心脏停搏液中的钾通道开放剂可能恢复冠状动脉内皮功能。
Potassium-channel opener in cardioplegia may restore coronary endothelial function.
作者信息
He G W
机构信息
Department of Surgery, University of Hong Kong, Grantham Hospital, Aberdeen.
出版信息
Ann Thorac Surg. 1998 Oct;66(4):1318-22. doi: 10.1016/s0003-4975(98)00794-2.
BACKGROUND
Depolarizing (hyperkalemic) solutions impair the coronary endothelial function through an endothelium-derived hyperpolarizing factor mechanism. I examined the hypothesis that potassium-channel openers may restore the impaired endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation when added to hyperkalemic cardioplegia.
METHODS
The porcine coronary arteries were exposed to hyperkalemia (potassium, 20 or 50 mmol/L) or hyperkalemia plus the potassium-channel opener aprikalim at 0.1 mmol/L for 1 hour. Endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of 30 nmol/L U46619 precontraction) was induced by calcium ionophore A23187 and bradykinin in the presence of indomethacin (7 micromol/L) and Nomega-nitro-L-arginine (300 micromol/L).
RESULTS
The endothelium-derived hyperpolarizing factor-mediated relaxation was significantly impaired by exposure to hyperkalemia (20 mmol/L: 24.9%+/-14.1% versus 88.0%+/-3.3% in control, p = 0.002 for A23187; 50 mmol/L: 40.5%+/-12.3% versus 76.5%+/-3.8%, p = 0.003 for bradykinin). This reduced relaxation was significantly recovered by addition of aprikalim into the hyperkalemic (20 mmol/L) solution in A23187 experiments (81.2%+/-4.8%, p = 0.002) but only slightly recovered when added into the higher concentration of potassium (50 mmol/L) in bradykinin experiments (56.1%+/-4.7%, p = 0.2).
CONCLUSIONS
Potassium-channel openers may preserve endothelium-derived hyperpolarizing factor-mediated coronary relaxation when added to traditional hyperkalemic cardioplegia. This effect is significant when the potassium concentration is 20 mmol/L but partially lost when it reaches 50 mmol/L. This study may provide new insights into cardioprotection during open heart operations.
背景
去极化（高钾血症）溶液通过内皮衍生的超极化因子机制损害冠状动脉内皮功能。我检验了这样一个假设，即钾通道开放剂添加至高钾血症心脏停搏液中时，可能恢复受损的内皮衍生的超极化因子介导的冠状动脉血管舒张功能。
方法
将猪冠状动脉暴露于高钾血症（钾浓度为20或50 mmol/L）或高钾血症加0.1 mmol/L钾通道开放剂阿普卡林中1小时。在存在吲哚美辛（7 μmol/L）和Nω-硝基-L-精氨酸（300 μmol/L）的情况下，由钙离子载体A23187和缓激肽诱导内皮衍生的超极化因子介导的舒张（30 nmol/L U46619预收缩的百分比）。
结果
暴露于高钾血症会显著损害内皮衍生的超极化因子介导的舒张功能（20 mmol/L：24.9%±14.1%，而对照组中A23187介导的为88.0%±3.3%，p = 0.002；50 mmol/L：40.5%±12.3%，而缓激肽介导的对照组为76.5%±3.8%，p = 0.003）。在A23187实验中，将阿普卡林添加至高钾血症（20 mmol/L）溶液中可显著恢复这种降低的舒张功能（81.2%±4.8%，p = 0.002），但在缓激肽实验中添加至较高浓度钾（50 mmol/L）溶液中时仅略有恢复（56.1%±4.7%，p = 0.2）。
结论
钾通道开放剂添加至传统高钾血症心脏停搏液中时，可能保留内皮衍生的超极化因子介导的冠状动脉舒张功能。当钾浓度为20 mmol/L时，这种作用显著，但当达到50 mmol/L时部分丧失。本研究可能为心脏直视手术期间的心脏保护提供新的见解。
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