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Anion-channel blockade with alinidine: a specific bradycardic drug for coronary heart disease without negative
Insights
Alinidine reduces heart rate, decreasing myocardial oxygen consumption in a bradycardia-dependent manner. However, it also exhibits negative inotropic effects independent of heart rate changes.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Physiology
Background:
- Coronary artery disease necessitates understanding drugs affecting cardiac function.
- Alinidine's impact on left ventricular (LV) function, coronary blood flow, and myocardial oxygen consumption requires detailed investigation.
Purpose of the Study:
- To evaluate the effects of intravenously administered alinidine (0.6 mg/kg) on LV function, coronary blood flow, and myocardial oxygen consumption.
- To differentiate alinidine's effects at spontaneous versus matched heart rates (HR) to isolate bradycardia-specific actions.
Main Methods:
- Cardiac catheterization was performed in 14 patients with suspected coronary artery disease.
- Measurements of LV pressure, coronary sinus blood flow, and myocardial oxygen consumption were taken at spontaneous and paced HRs before and after alinidine administration.
Main Results:
- Alinidine significantly decreased HR, peak LV pressure rate, Vmax, coronary sinus blood flow, and myocardial oxygen consumption at spontaneous HR.
- At matched pacing HR, alinidine still reduced peak LV pressure rate and Vmax but did not significantly alter coronary blood flow or oxygen consumption.
- The time constant of LV isovolumic relaxation was prolonged by alinidine only at spontaneous HR.
Conclusions:
- Alinidine induces a bradycardia-dependent reduction in myocardial oxygen consumption.
- The drug possesses negative inotropic properties independent of HR changes, indicating it is not solely a bradycardia-specific agent.
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 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.