Author + information
- Received July 16, 1984
- Revision received October 8, 1984
- Accepted November 4, 1984
- Published online April 1, 1985.
- Morton J. Kern, MD, FACC*,1,
- John D. Horowitz, MD1,2,
- Peter Ganz, MD1,4,
- Jorge Gaspar, MD1,3,
- Wilson S. Colucci, MD1,5,
- Beverly H. Lorell, MD, FACC1,5,
- William H. Barry, MD, FACC1 and
- Gilbert H. Mudge Jr., MD1
- ↵*Address for reprints: Morton J. Kern, MD, Department of Medicine/Cardiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284.
Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phen-tolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 ± 5 beats/min (± 1SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 ± 4% (102 ± 14 to 111 ± 14 mm Hg, p < 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 ± 19% (1.02 ± 0.46 to 1.15 ± 0.57 units, p < 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 ± 5% (p < 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 ± 11%, p = NS), which was significantly less than before trimazosin (p < 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha1-receptor blockade.
These data suggest that although the hypertensive response to cold pressor testing is somewhat blunted by selective alpha1,-adrenoceptor blockade, the reflex coronary vasoconstriction during adrenergic stimulation in some patients with coronary artery disease can be significantly attenuated. Use of agents that block alpha2-adrenoceptors has been clinically unsatisfactory because of the adverse myocardial effects of increased norepinephrine release. Selective alpha1-receptor blockade may have an additional advantage over nonselective alpha-adrenergic blockade in that the release of norepinephrine is also attenuated, thus potentially producing less augmentation of heart rate and myocardial oxygen demand.
- Received July 16, 1984.
- Revision received October 8, 1984.
- Accepted November 4, 1984.
- American College of Cardiology Foundation