Lawton J S, Hsia P W, Allen C T, Damiano R J
Department of Surgery, Medical College of Virginia, Richmond, USA.
J Thorac Cardiovasc Surg. 1997 Mar;113(3):567-75. doi: 10.1016/S0022-5223(97)70372-6.
The superiority of hyperpolarized arrest with adenosine triphosphate-sensitive potassium channel openers over standard hyperkalemic depolarizing cardioplegia during normothermic ischemia has been documented. This study examined the hypothesis that pinacidil would provide superior protection in a more clinically relevant model of an acutely injured heart and hypothermic cardioplegic arrest.
In a blood-perfused, parabiotic, rabbit heart Langendorff model, hearts underwent 15 minutes of unprotected global normothermic ischemia before the administration of 50 ml of cardioplegic solution at 4 degrees C, followed by 50 minutes of hypothermic (15 degrees C) ischemia and 30 minutes of reperfusion. The cardioplegic solutions administered consisted of Krebs-Henseleit solution alone (N = 6), Krebs-Henseleit solution with pinacidil (50 mumol/L; N = 10), Krebs-Henseleit solution with pinacidil (50 mumol/L) and glibenclamide (a potassium channel blocker, 10 mumol/L; N = 8), or St. Thomas' Hospital solution (N = 8). The percent recovery of developed pressure, linear diastolic pressure-volume relationships, and coronary blood flow were compared.
The percent recovery of developed pressure was 32.8% +/- 2.8%, 43.0% +/- 4.3%, 46.5% +/- 2.2%, and 49.3% +/- 2.7% for the Krebs-Henseleit, the Krebs-Henseleit with pinacidil and glibenclamide, the St. Thomas' Hospital, and the Krebs-Henseleit with pinacidil groups, respectively. No hearts had ventricular fibrillation on reperfusion.
During hypothermic hyperpolarized arrest, as opposed to normothermic ischemia as in our previous studies, there was neither an increased incidence of ventricular fibrillation nor prolonged electrical activity when compared with results during traditional hyperkalemic arrest. Myocardial protection by St. Thomas' Hospital solution and pinacidil was superior (p = 0.009) to that with Krebs-Henseleit solution alone. The protection provided by pinacidil was lost with the addition of glibenclamide, indicating that the drug has adenosine triphosphate-sensitive potassium channel activity during hypothermia.
已证实，在常温缺血期间，三磷酸腺苷敏感性钾通道开放剂诱导的超极化停搏优于标准的高钾去极化心脏停搏。本研究检验了吡那地尔在急性损伤心脏和低温心脏停搏的更具临床相关性模型中能提供更好保护的假设。
在一个血液灌注的、联体的兔心脏Langendorff模型中，心脏在给予50毫升4℃心脏停搏液之前经历15分钟无保护的全心常温缺血，随后是50分钟低温（15℃）缺血和30分钟再灌注。给予的心脏停搏液包括单纯的克雷布斯-亨泽莱特溶液（N = 6）、含吡那地尔（50微摩尔/升）的克雷布斯-亨泽莱特溶液（N = 10）、含吡那地尔（50微摩尔/升）和格列本脲（一种钾通道阻滞剂，10微摩尔/升）的克雷布斯-亨泽莱特溶液（N = 8）或圣托马斯医院溶液（N = 8）。比较了左心室发展压恢复百分比、线性舒张期压力-容积关系和冠状动脉血流量。
克雷布斯-亨泽莱特组、含吡那地尔和格列本脲的克雷布斯-亨泽莱特组、圣托马斯医院溶液组和含吡那地尔的克雷布斯-亨泽莱特组的左心室发展压恢复百分比分别为32.8%±2.8%、43.0%±4.3%、46.5%±2.2%和49.3%±2.7%。再灌注时无心室颤动发生。
与我们之前研究中的常温缺血不同，在低温超极化停搏期间，与传统高钾停搏时的结果相比，心室颤动发生率没有增加，电活动也没有延长。圣托马斯医院溶液和吡那地尔的心肌保护作用优于单纯的克雷布斯-亨泽莱特溶液（p = 0.009）。加入格列本脲后，吡那地尔提供的保护作用丧失，表明该药物在低温期间具有三磷酸腺苷敏感性钾通道活性。
