Van Den Heuvel A F, van der Ent M, van Veldhuisen D J, Kruijssen D A, Bartels G L, Remme W J
Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
J Cardiovasc Pharmacol. 1998 Apr;31(4):506-12. doi: 10.1097/00005344-199804000-00006.
Recently, different beta-blockers have been shown to be effective in the treatment of chronic heart failure (CHF), but the importance of their ancillary properties is not clear. Epanolol is a selective beta1-blocker with intrinsic sympathomimetic activity, which has been shown useful in angina pectoris, but its value in patients with left ventricular (LV) dysfunction and CHF is unknown. We examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of invasive hemodynamics and neurohormones was performed at rest and during myocardial ischemia, which was induced by atrial pacing. All measurements were performed before and after epanolol. Before epanolol, pacing-induced ischemia led to a similar increase in norepinephrine and coronary sinus blood flow in both groups. After epanolol, the increase in neurohormones was more pronounced in the group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar effect was observed for angiotensin II. Further, in the LV-dysfunction group, coronary sinus blood flow increased less, and coronary vascular resistance decreased less (both values, p < 0.05). Despite the fact that the increase in double product was decreased to a similar extent in both groups, ischemia was reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction, neurohumoral activation after epanolol may impair adequate coronary flow response, and this may limit its antiischemic properties. Because of the small size of the study, no definitive inference on the clinical benefit of epanolol in patients with ischemic LV function can be made from this study.
最近,不同的β受体阻滞剂已被证明在治疗慢性心力衰竭(CHF)方面有效,但其辅助特性的重要性尚不清楚。依泮洛尔是一种具有内在拟交感活性的选择性β1受体阻滞剂,已被证明对心绞痛有效,但其在左心室(LV)功能不全和CHF患者中的价值尚不清楚。我们研究了依泮洛尔对LV功能不全患者(n = 8;平均LV射血分数,0.33±0.08)的影响,并将其与LV功能正常的患者(n = 8;平均LV射血分数,0.52±0.04)进行比较。在静息状态和心房起搏诱发的心肌缺血期间进行有创血流动力学和神经激素测量。所有测量均在依泮洛尔给药前后进行。在给予依泮洛尔之前,起搏诱发的缺血导致两组去甲肾上腺素和冠状窦血流量的相似增加。给予依泮洛尔后,LV功能不全组神经激素的增加更为明显(LV功能不全患者去甲肾上腺素为1130±164 pg/ml,正常受试者为637±41 pg/ml;p < 0.05)。血管紧张素II也观察到类似的效果。此外,在LV功能不全组中,冠状窦血流量增加较少,冠状血管阻力降低较少(两者p值均< 0.05)。尽管两组双乘积的增加程度相似降低,但仅在LV功能正常时缺血减轻(p < 0.05)。在缺血性LV功能不全中,依泮洛尔后的神经体液激活可能会损害充分的冠状动脉血流反应,这可能会限制其抗缺血特性。由于研究规模较小,无法从本研究中对依泮洛尔在缺血性LV功能患者中的临床益处做出明确推断。