巯基化合物对缺血再灌流所致大鼠离体心脏功能低下的保护作用

比较观察了半胱氨酸(Cys),N-乙酰半胱氨酸(NAC)及胱胺(CSSC)对Langendorff灌流大鼠心脏缺血再灌所致心功能低下的保护作用。心脏平衡后开始给药(3.6μmol/min)直至实验结束。Cys和NAC可使心脏缺血再灌后的LVP、±dP/dt和RPP迅速恢复至结扎前的水平,并显著高于生理盐水对照组,CSSC则未见有这些保护作用。三药均可使结扎期的冠脉流量明显高于对照。所试药物对Fenton反应生成的OH均有不同程度的清除,Cys的效果最强。

Protective effects of sulfhydryl-compounds on ischemia-reperfusion induced myocardial dysfunction in isolated rat hearts

The protective effects of cysteine the left anterior descending coronary artery (LAD) for (Cys), N-acetylcysteine (NAC) and cystamine (CSSC) 20 minntes and followed by 30 min reperfusion were on myocardial dysfunction induced by the ligation of studied in the isolated Langendorff perfused rat hearts.The hearts were perfused with Cys, NAC and CSSC at the rate of 3.6 μmol/min, n = 7-8. Perfusion of nor mal saline (NS) and sham ligation operation served as control. In NS control at 20 min after ligation the LVP, +dP/dt, -dP/dt and rate pressure product (RPP) were depressed to 45, 41, 33 and 31% of their preischemic functions, respectively. The recovery of these functions at 30 min reperfusion was 87, 82, 71 and 74%, respectively. The recovery of the LVP, -dP/dt, +dP/dt and RPP during the entire reperfusion period was 89-112% of their preischemic functions in the Cys and NAC treated groups, which were significantly (p< 0.05-0.001) higher than those in the NS group. The LVP, ±dP / dt and RPP in CSSC were substantially lower than those in the NS. Coronary flow (CF) in Cys, NAC and CSSC were significantly higher than those in the NS. the scavenging effects of these drugs on O(-·2) and OH radicals were studied in irradiation of the riboflavin and Fenton's reaction systems with spin trapping ofDMPO and ESR technology in vitro. The second peak's heights of ESR spectra of DMPO adducts generated from the Fenton's system of the Cys, NAC, and CSSC treated groups were 2181 ?437, 4161±1723 and 4014±1827, respectively, which were lower than those in the NS control (7674±2638). The results suggested that Cys as well as NAC exerted remarkable protective effects on ischemia-reperfusion induced myocardial dysfunction. The mechanism of the drug action might be related to the scavenging effect on OH radicals, the improvement of the CF of ischemic myocardium and the protective effects of free SH group on bioactive proteins.