Tomai F, Crea F, Gaspardone A, Versaci F, De Paulis R, Penta de Peppo A, Chiariello L, Gioffrè P A
Servizio Speciale di Diagnosi e Cura di Emodinamica, Università di Roma Tor Vergata, European Hospital, Italy.
Circulation. 1994 Aug;90(2):700-5. doi: 10.1161/01.cir.90.2.700.
Brief episodes of ischemia render the heart more resistant to subsequent ischemia; this phenomenon has been called ischemic preconditioning. In some animal species, myocardial preconditioning appears to be due to activation of ATP-sensitive K+ (KATP) channels. The role played by KATP channels in preconditioning in humans remains unknown. The aim of this study was to establish whether glibenclamide, a selective KATP channel blocker, abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations.
Twenty consecutive patients undergoing one-vessel coronary angioplasty were randomized to receive 10 mg oral glibenclamide or placebo. Sixty minutes after glibenclamide or placebo administration, patients were given an infusion of 10% dextrose (8 mL/min) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginning of the infusion, both patient groups underwent coronary angioplasty. The mean values (+/- 1 SD) of ST-segment shifts on the surface 12-lead ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations, both 2 minutes long. In glibenclamide-treated patients, the mean ST-segment shift during the second balloon inflation was similar to that observed during the first inflation (23 +/- 13 versus 20 +/- 8 mm, P = NS), and the severity of cardiac pain was greater (55 +/- 21 versus 43 +/- 23 mm on a scale of 0 to 100, P < .05). Conversely, in placebo-treated patients the mean ST-segment shift during the second inflation was less than that during the first inflation (9 +/- 5 versus 23 +/- 13 mm, P < .001), as was the severity of cardiac pain (15 +/- 15 versus 42 +/- 19 mm, P < .01). Blood glucose levels were significantly reduced 60 minutes after glibenclamide compared with those at baseline (53 +/- 9 versus 102 +/- 10 mg/100 mL, P < .001) in the glibenclamide group; however, before coronary angioplasty, blood glucose levels increased to 95 +/- 19 mg/100 mL, a value similar to that found in placebo group (96 +/- 11 mg/100 mL, P = NS).
In humans, ischemic preconditioning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide, thus suggesting that it is mainly mediated by KATP channels.
短暂的缺血发作可使心脏对随后的缺血更具耐受性；这种现象被称为缺血预处理。在一些动物物种中，心肌预处理似乎是由于ATP敏感性钾离子（KATP）通道的激活。KATP通道在人类预处理中所起的作用尚不清楚。本研究的目的是确定格列本脲（一种选择性KATP通道阻滞剂）是否能消除人类在冠状动脉成形术期间重复球囊扩张后观察到的缺血预处理。
连续20例接受单支冠状动脉成形术的患者被随机分为两组，分别口服10 mg格列本脲或安慰剂。在给予格列本脲或安慰剂60分钟后，患者分别接受10%葡萄糖输注（8 mL/分钟）以纠正血糖水平，或接受相同输注速率的生理盐水输注。输注开始30分钟后，两组患者均接受冠状动脉成形术。在第一次和第二次均持续2分钟的球囊扩张结束时，测量12导联体表心电图和冠状动脉内心电图上ST段移位的平均值（±1 SD）。在接受格列本脲治疗的患者中，第二次球囊扩张期间ST段移位的平均值与第一次扩张期间观察到的相似（23±13对20±8 mm，P =无显著性差异），且胸痛的严重程度更大（在0至100的量表上为55±21对43±23 mm，P <.05）。相反，在接受安慰剂治疗的患者中，第二次扩张期间ST段移位的平均值小于第一次扩张期间（9±5对23±13 mm，P <.001），胸痛的严重程度也是如此（15±15对42±19 mm，P <.01）。与基线相比，格列本脲组在60分钟后血糖水平显著降低（53±9对102±10 mg/100 mL，P <.001）；然而，在冠状动脉成形术前，血糖水平升至95±19 mg/100 mL，与安慰剂组的值相似（96±11 mg/100 mL，P =无显著性差异）。
在人类中，短暂重复冠状动脉闭塞期间的缺血预处理通过格列本脲预处理被完全消除，因此表明其主要由KATP通道介导。
