猪冠状动脉内皮细胞舒张过程中高钾溶液的抑制作用(英文)

Protective effects of high potassium solution in the relaxation process of endothelium in porcine coronary arteries

背景:目前高钾心脏停搏液已在心脏手术中广泛应用。但有关高钾溶液对冠状动脉内皮细胞舒张血管功能影响的研究尚少。 目的:探讨高钾溶液对猪冠状动脉内皮细胞功能的影响及其机制。 设计:随机对照的实验研究。 地点、材料和干预:2000-06/09从北京大红门肉联厂共取17只刚宰杀的生猪猪心(雌雄不限)。均置入4℃的KH中,30min内送回北京阜外医院体外循环研究室,10min内选其心外膜下冠状动脉前降支中下三分之一,切成3段3mm的血管环。按单纯随机抽样法将49条猪冠状动脉血管环分为7组,每组7条;分别为对照组、20mmol/L高钾组、50mmol/L高钾组、四乙胺组、格列苯脲(商品名:优降糖)组、50mmol/L高钾+四乙胺组、50mmol/L高钾+格列苯脲组。采用器官槽法,分别用Krebs-Henseleit重碳酸盐缓冲液(Krebs solution, KH)、20,50mmol/L的高钾溶液浸泡血管环1h。 主要观察指标:7μmol/L环加氧酶阻断剂吲哚美辛(商品名:消炎痛)和300μmol/L一氧化氮合成酶阻断剂N-硝基-L-精氨酸、1mmol/L钙激动性钾通道阻断剂四乙胺或3μmol/L ATP敏感性钾通道阻断剂优降糖的作用下,30nmol/L前列腺素F_(2α)。引发的预收缩强度和非受体介导钙离子载体(1×10^(-10)～1×10^(-6)mol/L)引发的内皮源性舒张反应。 结果:格列苯脲组。

BACKGROUND:Now high potassium solutions have widely been used for myocardial protection in cardiac surgery and for preservation of various organs for transplantation,but the reports about effects of high potassium solution on endothelium in coronary arteries were less. OBJECTIVE:To investigate that effects of high potassium solution on endothelium function in porcine coronary arteries and the possible mechanism.DESIGN:The way of simple random sampling conducted between June 2000 and September 2000. SETTING,PARTICIPANTS and INTERVENTION:Coronary arteries were obtained from seventeen porcine hearts that were harvested in a local Dahongmeng abattoir.Immediately after the hog(either sex) was killed,the heart was rapidly removed,placed in a container filled with Krebs solution at 4℃,and transferred to the laboratory in 30 min.The one third lower site of anterior descending epicardial coronary artery in one porcine heart was taken and cut into three parts about 3 mm long in 10 min.Fourty-nine coronary rings were randomly divided into 7 groups,seven pieces in each:control group,20 K+ group,50 K+ group,tetraethylammonium group,glibenclamide group,50 K+ and tetraethylammonium group,50 K+ and glibenclamide group.Porcine coronary artery rings were studied in the organ chambers and incubated,with Krebs-Henseleit (KH),20 or 50 mol/L K+ for 1 h.MAIN OUTCOME MEASURES:Relaxation in response to the EDHF stimuli A23187 in 1146619-induced precontraction in the presence of 7μmol/L indomethacin(a cyclooxygenase inhibitor) and 300μmol/L L-NNA (a nitric oxide biosyhnthesis inhibitor),1 mmol/L tetraethylammonium (a Ca2+ activated K+ channelblocker),or 3μmol/Lglibenclamide(an ATP-sensitive K+ channel blocker),were compared. RESULTS:The precontraction forces in the glibenclamide group,50 K+ and tetraethylammonium group,50 K+ and glibenclamide group were( 1.0±0.3),(1.2±0.5) and(1.9±0.8) g,respectively,significantly different from that in the control group[ (2.4±0.5) g,F = 11.425,P <0.05].The relaxation could be further inhibited by tetraethylammonium,and 20 or 50 mol/L K+ (0.007,0.008,0.006),but not glibenclamide(0.351).CONCLUSION:Endothelium-derived hyperpolarizing factors(EDHF)-mediated relaxation in coronary arteries are reduced by exposure to hyper-kalemia;Ca2+ activated K+ channels are likely to be involved in ED-HF-mediated relaxation in coronary arteries.