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在类似于直接经皮冠状动脉介入治疗(PCI)临床环境的实验模型中,联合应用抗坏血酸和去铁胺静脉治疗以减少心肌再灌注损伤。

Combined intravenous treatment with ascorbic acid and desferrioxamine to reduce myocardial reperfusion injury in an experimental model resembling the clinical setting of primary PCI.

机构信息

Michaelideion Cardiac Center, Ioannina Medical School, Ioannina, Greece.

出版信息

Hellenic J Cardiol. 2012 May-Jun;53(3):195-204.

PMID:22653244
Abstract

INTRODUCTION

During reperfusion of ischemic myocardium, oxygen-derived free radicals are produced and can cause deleterious effects, known as reperfusion injury. We aimed to determine if a combination of the antioxidant ascorbic acid and an iron-chelating agent desferrioxamine, which reduces the production of the hydroxyl radical via ferrum-catalyzed reactions, can exert a protective action against reperfusion injury.

METHODS

Twenty-two young male farm pigs were anesthetized and subjected to 45 mins of ischemia and 3 and a half hours of reperfusion, in the left circumflex coronary artery territory, via the inflation and deflation of an angioplasty balloon. Animals were randomly assigned to receive either an intravenous infusion of 100 mg/ kg ascorbic acid and 60 mg/kg desferrioxamine (treatment group, TG) or an equal amount of normal saline (control group, CG). The I/R ratio, the ratio of the infarcted (necrotic) zone (I) to the myocardial area at risk (R) after 3 and a half hours of reperfusion, was calculated using the tetrazolium staining method. Left ventricular end diastolic pressure (LVEDP), number of episodes of ventricular arrhythmias, TIMI flow in the reperfused vessel, and left ventricular ejection fraction (LVEF) were evaluated within the first hour post reperfusion in order to assess further injury severity.

RESULTS

There was no significant difference in the I/R between the TG (27.9 ± 2.2%) and the CG (32.9 ± 2.4%) (p=0.15). In both groups there was a significant reduction in LVEF (-11.6 ± 2.28% for TG and -12.0 ± 2.27% for CG, p<0.01 for both groups) and a significant increase in LVEDP (+3.2 ± 0.9 mmHg for TG and +4.6 ± 0.9 mmHg for CG, p<0.01 for both groups) compared to the baseline values. No significant difference was noted between groups (p=0.61 for LVEF and p=0.60 for LVEDP values, at one hour post reperfusion). In all other parameters measured, no significant difference was observed between the study groups.

CONCLUSIONS

Intravenous treatment with a combination of the antioxidant ascorbic acid and the iron-chelating agent desferrioxamine does not provide significant protection against myocardial reperfusion injury.

摘要

介绍

在缺血心肌再灌注期间,氧自由基产生,并可能造成有害影响,称为再灌注损伤。我们旨在确定抗氧化剂抗坏血酸和一种铁螯合剂去铁胺的组合是否能发挥保护作用,防止再灌注损伤。抗坏血酸通过铁催化反应减少羟自由基的产生,去铁胺减少铁。

方法

22 只年轻雄性农场猪接受 45 分钟的缺血和 3 个半小时的再灌注,通过球囊充气和放气,在左回旋支冠状动脉区域。动物随机分为静脉输注 100mg/kg 抗坏血酸和 60mg/kg 去铁胺(治疗组,TG)或等量生理盐水(对照组,CG)。用四唑盐染色法计算再灌注 3 个半小时后梗死(坏死)区(I)与危险区(R)的 I/R 比值。在再灌注后 1 小时内评估左心室舒张末期压(LVEDP)、室性心律失常发作次数、再灌注血管的 TIMI 血流和左心室射血分数(LVEF),以进一步评估损伤严重程度。

结果

TG(27.9±2.2%)和 CG(32.9±2.4%)之间的 I/R 无显著差异(p=0.15)。两组 LVEF 均显著降低(TG:-11.6±2.28%,CG:-12.0±2.27%,两组均 p<0.01),LVEDP 显著升高(TG:+3.2±0.9mmHg,CG:+4.6±0.9mmHg,两组均 p<0.01)与基础值相比。再灌注后 1 小时,两组间 LVEF 值(p=0.61)和 LVEDP 值(p=0.60)无显著差异。在所有其他测量参数中,两组间无显著差异。

结论

静脉内用抗氧化剂抗坏血酸和铁螯合剂去铁胺联合治疗并不能提供对心肌再灌注损伤的显著保护。

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