Lee C C, Appleyard R F, Byrne J G, Cohn L H
Division of Cardiac Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Cardiovasc Res. 1993 May;27(5):770-3. doi: 10.1093/cvr/27.5.770.
Leukotrienes D4 and E4 are potent coronary vasoconstrictors and myocardial depressants. The aim was to investigate the contribution of myocardial leukotrienes to impairment of coronary flow and recovery of contractile function in rat hearts subjected to 2 h of global ischaemia.
Rat hearts were mounted on a working Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solution at 37 degrees C for 30 min. Hearts were then arrested with either standard potassium crystalloid cardioplegic solution (n = 6), or with cardioplegic solution containing the leukotriene D4, E4 receptor antagonist Ly171883 (n = 6). Arrested hearts were maintained at 15 degrees C for 2 h, then rewarmed to 37 degrees C during 30 min working reperfusion. Coronary effluent was analysed by radioimmunoassay for leukotriene C4, D4, E4, and F4 levels. Immediately prior to cardiac arrest, and again after 30 min reperfusion, coronary flow, and aortic outflow and pressure were measured.
Postischaemic leukotriene levels were increased compared to preischaemic levels in both groups [pooled measurements: 133.3 (SD 136.4) v 20.7(17.8) pg.0.1 ml-1, p < 0.05]. Postischaemic coronary vascular resistance was increased by 80% in controls (p < 0.001) compared to 19% (p = NS) in treated hearts. In addition, functional recovery was significantly greater in treated hearts compared to controls [82(3)% v 53(3)% for coronary flow; 79(3)% v 50(2)% for cardiac output; 82(4)% v 54(3)% for stroke work].
Leukotrienes are endogenously produced by the heart, and this production is significantly increased after global ischaemia and reperfusion. Reversal of significantly increased coronary vascular resistance coupled with improved functional recovery in hearts treated with LY171883 demonstrates an important contribution of endogenously produced leukotrienes to coronary vascular impairment and functional stunning of the globally ischaemic, reperfused heart.
白三烯D4和E4是强效的冠状动脉血管收缩剂和心肌抑制剂。本研究旨在探讨心肌白三烯在大鼠心脏经历2小时全心缺血后对冠状动脉血流受损及收缩功能恢复的影响。
将大鼠心脏置于工作状态的Langendorff装置上，用37℃的含氧Krebs-Henseleit溶液灌注30分钟。然后，心脏分别用标准钾晶体心脏停搏液（n = 6）或含白三烯D4、E4受体拮抗剂Ly171883的心脏停搏液（n = 6）停搏。停搏后的心脏在15℃下保存2小时，然后在30分钟的工作再灌注期间复温至37℃。通过放射免疫分析法分析冠状动脉流出液中白三烯C4、D4、E4和F4的水平。在心脏停搏前及再灌注30分钟后，分别测量冠状动脉血流、主动脉流出量和压力。
两组缺血后白三烯水平均高于缺血前水平[合并测量值：133.3（标准差136.4）对20.7（17.8）pg·0.1 ml-1，p < 0.05]。与治疗组心脏19%（p = 无显著性差异）相比，对照组缺血后冠状动脉血管阻力增加了80%（p < 0.001）。此外，治疗组心脏的功能恢复明显优于对照组[冠状动脉血流：82（3）%对53（3）%；心输出量：79（3）%对50（2）%；每搏功：82（4）%对54（3）%]。
心脏可内源性产生白三烯，在全心缺血及再灌注后其生成显著增加。LY171883治疗的心脏中，显著增加的冠状动脉血管阻力得到逆转，同时功能恢复改善，这表明内源性产生的白三烯对全心缺血再灌注心脏的冠状动脉血管损伤和功能失用有重要影响。
