THE EFFECT OF SUPEROXIDE-DISMUTASE IN THE MYOCARDIUM DURING REPERFUSION IN THE DOG
THE EFFECT OF SUPEROXIDE-DISMUTASE IN THE MYOCARDIUM DURING REPERFUSION IN THE DOG
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DOI：
10.1016/0891-5849(92)90147-9
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发表时间：
1992-11-01
影响因子：
7.4
通讯作者：
FEHER, J
中科院分区：
文献类型：
--
作者：
KONYA, L;KEKESI, V;FEHER, J
为探讨自由基在心肌再灌注损伤中的病理作用，在犬冠状动脉左前降支（LAD）结扎后29 min和再灌注前1 min，分别向左心房内注入低剂量（0.5mg/kg体重）和高剂量（5 mg/kg体重）超氧化物歧化酶（SOD）4 min。在结扎（30 min）和再灌注（20 min）期间监测动脉血压、心率、心电图和左心室局部收缩力。分别于结扎前（0 min）、结扎过程中（15 min和25 min）及再灌注过程中（2 min、7 min和20 min）测定冠状窦血中肌酸激酶（CK）和丙二醛（MDA）的浓度。在其他组的狗，两种剂量的SOD对心外膜血流的影响进行了研究，在结扎和再灌注期间，通过测量心外膜温度，使用热心描记器。实验对象为杂种狗，雌雄不限（n = 25），体重10-35 kg。与对照组相比（平均值+/- SEM，43.1 +/-1.2; n = 7），再灌注前5分钟的室性期外收缩次数显著增加，（p < .001）在高剂量给药犬中降低（15.01 +/- 2.14; n = 5），但在接受低剂量药物的患者中没有（34.6 +/- 5.66; n = 5）。CK浓度逐渐升高，至再灌注结束，各组间无差异。对照组再灌注后7 min血浆MDA含量最高。局部收缩力，这是大大减少，在结扎过程中，在所有组，表现出缓慢的改善，在再灌注期间，并达到79.5%的结扎前水平，在低剂量的SOD组，74.7%，和96.3%的高剂量。在对照犬（-0.03 ℃; n = 2）和接受低剂量药物的犬（-0.05 ℃; n = 2）中，LAD结扎导致心外膜温度突然下降，随后缓慢下降，直至结扎结束。相比之下，接受高剂量SOD的犬在结扎期结束时表现出心外膜温度轻微升高（0.06 ℃; n = 2）。与对照组（0.58 ℃; 8 min，10 s）和低SOD组（0.59 ℃; 8 min，7 s）相比，高剂量SOD（0.77 ℃; 7 min，37 s）治疗组动物的充血反应更明显，发作更早。高剂量的SOD减少室性期前收缩的数量，改善心肌收缩，并增加心外膜血流量在LAD再灌注期间的观察表明，短暂心肌缺血后自由基的病理作用。
The aim of the study was to investigate the pathological role of free radicals during myocardial reperfusion, Low(0.5 mg/kg body weight) and high doses (5 mg/kg) of superoxide dismutase (SOD) were infused into the left atrium of mongrel dogs for 4 min starting 29 min after ligation and 1 min before reperfusion of the left anterior descending coronary artery (LAD). Arterial blood pressure, heart rate, electrocardiogram, and the regional contractile force of the left ventricle were monitored throughout the ligation (30 min) and reperfusion periods (20 min). Concentrations of creatine kinase (CK) and malondialdehyde (MDA) in the coronary sinus blood were determined before (0 min) and during ligation (15 and 25 min) and during reperfusion of the LAD (2, 7, and 20 min). In other groups of dogs, the effect of the two doses of SOD on epicardial blood flow was investigated during ligation and reperfusion by the measurement of epicardial temperature using a thermocardiograph. Experimental subjects were mongrel dogs of either sex (n = 25), weight 10-35 kg. Compared to controls (mean +/- SEM, 43.1 +/-1.2; n = 7), the number of ventricular extrasystoles during the first 5 min of reperfusion was significantly (p < .001) decreased in dogs treated with the high dose (15.01 +/- 2.14; n = 5), but not in those receiving the low dose of the drug (34.6 +/- 5.66; n = 5). The concentrations of CK increased gradually until the end of reperfusion without differences among the different groups. Plasma MDA was the highest in control dogs 7 min after reperfusion. Regional contractile force, which was substantially reduced in all groups during ligation, showed a slow improvement during reperfusion and reached 79.5% of the preligation level in controls, 74.7% in the low dose, and 96.3% in the high dose of SOD groups. Ligation of the LAD produced a sudden drop of epicardial temperature followed by a slow decrease until the end of ligation in control dogs (-0.03-degrees-C; n = 2) and those receiving the low dose of the drug (-0.05-degrees-C; n = 2). In contrast, dogs receiving the high dose of SOD exhibited a slight increase of epicardial temperature at the end of the ligation period (0.06-degrees-C; n = 2). The hyperemic response was more pronounced with an earlier onset in the animals treated with the high dose of SOD (0.77-degrees-C; 7 min, 37 s) compared to those found in controls (0.58-degrees-C; 8 min, 10 s) and in the low SOD group (0.59-degrees-C; 8 min, 7 s). The observations that a high dose of SOD decreased the number of ventricular extrasystoles, improved myocardial contraction, and increased epicardial blood flow during reperfusion of the LAD suggest a pathological role for free radicals after transient myocardial ischemia.