Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease.

Abstract

SUMMARY Although ,t-adrenergic blocking agents reduce myocardial oxygen consumption and symptoms of myocardial ischemia in patients with coronary artery disease (CAD), propranolol has been reported to exacerbate coronary artery spasm in some patients with variant angina. To determine whether increased coronary vasomotor tone can be induced by 3-adrenergic blockade, we measured the changes in coronary vascular resistance (CVR) during cold pressor testing (CPT) in 15 patients, nine with severe CAD and six with normal left coronary anatomy, before and after i.v. propranolol (0.1 mg/kg). Coronary blood flow was measured by coronary sinus thermodilution. CVR was calculated as mean arterial pressure divided by coronary sinus blood flow. Heart rate was maintained constant at a paced subanginal rate of 95 + 5 beats/min.Before propranolol, CPT induced significant increases in coronary vascular resistance in patients with CAD (15.0 ± 2.2%, p < 0.02), but no increase in CVR in the normal patients. After propranolol, the CVR change during CPT was augmented for patients with CAD (29 ± 6%, p < 0.01) and for the normal population (9 ± 5%, NS). The potentiated increase in CVR occurred without significant changes in resting CVR or in the magnitude of the hypertensive response to CPT.We conclude that ,B-adrenergic blockade with propranolol can potentiate coronary artery vasoconstriction in some patients with CAD, possibly mediated by unopposed ct-adrenergic vasomotor tone. These changes may be important in patients in whom intense adrenergic stimulation may increase coronary artery tone and adversely influence the balance between myocardial oxygen supply and demand.COMPELLING EVIDENCE suggests that myocardial ischemia may be induced by a reduction in myocardial oxygen supply due to coronary artery spasm. Primary decreases in coronary blood flow associated with abnormal coronary vasomotor reactivity have been found to occur not only in variant angina, I but also in classic and unstable angina,2 3 cold-induced angina,4 exercise-induced angina5 6 and myocardial infarction.7 8 The mechanism of such variation in coronary artery vasomotion is unknown, but several studies have implicated a central role for the adrenergic nervous system. ProtocolThe investigational protocol and consent form were approved by the Human Subjects Committee of the Brigham and Women's Hospital. After the patients gave informed consent, treatment with 3-adrenergic blocking agents was withheld for at least 12-24 hours before cardiac catheterization, and long-acting nitrate preparations were withheld for at least 6 hours before catheterization. Before coronary arteriography, all patients received 0.4 mg of sublingual nitroglycerin and six also received 0.5 mg of i.v. atropine.Fifteen minutes after completion of the diagnostic cardiac catheterization and coronary angiography, a #8F coronary sinus thermodilution pacing catheter (Wilton Webster Laboratories) was inserted into an antecubital vein and advanced under fluoroscopic guidance to the coronary sinus. The lo...

Role of β 2 Adrenergic Receptors in Human Atherosclerotic Coronary Arteries

“…Previous data from Kern et al 22,23 have suggested that ␤-blockers (intravenous propranolol) could potentiate coronary vasoconstriction in patients with coronary artery disease undergoing a cold pressor test because of an unopposed ␣-adrenergic vasomotor tone. On the contrary, Gaglione et al 24 showed a significant vasodilation of stenotic coronary arteries after intracoronary propranolol in patients undergoing supine bicycle stress testing.…”

Norepinephrine Elicits β 2 -Receptor–Mediated Dilation of Isolated Human Coronary Arterioles

“…17,29 Previous studies have already documented that ␤-adrenergic blockade can potentiate coronary artery constriction in patients with coronary artery disease, which is most likely mediated by unopposed ␣-adrenergic vasomotor tone. 33 In addition, it has been shown that adrenergically mediated coronary vascular tone may contribute to ischemia in patients with coronary disease. 34 Responses of coronary arterioles and small arteries to NE have been investigated by many studies in vivo and in vitro, revealing that adrenoceptors are located on several cell types and tissues, including endothelium, 4,17-28 smooth muscle, 26 -28 …”

Cocaine and the Heart

“…There is the concern that β-blockers would impede β-adrenergic mediated vasodilation.There have been reports of β-blocker associated decrease in coronary blood flow, increased seizure activity, and possible increased mortality. 36,37 However, β-blockade may be beneficial against the pathophysiologic effects of cocaine in the peri-MI period, including systolic dysfunction heart failure, coronary artery thrombotic occlusion, and ventricular arrhythmias. A recent retrospective cohort study concluded that the administration of β-blockers after the acute event was associated with a reduction in the incidence of MI after cocaine use and that the benefit of β-blockers on myocardial function may offset the risk of coronary artery vasospasm.…”