REVERSAL OF THE POSTISCHEMIC CHANGES IN SKELETAL-MUSCLE BLOOD-FLOW AND VIABILITY BY A NOVEL INHIBITOR OF LIPID-PEROXIDATION

被引：12

作者：

HOMERVANNIASINKAM, S ^{[1
]}

HARDY, SC ^{[1
]}

GOUGH, MJ ^{[1
]}

机构：

[1] GEN INFIRM,GREAT GEORGE ST,LEEDS LS1 3EX,W YORKSHIRE,ENGLAND

来源：

EUROPEAN JOURNAL OF VASCULAR SURGERY | 1993年 / 7卷 / 01期

关键词：

VASCULAR SURGERY; REPERFUSION INJURY; 21-AMINOSTEROIDS; U74500A;

D O I：

10.1016/S0950-821X(05)80542-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The role of a novel inhibitor of lipid peroxidation (U74500A) in modifying post-ischaemic changes in skeletal muscle blood flow, viability and oedema has been investigated in a rat model of 6 h unilateral hindlimb ischaemia followed by 4 h reperfusion. During reperfusion, gastrocnemius muscle blood flow (GMBF) was measured (radiolabelled microspheres) at 10, 120 and 240 min and a perfusion index (PI) calculated between the reperfused and contralateral normal limb. Muscle viability (GMV-nitroblue tetrazolium) and oedema (wet:dry weight ratio, reperfused: contralateral limb) were assessed after 4 h reperfusion. GMBF in untreated controls, compared to normal animals, demonstrated a triphasic pattern of low reflow at 10 min [PI 0.08 (0.01-0.13) vs. 1.05 (0.68-1.18), p <0.01], relative reperfusion at 120min [PI 0.29 (0.09-0.59) vs. 0.97 (0.79-1.13), p < 0.05] and reperfusion injury at 240 min [PI 0.05 (0.01-0.14) vs. 1.01 (0.73-1.16), p < 0.01] with a median GMV at 240 min of 52.9% (33.3-61.4), p < 0.01 vs. normals and 6h ischaemia alone (GMV 100% in all limbs) and an oedema index of 1.23 (1.09-1.37 p < 0.01 vs. normal. In contrast, rats receiving U74500A (2 mg/kg i.v. infusion commencing 30 min prior to revascularisation) exhibited enhanced GMBF throughout reperfusion [PI 10 min : 3.26 (2.56-3.63); 120 min : 2.03 (1.73-2.25); 240 min: 2.13 (1.75-2.44), p < 0.01 vs. controls and normals] with complete muscle salvage [GMV 100% in all reperfused muscles, p < 0.01 vs. controls, not significant (Ns) vs. normals and 6 h ischaemia]. Reperfusion oedema still occurred however [oedema index 1.33 (1.00-1.37), p < 0.05 vs. normals and 6h ischaemia, ns vs. controls]. These results demonstrate a central role for lipid peroxidation in the pathogenesis of skeletal muscle reperfusion injury and suggest that adjuvant therapy with lipid peroxidation inhibitors may improve limb salvage rates following surgery for acute lower limb ischaemia. © 1993 Grune & Stratton Ltd.

引用

页码：41 / 45

页数：5

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