Jayawant A M, Damiano R J
Department of Surgery, Medical College of Virginia, Richmond, USA.
Ann Thorac Surg. 1998 Oct;66(4):1329-35; discussion 1335-6. doi: 10.1016/s0003-4975(98)00772-3.
Our laboratory has shown that the potassium-channel opener pinacidil is an effective cardioplegic agent. A theoretical benefit of cardioplegia with potassium-channel openers is that it arrests the heart at hyperpolarized membrane potentials, a state of minimal metabolic requirement. This study was designed to examine another nondepolarizing agent, adenosine, and to test the hypothesis that it could provide comparable cardioprotection or augment potassium-channel opener cardioplegia.
Using the blood-perfused Langendorff technique, isolated rabbit hearts were arrested for 30 minutes of global normothermic ischemia. Cardioplegia consisted of either Krebs-Henseleit solution alone (control) or with pinacidil (50 micromol/L), adenosine (200 micromol/L to 1 mmol/ L), or pinacidil + adenosine (200 micromol/L). Recovery of developed pressure and coronary flow were recorded.
Postischemic functional recovery for control, pinacidil, adenosine, and adenosine + pinacidil groups was 44.1%+/-3.4%, 59.5%+/-5.2% (p < 0.05 versus control), 37.0%+/-4.5%, and 56.0%+/-2.9%, respectively.
Adenosine, alone or as adjunct to pinacidil cardioplegia, was not an effective cardioplegic agent, despite shorter times to electromechanical arrest than control. The ineffectiveness of adenosine suggests that the cardioprotective properties of potassium-channel openers involve mechanisms other than the avoidance of membrane depolarization.
我们实验室已表明，钾通道开放剂吡那地尔是一种有效的心脏停搏剂。使用钾通道开放剂进行心脏停搏的一个理论益处是，它能使心脏在超极化膜电位下停搏，这是一种代谢需求最小的状态。本研究旨在检验另一种非去极化剂腺苷，并验证其能否提供相当的心脏保护作用或增强钾通道开放剂心脏停搏效果的假设。
采用血液灌注的Langendorff技术，将离体兔心进行30分钟的全心常温缺血停搏。心脏停搏液包括单独的Krebs-Henseleit溶液（对照组）或含吡那地尔（50微摩尔/升）、腺苷（200微摩尔/升至1毫摩尔/升）或吡那地尔+腺苷（200微摩尔/升）的溶液。记录心脏复跳后的收缩压和冠脉流量恢复情况。
对照组、吡那地尔组、腺苷组和腺苷+吡那地尔组缺血后功能恢复率分别为44.1%±3.4%、59.5%±5.2%（与对照组相比，P<0.05）、37.0%±4.5%和56.0%±2.9%。
尽管腺苷导致电机械停搏的时间比对照组短，但单独使用或作为吡那地尔心脏停搏的辅助药物时，腺苷并非有效的心脏停搏剂。腺苷无效表明钾通道开放剂的心脏保护特性涉及避免膜去极化以外的机制。
