Anion-channel blockade with alinidine: a specific bradycardic drug for coronary heart disease without negative inotropic activity?
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 less than 10(-6]. Peak rate of LV pressure decreased from 1,652 +/- 92 to 1,371 +/- 80 mm Hg/s (p less than 10(-5] and Vmax decreased from 47 +/- 3 to 41 +/- 2 s-1 (p less than 10(-4]. Coronary sinus blood flow decreased from 109 +/- 9 to 89 +/- 7 ml/min (p less than 0.01) and myocardial oxygen consumption from 10.9 +/- 1.0 to 9.0 +/- 0.8 ml O2/min (p less than 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 less than 10(-4] and Vmax from 60 +/- 5 to 56 +/- 4 s-1 (p less than 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.
D000328:Adult; D000368:Aged; D001919:Bradycardia / Q000188:drug therapy / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial / Q000379:methods; D002316:Cardiotonic Agents / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*
D002316:Cardiotonic Agents; C022192:alinidine; D003000:Clonidine