Skjelbakken T, Valen G, Vaage J
Division of Thoracic and Cardiovascular Surgery, University of Tromsø, Norway.
Scand J Clin Lab Invest. 1996 Aug;56(5):431-9. doi: 10.3109/00365519609088798.
A model of cardiac dysfunction induced by reactive oxygen species (ROS) was established by adding hydrogen peroxide (H2O2) to the perfusate of isolated, Langendorff-perfused rat hearts, and the mechanism of functional injury was investigated. The following groups were included: 1 (n = 7), control perfusion; 2 (n = 11), perfusion with H2O2 (180 mumol 1(-1) for 10 min followed by recovery for 50 min; 3 (n = 4), control perfusion with N-acetylcysteine (NAC, 100 mumol 1(-1); 4 (n = 7), perfusion with H2O2 and NAC; 5 (n = 4), control perfusion with thiourea (15 mmol 1(-1), 6 (n = 7), H2O2 and thiourea together; 7 (n = 4), control perfusion with catalase (150 U ml-1); 8 (n = 7), catalase and H2O2, 9 (n = 4), control perfusion with deferoxamine (5 mmol 1(-1); and 10 (n = 7), deferoxamine and H2O2. coronary flow (CF), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and heart rate (HR) were measured. All values are mean +/- SEM. When given alone, catalase, thiourea, NAC and deferoxamine did not influence left ventricular pressures, but NAC, catalase and thiourea increased CF. H2O2 increased CF (maximum 146 +/- 6% of baseline value after 5 min, p < 0.001 compared to group 1), decreased LVDP (minimum 14 +/- 5% of baseline value after 10 min, p < 0.0004), and increased LVEDP (from 0 mmHg to a maximum of 54 +/- 7 mmHg after 5 min recovery, p < 0.0003). All these changes gradually reversed during recovery. Catalase and thiourea both inhibited the H2O2-induced effects, but catalase inhibition was more complete. Neither NAC nor deferoxamine had any effect on H2O2-induced cardiac dysfunction. In conclusion, H2O2 perfusion is a convenient and reversible model of ROS-induced functional injury to isolated rat hearts. H2O2, rather than the hydroxyl radical, seems to be the main injurious ROS in this model.
通过向离体的、经Langendorff灌注的大鼠心脏灌注液中添加过氧化氢（H2O2）建立活性氧（ROS）诱导的心脏功能障碍模型，并研究功能损伤的机制。实验分组如下：1组（n = 7），对照灌注；2组（n = 11），用H2O2灌注（180 μmol·L-1，持续10分钟，随后恢复50分钟）；3组（n = 4），用N-乙酰半胱氨酸（NAC，100 μmol·L-1）进行对照灌注；4组（n = 7），用H2O2和NAC灌注；5组（n = 4），用硫脲（15 mmol·L-1）进行对照灌注；6组（n = 7），H2O2和硫脲共同灌注；7组（n = 4），用过氧化氢酶（150 U·ml-1）进行对照灌注；8组（n = 7），过氧化氢酶和H2O2共同灌注；9组（n = 4），用去铁胺（5 mmol·L-1）进行对照灌注；10组（n = 7），去铁胺和H2O2共同灌注。测量冠状动脉血流量（CF）、左心室舒张末压（LVDP）、左心室舒张末压（LVEDP）和心率（HR）。所有数值均为平均值±标准误。单独给予时，过氧化氢酶、硫脲、NAC和去铁胺对左心室压力无影响，但NAC、过氧化氢酶和硫脲可增加CF。H2O2可增加CF（5分钟后最高达到基线值的146±6%，与1组相比，p < 0.001），降低LVDP（10分钟后最低降至基线值的14±5%，p < 0.0004），并增加LVEDP（恢复5分钟后从0 mmHg最高升至54±7 mmHg，p < 0.0003）。所有这些变化在恢复过程中逐渐逆转。过氧化氢酶和硫脲均抑制H2O2诱导的效应，但过氧化氢酶的抑制作用更完全。NAC和去铁胺对H2O2诱导的心脏功能障碍均无影响。总之，H2O2灌注是一种简便且可逆的ROS诱导的离体大鼠心脏功能损伤模型。在该模型中，似乎是H2O2而非羟基自由基是主要的致伤性ROS。
