption from 10.9 ± 1.0 to 9.0 ± 0.8 ml O 2/min (p < 0.05). At a matched pacing HR of 98 ± 3 beats/min before and after alinidine administration, peak rate of LV pressure decreased from 1,984 ± 124 to 1,793 ± 106 mm Hg/s (p < 10 −4) and Vmax from 60 ± 5 to 56 ± 4 s −1 (p < 0.02). Coronary sinus blood flow and myocardial oxygen consumption were not significantly changed at matched pacing HRs. The time constant of the first 40 ms of LV isovolumic relaxation was prolonged by alinidine only during spontaneous HR. Thus, alinidine results in a bradycardia-dependent decrease in myocardial oxygen consumption. It has negative inotropic properties independent of changes in HR and so is not a pure bradycardia-specific agent.