Konorev E A, Struck A T, Baker J E, Ramanujam S, Thomas J P, Radi R, Kalyanaraman B
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226.
Free Radic Res Commun. 1993;19(6):397-407. doi: 10.3109/10715769309056529.
The objective of this study was to determine whether inhibition of intracellular catalase would decrease the tolerance of the heart to ischemia-reperfusion and hydrogen peroxide-induced injuries. Isolated bicarbonate buffer-perfused rat hearts were used in the study. Intracellular catalase was inhibited with 3-amino-1,2,4-triazole (ATZ, 1.5 g/kg body weight, two hours prior to heart perfusion). In the ischemia-reperfusion protocol, hearts were arrested with St. Thomas'II cardioplegic solution, made ischemic for 35 min at 37 degrees C, and reperfused with Krebs-Henseleit buffer for 30 min. The extent of ischemic injury was assessed using postischemic contractile recovery and lactate dehydrogenase (LDH) leakage into reperfusate. In the hydrogen peroxide infusion protocol, hearts were perfused with increasing concentrations of hydrogen peroxide (inflow rates 0.05-1.25 mumol/min). Inhibition of catalase activity (30.4 +/- 1.8 mU/mg protein in control vs 2.4 +/- 0.3 mU/mg in ATZ-treated hearts) affected neither pre-ischemic aerobic cardiac function nor post-ischemic functional recovery and LDH release in hearts subjected to 35 min cardioplegic ischemic arrest. Myocardial contents of lipid hydroperoxides were similar in control and ATZ-treated animals after 20 min aerobic perfusion, ischemia, and ischemia-reperfusion. During hydrogen peroxide perfusion, there was an increase in coronary flow rate followed by an elevation in diastolic pressure and inhibition of contractile function in comparison with control hearts. The functional parameters between control and ATZ-treated groups remained unchanged. The concentrations of myocardial lipid hydroperoxides were the same in both groups. We conclude that inhibition of myocardial catalase activity with ATZ does not predispose the rat heart to ischemia-reperfusion and hydrogen peroxide-induced injury.
本研究的目的是确定抑制细胞内过氧化氢酶是否会降低心脏对缺血再灌注及过氧化氢诱导损伤的耐受性。本研究使用了分离的碳酸氢盐缓冲液灌注大鼠心脏。在心脏灌注前两小时，用3-氨基-1,2,4-三唑（ATZ，1.5 g/kg体重）抑制细胞内过氧化氢酶。在缺血再灌注方案中，心脏用圣托马斯II号心脏停搏液停搏，在37℃下缺血35分钟，然后用克雷布斯-亨泽莱特缓冲液再灌注30分钟。使用缺血后收缩恢复和乳酸脱氢酶（LDH）漏入再灌注液来评估缺血损伤的程度。在过氧化氢灌注方案中，心脏用浓度递增的过氧化氢灌注（流入速率0.05 - 1.25 μmol/min）。过氧化氢酶活性的抑制（对照组为30.4±1.8 mU/mg蛋白质，ATZ处理组为2.4±0.3 mU/mg）对经历35分钟心脏停搏缺血的心脏的缺血前有氧心脏功能、缺血后功能恢复及LDH释放均无影响。在20分钟有氧灌注、缺血及缺血再灌注后，对照组和ATZ处理组动物的心肌脂质过氧化物含量相似。在过氧化氢灌注期间，与对照心脏相比，冠状动脉血流速率增加，随后舒张压升高，收缩功能受到抑制。对照组和ATZ处理组之间的功能参数保持不变。两组心肌脂质过氧化物的浓度相同。我们得出结论，用ATZ抑制心肌过氧化氢酶活性不会使大鼠心脏易受缺血再灌注及过氧化氢诱导的损伤。
