Silke B, Verma S P, Frais M A, Reynolds G, Taylor S H
Br J Clin Pharmacol. 1986 Dec;22(6):697-706. doi: 10.1111/j.1365-2125.1986.tb02960.x.
The symptomatic benefits of combining beta-adrenoceptor blockers and nitrates in angina pectoris are well recognised. Their actions on cardiac haemodynamics and volumes when combined have been poorly characterized. Accordingly this study investigated a new cardioselective beta-adrenoceptor blocking agent celiprolol and buccal nitroglycerine in 24 patients with angiographically documented coronary artery disease. Following a control period, with confirmed stable haemodynamics, three groups (n = 8/group) of prospectively matched patients, were studied following intravenous celiprolol (8 mg), buccal nitrate (10 mg) or their combination. Haemodynamics and left ventricular ejection fraction (nuclear probe) were determined following each intervention. The actions of each regimen on the haemodynamics of exercise-induced angina were compared by exercise testing in the control state and following each regimen. At rest, celiprolol did not alter haemodynamic parameters. Nitrate therapy reduced left ventricular filling pressure (pulmonary artery occluded pressure--PAOP) and volumes; the ejection fraction and heart rate increased. Combination therapy resulted in a highly significant reduction in left ventricular preload and afterload (PAOP and mean arterial blood pressure) at an increased left ventricular ejection fraction and reduced cardiac volumes; there was a trend to reduce cardiac double product (HR X SBP). During exercise celiprolol reduced systolic blood pressure, heart rate and cardiac index; systemic vascular resistance index increased. Nitrate therapy reduced blood pressure and PAOP, and increased ejection fraction. Combination therapy reduced all components of the triple product (heart rate, systolic blood pressure and PAOP) without affecting the other haemodynamic or radionuclide parameters. These data suggest improvements in cardiac function from the combination of celiprolol and nitrate therapy which were not achieved by either agent when used as monotherapy; they afford an interesting insight into the manner in which such widely utilised therapeutic modalities interact in coronary artery disease.
β-肾上腺素能受体阻滞剂与硝酸盐联合用于治疗心绞痛的症状改善作用已得到充分认可。但它们联合使用时对心脏血流动力学和容量的作用却鲜有描述。因此，本研究对24例经血管造影证实患有冠状动脉疾病的患者，研究了一种新型心脏选择性β-肾上腺素能受体阻滞剂塞利洛尔和口腔硝酸甘油。在确认血流动力学稳定的对照期后，将患者前瞻性地匹配为三组（每组n = 8），分别静脉注射塞利洛尔（8 mg）、口腔给予硝酸盐（10 mg）或两者联合用药后进行研究。每次干预后均测定血流动力学和左心室射血分数（核探头）。通过运动试验在对照状态下以及每种治疗方案后，比较每种治疗方案对运动诱发心绞痛血流动力学的作用。静息时，塞利洛尔不改变血流动力学参数。硝酸盐治疗可降低左心室充盈压（肺动脉闭塞压——PAOP）和容量；射血分数和心率增加。联合治疗导致左心室前负荷和后负荷（PAOP和平均动脉血压）显著降低，同时左心室射血分数增加，心脏容量减少；有降低心脏双乘积（心率×收缩压）的趋势。运动期间，塞利洛尔降低收缩压、心率和心脏指数；全身血管阻力指数增加。硝酸盐治疗降低血压和PAOP，并增加射血分数。联合治疗降低了三联乘积的所有组成部分（心率、收缩压和PAOP），而不影响其他血流动力学或放射性核素参数。这些数据表明，塞利洛尔和硝酸盐联合治疗可改善心脏功能，而单一药物治疗无法达到这一效果；它们为这些广泛应用的治疗方式在冠状动脉疾病中的相互作用方式提供了有趣的见解。
