Regional coronary vasoconstriction after combined beta-adrenergic and calcium channel blockade in patients with coronary artery disease

Abstract

The beta-adrenergic and calcium channel blocking drugs, which individually and combined have proven efficacious in the treatment of angina pectoris, appear to have opposing effects on coronary artery vasomotion. Previous studies have shown that beta-adrenergic blockade may potentiate and calcium channel blockade reverse coronary vasoconstriction during adrenergic cold stimulation in patients with coronary artery disease. To assess the coronary hemodynamic effects of combined drug therapy, thermodilution coronary sinus and great cardiac vein flow and mean arterial pressure were measured during serial cold pressor testing, both before and after 0.1 mg/kg of intravenous propranolol and again after the addition of 10 mg of sublingual nifedipine in 21 patients (9 without [group A1] and 12 with [group A2] greater than 50% narrowing of the left anterior descending coronary artery). In an additional 15 patients (6 patients without [group B1] and 9 with [group B2] left anterior descending artery stenosis), serial cold pressor testing was performed reversing the drug order. Despite significant increases in mean arterial pressure (p less than 0.01) during cold pressor testing, coronary sinus resistance responses after propranolol plus nifedipine were not statistically significant for any group. However, regional coronary resistance responses differed between patients with and without left anterior descending artery stenosis. In group A1, great cardiac vein resistance was unchanged after propranolol plus nifedipine. In group A2, great cardiac vein flow decreased significantly after propranolol plus nifedipine from 8 +/- 17 to -4 +/- 12% (p less than 0.01 versus control), and great cardiac vein resistance increased from 4 +/- 21 to 15 +/- 19% (p less than 0.01 versus control). A similar significant response was observed for groups B1 and B2. Regional coronary vasoconstriction during adrenergic stimulation after combined drug therapy was only observed in patients with significant left anterior descending artery stenosis. These data suggest that in some patients with severe coronary artery disease, combined beta-adrenergic and calcium channel blockade modified regional coronary responses to adrenergic stimulation with an inhomogeneous distribution of blood flow to potentially ischemic regions without affecting total coronary blood flow. These data also imply that an improvement in anginal symptoms after combined drug therapy may be due primarily to mechanisms that reduce myocardial oxygen demand rather than to improved myocardial oxygen supply.

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.…”

Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications.

“…Propranolol augments the coronary vasoconstrictive response elicited in coronary patients by the cold pressor test.8 9 Theoretically, diltiazem might be expected to be a better antianginal drug in a cold environment because it is a coronary vasodilator, in contrast to propranolol. In this study, both propranolol and diltiazem delayed the onset of ischemia during exercise at both -8°and 200 C. This beneficial effect at normal temperatures is quantitatively similar to results of previous studies.17 The antianginal efficacy of these drugs has not been investigated at low temperatures.…”

“…,B-Adrenergic-blocking drugs potentiate the coronary vasoconstriction induced at the site of atherosclerotic lesions by the cold pressor test.8 9 In contrast, nifedipine blocks this response. 10 The efficacy of antianginal drugs has not been assessed in a cold environment.…”

Combined use of beta-blockers and non-dihydropyridine calcium channel blockers: possible or contraindicated?

“…При этом есть и противоположные патофизиологические аспекты такого взаимодействия. Например, БКК противодействуют коронарной вазоконстрикции, вследствие применения БАБ, что может увеличить перфузию только в неишемизированных областях и может уменьшить кровоток в зонах ишемии [4,5]. Увеличение риска ишемии миокарда и ухудшение течения стенокардии при применении такой комбинации также возможно вследствие потенцирования гипотензивного действия [6], увеличения нагрузки на стенку левого желудочка (ЛЖ) или выраженной брадикардии [7,8].…”