Augmented a-Adrenergic Constriction of Atherosclerotic Human Coronary Arteries

Background—Although adrenergic activation plays a major role in the initiation of experimental myocardial ischemia, the significance of a-adrenergic coronary constriction in humans has been questioned. The present study assessed the impact of selective a-adrenergic receptor activation in patients with normal or atherosclerotic coronary arteries. Methods and Results—In 39 patients, coronary blood flow (CBF, mL/min) was determined from combined angiography and Doppler measurements. In 8 patients with normal coronary arteries (group 1) and 9 with single coronary artery stenosis (group 2), doses of 1, 2.5, 5, and 10 mg IC of the a1-agonist methoxamine (M) were injected. Identical doses of the a2-agonist BHT933 (B) were injected in 8 patients with normal coronary arteries (group 3) and 8 with single stenosis (group 4). In 6 additional patients with single stenosis (group 5), aortocoronary sinus lactate differences were measured in response to M and B. CBF remained unchanged in group 1. In contrast, CBF was decreased dose-dependently in group 2, with a maximum at 10 mg M (39.069.4 versus 15.267.0). In groups 3 and 4, CBF was also decreased dose-dependently, with a maximum at 10 mg B (63.3624.8 versus 49.1627.9 and 41.5619.0 versus 12.768.0, respectively). In group 5, there was more net lactate production with B than with M (20.3460.11 versus 20.0460.09 mmol/L). Conclusions—In normal coronary arteries, a1-adrenergic activation does not reduce CBF, whereas a2-adrenergic activation reduces CBF by microvascular constriction. Both a1and a2-adrenergic epicardial and microvascular constriction are augmented by atherosclerosis and can induce myocardial ischemia. (Circulation. 1999;99:2090-2097.)