tInfluence of Acute α1Adrenergic Antagonism on Heart Rate Variability in Patients with Old Myocardial Infarction

Decreased heart rate (HR) variation is a predictor of cardiac and arrhythmic death after myocardial infarction (MI). The present study examined the influence of alpha-adrenergic system on HR variation (HRV). A novel alpha 1-adrenergic antagonist, abanoquil (UK 52,046) was administered acutely to 27 patients with old MI in random placebo-controlled cross-over design. Abanoquil decreased mean sinus interval for 24 h from 884 +/- 119 (mean +/- SD) to 830 +/- 116 ms (p = 0.0001). The total spectral (0.01-1.0 Hz) amplitude in HRV decreased from 44.6 +/- 14.8 to 40.6 +/- 14.8 ms (p = 0.018). Corresponding decreases were from 28.3 +/- 10.6 to 25.3 +/- 10.8 ms (p = 0.011) in the low-frequency band (0.04-0.15 Hz) and from 13.8 +/- 6.6 to 12.1 +/- 6.1 ms (p = 0.055) in the high-frequency band (0.15-0.40 Hz). Changes of similar magnitude were observed during active and sleep time. All changes in HRV were related by covariate analysis to the decrease in sinus interval and were not associated with an orthostatic decrease in blood pressure (BP) induced by abanoquil. The dominant effect of acute alpha 1-adrenergic antagonism appears to be a decrease in parasympathetic activity, although it may also stabilize sympathetic control of the heart. Thus, the autonomic nervous modification caused by alpha-adrenoceptor antagonists might be disadvantageous in treatment of patients at high risk of fatal cardiac events.