Spivey W H, Lathers C M
Ann Emerg Med. 1985 Oct;14(10):939-44. doi: 10.1016/s0196-0644(85)80233-x.
Clinical studies have shown that treatment with chronic timolol after a myocardial infarction decreases the incidence of reinfarction and mortality. It also limits the size of infarction when it is given IV during the acute phase of an infarction and followed by chronic oral dosing. It has been postulated that beta blockers work not only by a direct mechanism on the heart, but by altering neural discharge to the heart and depressing the sympathetic overactivity seen in 35% of patients immediately after an infarction. Our study examined the effect of timolol on sympathetic cardiac neural discharge, blood pressure, heart rate, and rhythm during acute coronary occlusion produced by ligation of the left anterior descending artery 10 to 14 mm below its origin in alpha-chloralose-anesthetized cats. Timolol or normal saline 5 mg/kg IV was given five minutes post coronary occlusion. The infusion of timolol significantly decreased the mean arterial blood pressure and heart rate. Sympathetic cardiac neural discharge in the group treated with timolol five minutes post coronary occlusion did not differ from that in the saline group. Thus there was a nonuniform (an increase, a decrease, or no change) sympathetic cardiac neural discharge associated with the production of occlusion-induced arrhythmia. These data suggest that the action of timolol on the sympathetic cardiac neural discharge is not its major mode of protection.
临床研究表明，心肌梗死后长期使用噻吗洛尔进行治疗可降低再梗死发生率和死亡率。在梗死急性期静脉注射噻吗洛尔并随后进行长期口服给药时，它还能限制梗死面积。据推测，β受体阻滞剂不仅通过对心脏的直接作用机制发挥作用，还通过改变传入心脏的神经冲动并抑制在35%的患者梗死发作后立即出现的交感神经过度活动来发挥作用。我们的研究在α-氯醛糖麻醉的猫身上，通过在左冠状动脉前降支起始部下方10至14毫米处进行结扎，造成急性冠状动脉闭塞，在此期间研究了噻吗洛尔对交感心脏神经冲动、血压、心率及心律的影响。冠状动脉闭塞5分钟后静脉注射5毫克/千克的噻吗洛尔或生理盐水。噻吗洛尔输注显著降低了平均动脉血压和心率。冠状动脉闭塞5分钟后接受噻吗洛尔治疗的组中，交感心脏神经冲动与生理盐水组并无差异。因此，与闭塞性心律失常的发生相关的交感心脏神经冲动并不一致（增加、减少或无变化）。这些数据表明，噻吗洛尔对交感心脏神经冲动的作用并非其主要的保护模式。
