Klepzig H, Kober G, Matter C, Luus H, Schneider H, Boedeker K H, Kiowski W, Amann F W, Gruber D, Harris S, Burger W
Department of Medicine, J. W. Goethe University Frankfurt /Main, Germany.
Eur Heart J. 1999 Mar;20(6):439-46. doi: 10.1053/euhj.1998.1242.
Glimepiride is a new sulfonylurea for diabetes treatment which is supposed to impact less on extra-pancreatic ATP-dependent K+ channels than the conventional drug glibenclamide. This study was performed to evaluate whether this results in a better maintenance of ATP-dependent K+ channel mediated ischaemic myocardial preconditioning.
In a double-blind placebo-controlled study the period of total coronary occlusion during balloon angioplasty of high grade coronary artery stenoses was used as a model to compare the effects of both drugs. Quantification of myocardial ischaemia was achieved by recording the intracoronary ECG and the time to the occurrence of angina during vessel occlusion. All patients underwent three dilatations. The first dilatation (dilatation 1) served to determine the severity of ischaemia during vessel occlusion. During dilatation 2, baseline values were recorded. Thereafter, glimepiride (15 patients: 1.162 mg), glibenclamide (15 patients: 2.54 mg) or placebo (15 patients) were intravenously administered over 12 min. Dilatation 3 started 10 min after the beginning of the drug administration. Mean ST segment shifts in the placebo group decreased by 35% (dilatation 2: 0.23; dilatation 3:0.15 mV; CI -0.55 to 0.00 mV; P=0.049). A similar reduction also occurred in the glimepiride group, in which repetitive balloon occlusion led to a 34% reduction (dilatation 2: 0.35; dilatation 3: 0.23 mV; CI -0.21 to -0.02 mV; P=0.01). There was little influence however, on mean ST segment shifts in the glibenclamide group (dilatation 2 and dilatation 3: 0.24 mV; CI -0.10 to 0.25 mV; P=0.34). Accordingly, time to angina during balloon occlusion slightly increased (by 30%) in the placebo group (dilatation 2: 37 s; dilatation 3: 48 s; CI 0.0 to 15.0 s; P=0.16); increased by 13% in the glimepiride group (dilatation 2: 40 s; dilatation 3: 45 s; CI 0.0 to 14.0 s; P=0023); and remained unchanged in the glibenclamide group (dilatation 2 and dilatation 3: 30 s; CI -7.5 to 7.5 s; P=0.67).
These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it.
格列美脲是一种用于治疗糖尿病的新型磺酰脲类药物，与传统药物格列本脲相比，它对胰腺外ATP依赖性钾通道的影响较小。本研究旨在评估这是否能更好地维持ATP依赖性钾通道介导的缺血性心肌预处理。
在一项双盲安慰剂对照研究中，将冠状动脉严重狭窄球囊血管成形术期间的总冠状动脉闭塞时间用作模型，以比较两种药物的效果。通过记录冠状动脉内心电图和血管闭塞期间心绞痛发作时间来量化心肌缺血。所有患者均接受三次扩张。第一次扩张（扩张1）用于确定血管闭塞期间的缺血严重程度。在扩张2期间，记录基线值。此后，在12分钟内静脉注射格列美脲（15例患者：1.162毫克）、格列本脲（15例患者：2.54毫克）或安慰剂（15例患者）。在药物给药开始10分钟后开始扩张3。安慰剂组的平均ST段移位下降了35%（扩张2：0.23；扩张3：0.15毫伏；可信区间-0.55至0.00毫伏；P=0.049）。格列美脲组也出现了类似的降低，其中重复性球囊闭塞导致降低了34%（扩张2：0.35；扩张3：0.23毫伏；可信区间-0.21至-0.02毫伏；P=0.01）。然而，格列本脲组对平均ST段移位影响很小（扩张2和扩张3：0.24毫伏；可信区间-0.10至0.25毫伏；P=0.34）。相应地，球囊闭塞期间心绞痛发作时间在安慰剂组略有增加（30%）（扩张2：37秒；扩张3：48秒；可信区间0.0至15.0秒；P=0.16）；在格列美脲组增加了13%（扩张2：40秒；扩张3：45秒；可信区间0.0至14.0秒；P=0.023）；在格列本脲组保持不变（扩张2和扩张3：30秒；可信区间-7.5至7.5秒；P=0.67）。
这些结果表明，格列美脲可维持心肌预处理，而格列本脲可能会抑制心肌预处理。
