Tagliamonte Ercole, Rigo Fausto, Cirillo Teresa, Astarita Costantino, Quaranta Gaetano, Marinelli Umberto, Caruso Archimede, Romano Carlo, Capuano Nicola
Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, Italy.
Echocardiography. 2015 Mar;32(3):516-21. doi: 10.1111/echo.12674. Epub 2014 Jul 4.
Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient.
Fifty-eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double-blind, placebo-controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8-week therapy.
CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups.
Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.
雷诺嗪通过抑制晚钠电流减少钠依赖性钙超载，改善心肌缺血期间的舒张期张力和氧代谢。在患有心绞痛、有心肌缺血证据但无阻塞性冠状动脉疾病（CAD）的患者中，异常的冠状动脉自动调节起关键作用。经胸多普勒衍生的冠状动脉血流储备（CFR）是冠状动脉反应性的指标，在微血管功能障碍和冠状动脉狭窄时均降低。本研究的目的是评估雷诺嗪对该组患者CFR的影响。
58例（39例男性，19例女性）患有心绞痛且有心肌缺血证据但无阻塞性CAD的患者参加了一项双盲、安慰剂对照试验。参与者被分配接受雷诺嗪（29例）或安慰剂（29例）治疗8周（每日两次，剂量可达500毫克）。CFR被确定为静脉注射双嘧达莫诱导的充血期与舒张期冠状动脉血流速度基线的比值。在8周治疗前后评估CFR。
所有患者均成功完成CFR测定。雷诺嗪组和安慰剂组在基线特征和CFR方面无显著差异。8周后，雷诺嗪组CFR显著增加（2.54±0.44对1.91±0.31；P = 0.005），而安慰剂组未增加（1.99±0.32对1.94±0.29；P =无统计学意义）。在8周治疗期间无患者退出。两组副作用相似。
雷诺嗪能够改善这些患者的CFR。这可能是由于异常冠状动脉自动调节得到改善，既降低了舒张期冠状动脉血流速度基线，又增加了充血期舒张期冠状动脉血流速度。
