人类心脏再灌注期间的氧化应激：氧自由基的潜在来源。

Oxidative stress during reperfusion of human hearts: potential sources of oxygen free radicals.

作者信息

Curello S, Ceconi C, de Giuli F, Panzali A F, Milanesi B, Calarco M, Pardini A, Marzollo P, Alfieri O, Messineo F

机构信息

Università degli Studi di Brescia, Italy.

出版信息

Cardiovasc Res. 1995 Jan;29(1):118-25.

PMID:7895229

Abstract

OBJECTIVE

The aim was to examine the role of neutrophil activation in the genesis of oxidative stress during the early phases of reperfusion after ischaemia in patients subjected to aortocoronary bypass grafting.

METHODS

Ten selected patients were studied. All had normal ejection fraction and normal left ventricular end diastolic pressures before operation. Each patient required at least three grafts, so that the duration of aortic crossclamping exceeded 30 min, the minimum ischaemic period required to detect oxidative stress upon reperfusion. Oxidative stress was assessed by measuring the formation and release of oxidised glutathione (GSSG) in the coronary sinus 1 min before and 3 min after the start of the cardiopulmonary bypass, and then 1, 5, 10, and 20 min after removal of the aortic clamp, and again 5 and 10 min after the end of the cardiopulmonary bypass. The arterial-coronary sinus difference for neutrophils, elastase-alpha 1 protease complex (elastase), and creatine phosphokinase was also monitored at the same intervals.

RESULTS

Before clamping GSSG was undetectable in arterial and coronary sinus blood. There was no significant arterial-coronary sinus difference for neutrophils or elastase [53(SEM 66) cell.ml-1 and 1.10(2.49) micrograms.litre-1, respectively[. Five minutes after re-establishment of coronary blood flow, there was both a release of GSSG into the coronary sinus [arterial-coronary sinus difference: 11(2.6) nmol.dl-1] and an accumulation of neutrophils in the heart [arterial-coronary sinus difference: 262(33), P < 0.01 cell.ml-1], whereas no elastase release from the heart was measured [arterial-coronary sinus difference 7.6(4.46) microgram.litre-1, NS]. The arterial levels of elastase increased progressively during the operation from 48(5) microgram.litre-1 (preclamping) to 405(62) microgram.litre-1, P < 0.01 (end of the cardiopulmonary bypass).

CONCLUSIONS

These data indicate that, in man, neutrophils do accumulate in the myocardium during early reperfusion. However, they are not activated when oxidative stress occurs. It is unlikely that the neutrophil localisation in the heart has pathological significance in the production of oxygen free radicals during early reperfusion. Free radical accumulation in the coronary vessels may contribute to disorders of coronary flow associated with reperfusion.

摘要

目的

本研究旨在探讨在接受主动脉冠状动脉搭桥术的患者缺血后再灌注早期，中性粒细胞激活在氧化应激发生过程中所起的作用。

方法

选取10例患者进行研究。所有患者术前射血分数和左心室舒张末期压力均正常。每位患者至少需要三根移植血管，因此主动脉阻断时间超过30分钟，这是检测再灌注时氧化应激所需的最短缺血时间。通过测量体外循环开始前1分钟和开始后3分钟，以及松开主动脉夹后1、5、10和20分钟，再灌注结束后5和10分钟时冠状窦中氧化型谷胱甘肽（GSSG）的生成和释放情况来评估氧化应激。同时在相同时间间隔监测中性粒细胞、弹性蛋白酶-α1蛋白酶复合物（弹性蛋白酶）和肌酸磷酸激酶的动静脉冠状窦差值。

结果

阻断前，动脉血和冠状窦血中均未检测到GSSG。中性粒细胞或弹性蛋白酶的动静脉冠状窦差值无显著差异[分别为53（标准误66）个细胞·ml⁻¹和1.10（2.49）μg·L⁻¹]。恢复冠状动脉血流5分钟后，GSSG释放到冠状窦中[动静脉冠状窦差值：11（2.6）nmol·dl⁻¹]，同时心脏中中性粒细胞积聚[动静脉冠状窦差值：262（33），P<0.01个细胞·ml⁻¹]，而未检测到心脏有弹性蛋白酶释放[动静脉冠状窦差值7.6（4.46）μg·L⁻¹，无显著性差异]。手术过程中动脉血弹性蛋白酶水平从48（5）μg·L⁻¹（阻断前）逐渐升高至405（62）μg·L⁻¹，P<0.01（体外循环结束时）。