Venneker E H, Remme W J, van Hoogenhuyze D C, Krauss X H, Bartels G L, Kruijssen D A, Storm C J, van Schelven D
Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
Cardiovasc Drugs Ther. 1994 Apr;8(2):211-9. doi: 10.1007/BF00877329.
Antiischemic effects of beta 1-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial beta 1-agonistic activity, although useful in preserving cardiac function, may counteract such antiischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective beta 1-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10% at 15 minutes and decreased contractility (Vmax) by 7% (both p < .05), whereas cardiac output fell temporarily by 9% (p < .05). Other hemodynamic parameters did not change, except for a significant 11% reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17% lower myocardial oxygen consumption (p < .05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism [lactate extraction 16 +/- 7% vs. -7 +/- 8% (APST I)], less ST depression (21%), and modulation of LV end-diastolic pressure postpacing (all p < .05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional beta 1-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its beta 1-antagonistic profile.
β1受体阻滞剂的抗缺血作用基于其固有的负性肌力和负性变时特性。部分β1激动活性虽然有助于维持心脏功能，但可能通过调节β受体阻滞剂固有的负性心脏效应来抵消这种抗缺血特性。为了研究心脏选择性β1受体拮抗剂兼部分激动剂依帕诺洛尔的急性血流动力学和抗缺血特征，20例左冠状动脉疾病患者在静脉注射4 mg依帕诺洛尔（5分钟内给药）前45分钟（心房起搏应激试验I，APST I）和给药后15分钟（APST II）进行了两次递增性心房起搏试验。在依帕诺洛尔给药后1、3、5、10和15分钟以及基础心率和固定心率时进行了额外测量。依帕诺洛尔立即降低心率，15分钟时最大降低10%，并使收缩性（Vmax）降低7%（两者p < 0.05），而心输出量暂时下降9%（p < 0.05）。除心肌需氧量显著降低11%外，其他血流动力学参数未改变。尽管起搏条件相当，但在APST II期间双乘积和收缩性的降低均显著减少，导致心肌耗氧量降低17%（p < 0.05）。乳酸代谢正常化[乳酸摄取16±7% vs. -7±8%（APST I）]、ST段压低减少（21%）以及起搏后左心室舒张末期压力的调节均表明心肌缺血明显减轻（与APST I相比，所有p < 0.05），而14例患者未出现心绞痛或心绞痛减轻。无一例患者报告有不良反应。因此，在静息状态下，静脉注射依帕诺洛尔可诱导中度、短暂的负性变时和负性肌力作用，但不改变心脏泵功能或血管阻力，这反映了其额外的β1激动特性。另外，在起搏期间，它仍通过负性肌力作用减少缺血并降低心肌需氧量，这反映了其β1拮抗特征。
