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全氟溴辛烷乳剂预防性或治疗性应用对大鼠心肌缺血再灌注损伤的影响。

Effects of a prophylactic or therapeutic application of perflubron emulsion on myocardial ischaemia-reperfusion injury in rats.

作者信息

Rempf C, Standl T, Gottschalk A, Freitag M, Ritter A, Lang E, Tuszynski S, Burmeister M A

机构信息

University Hospital, Knappschaftskrankenhaus Bochum Langendreer, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Bochum.

出版信息

Eur J Anaesthesiol. 2008 Oct;25(10):850-9. doi: 10.1017/S0265021508004596. Epub 2008 Jun 9.

Abstract

BACKGROUND AND OBJECTIVE

The efficacy of administering a perfluorochemical-based oxygen therapeutic such as perflubron emulsion (Oxygen) prior to ischaemia is currently unknown, although there is evidence for potential beneficial effects for the perioperative treatment in cardiac risk patients. This experimental study investigated the efficacy of perflubron emulsion in preventing reperfusion injury and myocardial infarction size after coronary ischaemia and reperfusion. The perflubron emulsion was given either in a prophylactic manner, prior to induction of myocardial ischaemia, or as a therapeutic agent given during ischaemia.

METHODS

Thirty-two anaesthetized and mechanically ventilated rats were subjected to 25 min occlusion of the left coronary artery followed by 120 min reperfusion. Animals were randomized to one of four groups:Group 1 was treated with administration of 6 g kg (-1) intravenous perflubron emulsion 25 min before occlusion; Group 2 received the same dose 10 min after occlusion; and Groups 3 and 4 received no perflubron emulsion. Inspired O2 (FiO2) concentration was maintained at 1.0 in Groups 1, 2 and 3 and at 0.35 in Group 4.

RESULTS

Neither prophylactic nor therapeutic perflubron emulsion treatment reduced infarct size measurements by triphenyltetrazolium-chloride staining or severity of cardiac arrhythmias in comparison to the hyperoxic control group. However, prophylactic application of perflubron emulsion reduced areas of impaired perfusion vs. Group 3 assessed by in vivo staining with Thioflavin-S while no significant effect was seen in Groups 2 and 4 vs. 3. Density of DNA single-strand breaks in the ventricle was increased in all groups ventilated with 100% oxygen.

CONCLUSION

Although administration of perflubron emulsion did not reduce infarct size, areas of impaired perfusion were significantly mitigated when perflubron emulsion was administered prior to coronary occlusion. However, a high oxygen concentration may provoke DNA strand breaks during reperfusion after ischaemia. Further studies must clarify whether enhanced oxidative stress outweighs the advantage of improved areas of impaired perfusion following perflubron emulsion.

摘要

背景与目的

尽管有证据表明基于全氟化合物的氧疗剂(如全氟溴辛烷乳剂,即“氧合素”)对心脏风险患者围手术期治疗有潜在益处,但目前尚不清楚在缺血前给予此类药物的疗效。本实验研究调查了全氟溴辛烷乳剂在预防冠状动脉缺血再灌注后再灌注损伤和心肌梗死面积方面的疗效。全氟溴辛烷乳剂以预防性方式在心肌缺血诱导前给予,或作为治疗剂在缺血期间给予。

方法

32只麻醉并机械通气的大鼠接受左冠状动脉25分钟阻断,随后再灌注120分钟。动物被随机分为四组之一:第1组在阻断前25分钟静脉注射6 g/kg全氟溴辛烷乳剂;第2组在阻断后10分钟接受相同剂量;第3组和第4组未接受全氟溴辛烷乳剂。第1、2和3组的吸入氧(FiO2)浓度维持在1.0,第4组维持在0.35。

结果

与高氧对照组相比,预防性或治疗性全氟溴辛烷乳剂治疗均未通过氯化三苯基四氮唑染色减少梗死面积测量值或降低心律失常的严重程度。然而,与第3组相比,预防性应用全氟溴辛烷乳剂通过硫黄素-S体内染色评估减少了灌注受损区域,而第2组和第4组与第3组相比未见显著效果。所有用100%氧气通气的组心室中DNA单链断裂密度均增加。

结论

尽管给予全氟溴辛烷乳剂并未减少梗死面积,但在冠状动脉阻断前给予全氟溴辛烷乳剂时,灌注受损区域显著减轻。然而,高氧浓度可能在缺血后再灌注期间引发DNA链断裂。进一步研究必须阐明增强的氧化应激是否超过全氟溴辛烷乳剂后灌注受损区域改善的优势。

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