DIRECT EVIDENCE THAT OXYGEN-DERIVED FREE-RADICALS CONTRIBUTE TO POSTISCHEMIC MYOCARDIAL DYSFUNCTION IN THE INTACT DOG
DIRECT EVIDENCE THAT OXYGEN-DERIVED FREE-RADICALS CONTRIBUTE TO POSTISCHEMIC MYOCARDIAL DYSFUNCTION IN THE INTACT DOG
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DOI：
10.1073/pnas.86.12.4695
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发表时间：
1989-06-01
影响因子：
11.1
通讯作者：
MCCAY, PB
中科院分区：
文献类型：
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作者：
BOLLI, R;JEROUDI, MO;MCCAY, PB
用电子顺磁共振(EPR)波谱研究了“顿抑”心肌(有缺血后收缩功能障碍的心肌)产生的自由基是否来源于O2，(Ii)抑制自由基反应改善了功能，以及(Iii)i.v。自旋陷阱是有效的。接受15分钟冠状动脉阻断的开胸犬接受静脉注射。注入自旋陷阱，α-苯基N-叔丁基硝酮(PBN)(50毫克/公斤)。I组(n=6)缺血时冠状静脉血中出现PBN自由基加合物的EPR信号，再灌流后EPR信号明显增强。II组(n=6)，接受PBN和静脉注射。在超氧化物歧化酶(16,000单位/公斤)和过氧化氢酶(12,000单位/公斤)的作用下，心肌在缺血时检测不到PBN加合物的产生(Δ=-100%，P<；0.01vs.I组)，再灌流后显著抑制(Δ=-86%，P<；0.001)。这种影响见于缺血区血流的所有水平，但在低流量范围内相对更大。在III组(n=8)，与对照组(IV组，n=7)相比，相同剂量的SOD和不加PBN的过氧化氢酶显著促进再灌流后3小时的收缩恢复[P<；0.01与对照组(IV，n=7)]。系统血浆超氧化物歧化酶和过氧化氢酶活性平均为127.+-。24和123。+-。再灌流后2min分别为82U/ml。在I组，PBN没有明显的不良反应，实际上改善了缺血后的收缩恢复(与对照组相比，3小时P<；0.05)。这项研究表明：(1)超氧化物歧化酶和过氧化氢酶能有效地阻断体内的自由基反应；(2)“顿抑”心肌产生的自由基来源于氧的单价还原；(3)抑制自由基反应可促进功能恢复。这些结果提供了直接的体内证据，支持了这样的假设，即活性氧代谢产物在短暂缺血后出现的心肌“顿抑”中起着因果作用。
Electron paramagnetic resonance (EPR) spectroscopy was used to investigate whether (i) the free radicals produced in the "stunned" myocardium (myocardium with postischemic contractile dysfunction) are derived from O2, (ii) inhibition of radical reactions improves function, and (iii) i.v. spin traps are effective. Open-chest dogs undergoing a 15-min coronary occlusion received an i.v. infusion of the spin trap, .alpha.-phenyl N-tert-butylnitrone (PBN) (50 mg/kg). In group I (n = 6), EPR signals characteristic of radical adducts of PBN appeared in the coronary venous blood during ischemia and increased dramatically after reperfusion. In group II (n = 6), which received PBN and i.v. superoxide dismutase (SOD; 16,000 units/kg) plus catalase (12,000 units/kg), myocardial production of PBN adducts was undetectable during ischemia (.DELTA. = -100%, P < 0.01 vs. group I) and markedly inhibited after reperfusion (.DELTA. = -86%, P < 0.001). This effect was seen at all levels of ischemic zone flow but was relatively greater in the low-flow range. In group III (n = 8), the same dosages of SOD and catalase without PBN markedly enhanced contractile recovery (measured as systolic wall thickening) after reperfusion [P < 0.01 at 3 hr vs. controls (group IV, n = 7)]. Systemic plasma activity of SOD and catalase averaged 127 .+-. 24 and 123 .+-. 82 units/ml, respectively, 2 min after reperfusion. PBN produced no apparent adverse effects and actually improved postischemic contractile recovery in group I (P < 0.05 at 3 hr vs. controls). This sudy shows that (i) SOD and catalase are highly effective in blocking free radical reactions in vivo, (ii) the radicals generated in the "stunned" myocardium are derived from univalent reduction of O2, and (iii) inhibition of radical reactions improves functional recovery. The results provide direct, in vivo evidence to support the hypothesis that reactive oxygen metabolites play a causal role in the myocardial "stunning" seen after brief ischemia.