Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries

Although adrenergic activation plays a major role in the initiation of experimental myocardial ischemia, the significance of alpha-adrenergic coronary constriction in humans has been questioned. The present study assessed the impact of selective alpha-adrenergic receptor activation in patients with normal or atherosclerotic coronary arteries.

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 alpha1-agonist methoxamine (M) were injected. Identical doses of the alpha2-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 (39.0+/-9.4 versus 15.2+/-7.0). In groups 3 and 4, CBF was also decreased dose-dependently, with a maximum at 10 mg B (63.3+/-24.8 versus 49. 1+/-27.9 and 41.5+/-19.0 versus 12.7+/-8.0, respectively). In group 5, there was more net lactate production with B than with M (-0. 34+/-0.11 versus -0.04+/-0.09 mmol/L).

In normal coronary arteries, alpha1-adrenergic activation does not reduce CBF, whereas alpha2-adrenergic activation reduces CBF by microvascular constriction. Both alpha1- and alpha2-adrenergic epicardial and microvascular constriction are augmented by atherosclerosis and can induce myocardial ischemia.