Background-Although adrenergic activation plays a major role in the initiat
ion of experimental myocardial ischemia, the significance of alpha-adrenerg
ic coronary constriction in humans has been questioned. The present study a
ssessed the impact of selective alpha-adrenergic receptor activation in pat
ients with normal or atherosclerotic coronary arteries.
Methods and Results-In 39 patients, coronary blood flow (CBF, mL/min) was d
etermined 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 alpha(1)-agonis
t methoxamine(M) were injected. Identical doses of the alpha(2)-agonist BHT
933 (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-d
ependently, with a maximum at 10 mg B (63.3+/-24.8 versus 49.1+/-27.9 and 4
1.5+/-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 mm
ol/L).
Conclusions-In normal coronary arteries, alpha(1)-adrenergic activation doe
s not reduce CBF, whereas alpha(2)-adrenergic activation reduces CBF by mic
rovascular constriction Both alpha(1)- and alpha(2)-adrenergic epicardial a
nd microvascular constriction are augmented by atherosclerosis and can indu
ce myocardial Ischemia.