Fragasso Gabriele, Piatti Pier Marco, Monti Lucilla, Palloshi Altin, Lu Chunzeng, Valsecchi Gianpietro, Setola Emanuela, Calori Giliola, Pozza Guido, Margonato Alberto, Chierchia Sergio
Dipartimento di Cardiologia e Scienze Cardiovascolari-Unita' di Cardiologia Clinica, Universita' degli Studi di Milano, Istituto Scientifico/Universita' San Raffaele, Milan, Italy.
J Am Coll Cardiol. 2002 Feb 6;39(3):413-9. doi: 10.1016/s0735-1097(01)01768-5.
We sought to assess the effects of heparin and the potential protective effects of trimetazidine (TMZ) on exercise performance, plasma nitric oxide (NO), endothelin-1 (ET-1) and free fatty acid (FFA) release in patients with stable coronary artery disease (CAD).
Heparin has been shown to reduce the ischemic threshold in patients with CAD. Trimetazidine may affect myocardial substrate utilization by shifting energy production from FFA to glucose oxidation.
In four consecutive days, nine patients with CAD each received one of the following four regimens: 1) one tablet of placebo the evening before and at 8 AM and 4 PM on the day of the study, 10 ml of saline in a bolus 10 min before exercise, followed by an infusion of the same preparation; 2) placebo at the same times as in the first regimen, 5,000 IU of heparin 10 min before exercise, followed by 1,000 IU/h; 3) 20 mg TMZ at the same times as in the first regimen, 5,000 IU of heparin 10 min before exercise, followed by 1,000 IU/h; or 4) TMZ at the same times as in the first regimen, 10 ml of saline 10 min before exercise, followed by an infusion of the same preparation.
During placebo (test 2), heparin reduced the time to 1-mm ST-segment depression and prolonged the recovery time, as compared with the results of test 1. When heparin was administered after TMZ (test 3), the time to 1-mm ST-segment depression and the recovery time were similar to those recorded during saline (test 1). Finally, compared with all study phases, TMZ during saline (test 4) prolonged the time to 1 mm. No changes in NO release were found, whereas ET-1 was decreased at peak exercise and during recovery, when the patients were receiving TMZ (tests 3 and 4). Free fatty acids increased after heparin, both with placebo and TMZ.
In patients with CAD, heparin reduces the ischemic threshold. Trimetazidine reduces the effects of heparin, probably by inhibiting FFA oxidation and enhancing glucose metabolism. The concomitant novel observation of reduced ET-1 release is likely to be also dependent on TMZ-induced improvement of endothelial metabolism or reduction of myocardial ischemia.
我们旨在评估肝素以及曲美他嗪（TMZ）对稳定型冠状动脉疾病（CAD）患者运动表现、血浆一氧化氮（NO）、内皮素-1（ET-1）和游离脂肪酸（FFA）释放的影响及潜在保护作用。
已表明肝素可降低CAD患者的缺血阈值。曲美他嗪可能通过将能量产生从FFA转换为葡萄糖氧化来影响心肌底物利用。
连续四天，九名CAD患者每人接受以下四种方案之一：1）研究当天晚上、上午8点和下午4点各服用一片安慰剂，运动前10分钟静脉推注10 ml生理盐水，随后输注相同制剂；2）与第一种方案相同时间服用安慰剂，运动前10分钟注射5000 IU肝素，随后以1000 IU/h输注；3）与第一种方案相同时间服用20 mg TMZ，运动前10分钟注射5000 IU肝素，随后以1000 IU/h输注；或（4）与第一种方案相同时间服用TMZ，运动前10分钟静脉推注10 ml生理盐水，随后输注相同制剂。
在服用安慰剂期间（试验2），与试验1结果相比，肝素缩短了出现1毫米ST段压低的时间并延长了恢复时间。当在TMZ后给予肝素时（试验3），出现1毫米ST段压低的时间和恢复时间与输注生理盐水期间（试验1）记录的相似。最后，与所有研究阶段相比，输注生理盐水期间服用TMZ（试验4）延长了达到1毫米的时间。未发现NO释放有变化，而当患者接受TMZ时（试验3和4），ET-1在运动峰值和恢复期间降低。肝素使用后，无论服用安慰剂还是TMZ，游离脂肪酸均增加。
在CAD患者中，肝素降低缺血阈值。曲美他嗪可能通过抑制FFA氧化和增强葡萄糖代谢来降低肝素的作用。同时观察到ET-1释放减少这一新颖发现可能也依赖于TMZ诱导的内皮代谢改善或心肌缺血减少。
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