Agnes Hajnal, Nagy László, Parratt James R, Papp Julius, Végh Agnes
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P.O. Box 427, H-6701, Hungary.
Cardiovasc Drugs Ther. 2004 Nov;18(6):449-59. doi: 10.1007/s10557-004-6222-2.
The possible involvement of reactive oxygen species (ROS) in the protective effects of ischaemic preconditioning (PC) against arrhythmias was examined in anaesthetised dogs using the ROS scavenger N-2-mercaptopropionylglycine (MPG).
PC was induced in 20 chloralose-urethane anaesthetised dogs by two 5 min occlusions of the left anterior descending (LAD) coronary artery 20 min prior to the prolonged (25 min) ischaemia/reperfusion (I/R) insult. In 10 of these dogs MPG was infused locally into a small side branch of the LAD in a dose of 0.15 mg kg(-1) min(-1), starting 10 min prior to and continuing throughout the entire PC procedure. In another four dogs subjected to preconditioning in the absence and then 2h later in the presence of MPG free radical formation was evaluated by the chemiluminescence method. Eleven dogs, infused with saline and subjected to a 25 min I/R insult, served as controls. A further 9 dogs, which were not preconditioned, were given MPG over a period of 60 min prior to occlusion.
Preconditioning markedly reduced the number of ventricular premature beats (VPBs; 86 +/- 34 v. 377 +/- 78; P < 0.05), the episodes of ventricular tachycardia (VT; 2.0 +/- 0.7 v. 13.6 +/- 4.5; P < 0.05) and the incidences of both VT (60% v. 91%) and ventricular fibrillation (0% v. 82%; P < 0.05) during the prolonged occlusion. Survival (from the combined ischaemia and reperfusion insult) was significantly increased (40% v. 0%; P < 0.05) by PC. MPG did not modify the protective effects of PC, although free radical (mostly superoxide) formation that occurred following PC was abrogated in the presence of MPG. Thus, the number of VPBs (111 +/- 39), VT episodes (1.2 +/- 0.9) and the incidences of VT (20%) and VF (0%) during occlusion were similar to the PC dogs. MPG itself did not significantly modify arrhythmia severity in non-PC dogs.
We conclude that in our canine model of ischaemia/reperfusion the generation of ROS does not play a trigger role in the early PC-induced antiarrhythmic protection.
在麻醉犬中使用活性氧清除剂N - 2 - 巯基丙酰甘氨酸（MPG），研究活性氧（ROS）在缺血预处理（PC）抗心律失常保护作用中的可能参与情况。
对20只氯醛糖 - 乌拉坦麻醉的犬，在延长的（25分钟）缺血/再灌注（I/R）损伤前20分钟，通过两次5分钟阻断左前降支（LAD）冠状动脉诱导PC。在其中10只犬中，从PC程序开始前10分钟起，以0.15毫克/千克（-1）分钟（-1）的剂量将MPG局部注入LAD的一个小侧支，并在整个PC过程中持续注入。在另外4只先进行预处理然后在不存在和2小时后存在MPG的情况下进行预处理的犬中，通过化学发光法评估自由基（主要是超氧阴离子）的形成。11只注入生理盐水并接受25分钟I/R损伤的犬作为对照。另外9只未进行预处理的犬在阻断前60分钟内给予MPG。
预处理显著减少了室性早搏（VPB）的数量（86±34对377±78；P<0.05）、室性心动过速（VT）的发作次数（2.0±0.7对13.6±4.5；P<0.05）以及延长阻断期间VT（60%对91%）和室颤（0%对82%；P<0.05）的发生率。PC显著提高了（联合缺血和再灌注损伤后的）生存率（40%对0%；P<0.05）。MPG并未改变PC的保护作用，尽管在MPG存在的情况下，PC后发生的自由基（主要是超氧阴离子）形成被消除。因此，阻断期间VPB的数量（111±39）、VT发作次数（1.2±0.9）以及VT（20%）和VF（0%）的发生率与PC犬相似。MPG本身在未进行PC的犬中并未显著改变心律失常的严重程度。
我们得出结论，在我们的犬缺血/再灌注模型中，ROS的产生在早期PC诱导的抗心律失常保护中不发挥触发作用。
