Kern M J, Petru M A, Ferry D R, Eilen S D, Barr W K, Porter C B, O'Rourke R A
J Am Coll Cardiol. 1985 Jun;5(6):1438-50. doi: 10.1016/s0735-1097(85)80361-2.
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.
β-肾上腺素能阻滞剂和钙通道阻滞剂单独使用及联合使用时均已被证明对心绞痛治疗有效，它们对冠状动脉血管运动似乎具有相反的作用。先前的研究表明，在冠心病患者的肾上腺素能冷刺激期间，β-肾上腺素能阻滞剂可能会增强冠状动脉收缩，而钙通道阻滞剂则可逆转这种收缩。为评估联合药物治疗的冠状动脉血流动力学效应，在21例患者（9例左前降支冠状动脉狭窄小于50%[A1组]和12例狭窄大于50%[A2组]）中，在静脉注射0.1mg/kg普萘洛尔前后以及舌下含服10mg硝苯地平后，于连续冷加压试验期间测量热稀释法测定的冠状窦和大心脏静脉血流以及平均动脉压。在另外15例患者（6例无左前降支动脉狭窄[B1组]和9例有狭窄[B2组]）中，进行连续冷加压试验并颠倒药物给药顺序。尽管在冷加压试验期间平均动脉压显著升高（p<0.01），但普萘洛尔加硝苯地平后冠状窦阻力反应在任何组中均无统计学意义。然而，有和无左前降支动脉狭窄患者的局部冠状动脉阻力反应有所不同。在A1组中，普萘洛尔加硝苯地平后大心脏静脉阻力未改变。在A2组中，普萘洛尔加硝苯地平后大心脏静脉血流从8±17显著降至-4±12%（与对照组相比p<0.01），大心脏静脉阻力从4±21增加至15±
