缺血预处理对鼠后肢缺血再灌注下脊髓腰骶膨大运动神经元的保护作用

[目的]对大鼠一侧后肢的缺血再灌注损伤行不同条件缺血预处理,观察脊髓腰骶膨大处运动神经元超微结构的变化,探讨其保护作用.[方法]通过血管夹暂时阻断大鼠左侧髂总、髂内和髂外动脉,建立大鼠后肢缺血模型.以缺血6h再灌注2h和12 h分为A、B两组,预处理方式为缺血10 min血液复流10 min,按无预处理、预处理1次、无时间间隔预处理2、3次,分成A0、A1、A2、A3;B0、B1、B2、B3组.取材腰骶膨大处脊髓灰质前角,光镜及透射电镜下观察不同条件预处理对缺血再灌注损伤中脊髓前角超微结构变化.[结果]组织形态观察结果显示A0组缺血再灌注损伤后神经元细胞减少,核溶解消失,损伤明显,预处理后神经元细胞增多,可见部分细胞核存在;B0组缺血再灌注损伤后神经元细胞大部分坏死溶解,预处理后坏死溶解现象减轻.超微结构观察显示A0和B0组脊髓前角神经兀细胞不同程度核周器扩张损伤,出现内质网扩张、大量线粒体空泡以及核膜溶解消失.预处理后损伤程度有所减轻,叠加预处理后损伤进一步减轻.[结论]缺血预处理能减轻大鼠肢体缺血再灌注下脊髓腰骶膨大运动神经元的损伤,对脊髓具有保护作用.反复3次预处理产生的保护作用优于2次预处理及1次预处理.     

甲基强的松龙与钙蛋白酶抑制剂对大鼠缺血再灌注损伤脊髓保护作用比较

[目的]观察脊髓缺血再灌注损伤后应用甲基强的松龙和钙蛋白酶抑制剂E-64-D,脊髓组织钙蛋白酶表达和活性的变化及对动物后肢功能的影响.[方法]纯种雄性成年SD大鼠,夹闭右肾动脉分支下腹主动脉30 min,造成动物脊髓缺血再灌注损伤(B组),再灌注后静脉应用钙蛋白酶特异性抑制剂E-64-D(C组)或甲基强的松龙(D组),观察3、24、72 h和7 d后脊髓损伤节段的钙蛋白酶的表达,及钙蛋白酶特异性底物68-KD NFP的降解和动物后肢功能情况.[结果]脊髓再灌注损伤后3 h,开始出现的钙蛋白酶阳性细胞,于再灌注后72 h最明显.68-KD NFP的降解产物也在再灌注损伤后3 h出现,并在72 h后达到高峰.应用E-64-D和甲基强的松龙后,钙蛋白酶的表达和68-KD NFP的降解得到抑制,而且E-64-D的抑制作用明显强于甲基强的松龙,结果具有显著性差异(P＜0.01).[结论]脊髓缺血再灌注损伤后两种治疗方法均可不同程度地保护脊髓组织和动物后肢的运动功能.     

丹酚酸B联合高氧液对兔肢体再灌注损伤保护作用

[目的]探讨高氧液和丹酚酸B对兔肢体再灌注损伤的保护作用.[方法]选用健康新西兰家兔24只,随机分为4组,在缺血前从耳缘静脉推注等虽的生理盐水(A组)、高氧液(B组)、丹酚酸B(C组)或高氧液加丹酚酸B(D组),夹阻股动静脉,建立肢体缺血再灌注损伤模型,在缺血前和再灌注4 h抽血检测丙二醛(MDA)和超氧化物岐化酶(SOD),取腓肠肌作病理检测.[结果]再灌注损伤后血清丙二醛浓度较前明显升高,丹酚酸B组、高氧液组以及丹酚酸B联合高氧液组的MDA升高均受到抑制(P<0.01),以丹酚酸B联合高氧液组最为明显;血清超氧化物岐化酶活性较前明显降低,丹酚酸B组、高氧液组以及丹酚酸B联合高氧液组的SOD降低均受到抑制(P<0.01),以丹酚酸B联合高氧液组最为显著.骨骼肌HE染色见丹酚酸B联合高氧液组骨骼肌损伤程度最轻.[结论]丹酚酸B联合高氧液和对兔肢体缺血再灌注损伤具有一定的保护作用,且两者有协同作用.     

缺血后处理和预处理对大鼠骨骼肌缺血-再灌注损伤的作用

目的 探讨缺血后处理( IPost)和缺血预处理(IPC)对大鼠骨骼肌缺血再灌注(IR)损伤的影响.方法 将40只大鼠随机分成缺血再灌注组(A组)、缺血后处理组(B组)、缺血预处理组(C组)、缺血预处理加缺血后处理组(D组)以及对照组(E组),采用切断患肢全部皮肤、肌肉和神经,保留患肢股动、静脉的动物模型,通过夹闭和开放股动、静脉造成骨骼肌缺血再灌注损伤,通过测定骨骼肌缺血4h、再灌注1h后血清丙二醛(MDA)和骨骼肌髓过氧化物酶(MPO),以及再灌注6h后骨骼肌的坏死程度来观察缺血后处理.缺血预处理及缺血预处理加缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响.结果 B组、C组和D组再灌注1 h MDA和MPO水平以及再灌注6h骨骼肌坏死程度均低于A组(P＜ 0.05),但是高于E组(P＜0.05);B组和D组再灌注1 h MDA和MPO水平以及再灌注6h骨骼肌坏死程度基本相同(P＞0.05);B组和D组再灌注1 h MDA和MPO水平低于C组(P＜0.05),但再灌注6h骨骼肌坏死程度基本相同(P＞0.05).结论 应用缺血后处理和缺血预处理对大鼠骨骼肌缺血再灌注损伤有一定的保护效果,联合应用缺血后处理和缺血预处理,对骨骼肌缺血再灌注损伤的保护作用并没有明显增强.     

姜黄素对骨骼肌缺血再灌注损伤的保护作用及其机制研究

目的:观察姜黄素对肢体骨骼肌缺血再灌注损伤中血浆肌酸磷酸激酶(CPK)、乳酸脱氢酶(LDH)、丙二醛(MDA)含量及骨骼肌99m锝亚甲基二磷酸钠(99mTcMDP)吸收量的影响,探讨姜黄素对肢体骨骼肌缺血再灌注损伤的保护作用及其机制。方法:制作大鼠后肢缺血再灌注损伤模型,30只大鼠随机分为假手术组、对照组、干预组。分别于再灌注1 h后测定血浆CPK、LDH、MDA含量和腓肠肌99mTcMDP吸收量变化,透射电镜观察腓肠肌超微结构变化。结果:缺血再灌注对照组和姜黄素干预组与假手术组相比,血浆CPK(7296.18±1086.53,5168.49±975.39,3014.26±963.78)、LDH(1203.66±282.53,726.56±203.65,463.85±75.32)、MDA(10.36±2.65,6.78±2.12,3.54±1.89)含量明显增高(P<0.01),99mTcMDP吸收量(16.69±3.14,11.45±2.35,9.12±1.96)明显升高(P<0.01);腓肠肌超微结构损伤明显加重;姜黄素组血浆和骨骼肌的各项指标与缺血再灌注对照组相比显著降低(P<0.01),腓肠肌超微结构损伤明显减轻。结论:姜黄素能有效降低血浆CPK、LDH、MDA含量,减少骨骼肌99mTcMDP吸收量,减轻缺血再灌注骨骼肌坏死程度和坏死范围,改善骨骼肌再灌注损伤的超微结构,说明姜黄素对骨骼肌缺血再灌注损伤具有明显的保护作用。     

三种灌注液对断指再植组织再灌注损伤保护作用的研究

目的 研究三种不同灌注液对断肢再植后缺血再灌注损伤的保护作用。方法 建立大鼠后肢的断肢再植模型，应用3种不同灌注液（A组肝素钠组，B组肝素钠＋利多卡因组，C组肝素钠＋地塞米松组）对离断肢体进行灌注，然后进行再植。分别于缺血前、缺血6h、通血60min取材，测定断肢皮肤中丙二醛（MDA）、透射电镜观察缺血6h后再通血60min血管内膜的改变。结果 3组再植肢体成活率相当，B组灌注前后MDA差值明显低于A组，差异有统计学意义。B组、C组血管内膜改变较A组轻微。结论 断肢再植前应用含利多卡因、地塞米松灌注液对离断指进行灌注，可以减轻再植肢体的缺血再灌注损伤，且对血管内膜有保护作用。     

缺血预处理对兔骨骼肌再灌注损伤延迟保护作用的实验研究

目的探讨缺血预处理对兔骨骼肌再灌注损伤是否存在早期、延迟保护作用及保护程度。方法选择30只新西兰大白兔随机等分为对照组、早期保护组(EP)和延迟保护组(DP)。对照组直接用气囊止血带阻断兔后肢血流4h,造成骨骼肌缺血再灌注损伤模型。EP和DP组先进行缺血预处理,分别在预处理后立即和24h后用气囊止血带阻断兔后肢血流4h造成缺血再灌注模型。测定再灌注期血清中肌酸磷酸激酶(CPK)、天门冬酰胺氨基转移酶(AST)和超氧化物歧化酶(SOD)含量,光、电镜下观察骨骼肌结构变化。结果再灌注后1、2、4、8h,EP与DP组血清中CPK和AST的含量均明显低于对照组(P<0.01);SOD含量明显高于对照组(P<0.01),而EP与DP组之间差异无显著性意义(P>0.05)。骨骼肌线粒体空泡变性和肌原纤维溶解均延迟出现,其病变程度明显轻于对照组。结论缺血预处理不仅存在早期、延迟保护作用,且均能提高骨骼肌对长时间缺血的耐受能力,减轻骨骼肌缺血再灌注损伤程度,这两种保护作用的程度无明显差异。     

硫酸镁对兔脊髓缺血再灌注损伤保护作用的研究

目的:探讨硫酸镁对兔脊髓缺血再灌注损伤的保护效果。方法:27只新西兰大白兔,随机分为A组(硫酸镁处理组)、B组(生理盐水)和C组(假手术对照组)。A、B两组参照Tetik方法建立兔脊髓腰骶段缺血模型,比较三组动物不同时间点的体感诱发电位(SEP)、后肢运动功能评分及缺血再灌注后48h的病理学改变。结果:C组SEP没有明显变化,动物均完全康复。缺血30min时B组波形消失,A组波幅降为基线的(29.3±1.9)%。再灌注60min后A组、B组SEP波幅分别渐升致基线的(74.5±2.3)%和(49.2±2.1)%。A组N1、P1波峰潜伏期在缺血30min及再灌注60min时均明显优于B组(P<0.05);再灌注24h和48h后,A组的后肢运动功能评分均显著高于B组(P<0.05);再灌注48h后A组的脊髓前角神经细胞计数显著高于B组(P<0.01)。结论:硫酸镁具有减轻兔脊髓缺血再灌注损伤及保护神经功能的作用。     

兔脊髓分级缺血-再灌注损伤对体感诱发电位的影响

目的 了解不同程度脊髓缺血-再灌注损伤与体感诱发电位（SEP）、神经功能评分及脊髓病理改变的关系。方法 将40只新西兰大耳白兔随机均分为4组，假手术组、缺血30min组、缺血45min组和缺血60min组。采用腹主动脉阻断法建立兔脊髓缺血-再灌注损伤模型，分别于缺血前、缺血5、10min、再灌注15、30min、1、2、24和48h监测SEP。于再灌注6、12、24和48h进行神经功能评分，再灌注48h进行脊髓病理学观察。结果 阻断腹主动脉血流30、45和60min后开放分别表现为轻、中、重度缺血-再灌注损伤脊髓的病理学改变特点。脊髓轻度缺血-再灌注损伤中SEP波幅和潜伏期分别于再灌注15和30min时恢复至缺血前水平（P〉0．05）；脊髓中度缺血-再灌注损伤中SEP波幅和潜伏期分别于再灌注30min和再灌注1h恢复至缺血前水平（P〉0．05）；脊髓重度缺血-再灌注损伤中SEP波幅和潜伏期分别明显下降和延长，与其他各组组间比较差异有统计学意义（P〈0.01）。各组神经功能评分组间比较差异均有统计学意义（P〈0. 01）。结论 脊髓缺血-再灌注损伤中SEP波幅较潜伏期恢复迅速。术中SEP监测能够敏感而准确地反映缺血-再灌注损伤中脊髓功能的变化，可为临床应用提供实验依据。     

缺血后处理对骨骼肌缺血再灌注损伤的保护作用

任何组织的缺血,只要达到一定时间和程度,必然会引起组织细胞的损伤.1985年McCord经过研究发现,长时间的组织器官缺血后的再灌注是一把"双刃剑",首先是再灌注挽救了缺血的组织器官,以防止进一步的缺血损伤,然而不可控的再灌注也引起了组织器官的再灌注损伤,故此提出了缺血一再灌注损伤这一概念.骨骼肌是组成肢体的重要组织之一,同时它对缺血十分敏感,人类骨骼肌在室温下完全缺血2.25 h就会出现不可逆的功能损害.在骨科的临床工作中,动脉断裂栓塞、断肢再植、应用止血带时间过长,都有可能造成严重的骨骼肌缺血,随后发生缺血再灌注损伤,从而影响患者肢体的存活,甚至造成截肢的后果.     

大蒜素对兔急性下肢缺血再灌注损伤后组织中IL-1,IL-6,IL-8含量的影响

目的 观察大蒜素注射液对兔急性下肢缺血再灌注损伤后组织中白介素-1、白介素-6、白介素-8含量的影响及意义.方法 30只家兔随机分为5组：空白组、缺血再灌注2h组、缺血再灌注5h组、缺血再灌注2h大蒜素治疗组、缺血再灌注5h大蒜素治疗组.复制缺血再灌注模型.空白组,切开下肢,点滴生理盐水,取腓肠肌.其余四组于缺血2h或5h结束前10min,分别于耳缘静脉点滴大蒜素或生理盐水,再灌注1h后取腓肠肌.分别作免疫指标测定和形态学观察,进行对比分析.结果 缺血再灌注2h组、5h组组织中IL-1,IL-6,IL-8含量与空白组比较有明显增高（P〈0.05）,而缺血再灌注2h大蒜素治疗组、缺血再灌注5h大蒜素治疗组分别与缺血再灌注2h组、缺血再灌注5h组比较IL-1、IL-6、IL-8含量明显下降（P〈0.05）.光镜观察,再灌注组组织结构改变明显,而治疗组改变较轻.结论 大蒜素在兔急性下肢缺血再灌注损伤中能抑制IL-1,IL-6,IL-8的表达,有效减少中性粒细胞的黏附、浸润,减轻炎性渗出,押制微循环通透性的增加,减轻下肢肌肉的损伤.     

Polyadenosine diphosphate-ribose polymerase inhibition modulates skeletal muscle injury following ischemia reperfusion

HYPOTHESIS: Polyadenosine diphosphate-ribose polymerase (PARP) has been implicated as a mediator of inflammation and tissue necrosis in murine models of human stroke and myocardial infarction. This study was designed to determine whether PARP modulates skeletal muscle injury and cytokine-growth factor levels during ischemia-reperfusion. DESIGN: Prospective controlled animal study. SETTING: Medical school-affiliated university hospital. INTERVENTIONS: Mice were divided into 2 groups-treated (PJ) and untreated; all mice were subjected to unilateral hind limb tourniquet ischemia followed by 4 or 48 hours of reperfusion. In treated mice, PJ34, an ultrapotent-specific PARP inhibitor was given immediately before ischemia and prior to reperfusion. A group of PARP-1 knockout mice (PARP-/-) were also subjected to hind limb ischemia followed by 48 hours of reperfusion. MAIN OUTCOME MEASURES: After ischemia-reperfusion, muscle was harvested for measurement of edema, viability, cytokine, and vascular endothelial growth factor content. RESULTS: The PJ34-treated mice had increased skeletal muscle viability when compared with the untreated mice after 4 and 48 hours of reperfusion (P<.01). Viability between PARP-/- and PJ34-treated mice were similar at 48 hours of reperfusion (P>.05), and it exceeded that of untreated mice (P<.01). Tissue edema was unaltered by PARP inhibition. Tissue levels of cytokine were only different (P<.05) in PJ34-treated vs untreated mice at 48 hours of reperfusion. Vascular endothelial growth factor levels in PJ34-treated mice were markedly reduced when compared with untreated mice only after 4 hours of reperfusion (P<.01), and in PARP-/- mice (P<.01) at 48 hours of reperfusion. CONCLUSIONS: Polyadenosine diphosphate-ribose polymerase modulates skeletal muscle viability, cytokine and vascular endothelial growth factor synthesis during reperfusion. Polyadenosine diphosphate-ribose polymerase inhibition may represent a novel method to modulate skeletal muscle ischemia-reperfusion injury.     

Permeability changes following ischemia-reperfusion injury in the rabbit hindlimb.

Changes in permeability following ischemia-reperfusion injury were assessed in the intact rabbit hindlimb by measuring the transvascular clearance of 125I-labeled rabbit serum albumin. Ischemia was induced for periods of 1 or 2 hours by use of a pneumatic tourniquet inflated to 300 mmHg. Following ischemia, the limb was reperfused for 1, 2, or 3 hours. The albumin clearance in the gastrocnemius muscle of control rabbits was 5.1 +/- 0.7 (mean +/- SEM) microliters/hr/g dry weight. Following 1 hour of ischemia and reperfusion, muscle albumin clearance rose to 71.4 +/- 26 microliters/hr/g dry weight which was not significantly different from those animals that underwent 2 hours of ischemia. Muscle albumin clearance continued to be elevated following 2 hours of reperfusion; however, it returned toward control levels after 3 hours of reperfusion. These data suggest there is a transient increase in albumin permeability following ischemia-reperfusion injury in skeletal muscle.     

Early systemic effects of hind limb ischemia-reperfusion on hemodynamics and acid-base balance in the rat

We investigated the systemic hemodynamic effects and the early arteriovenous acid-base changes after 2-h tourniquet ischemia on left hind limb in rats during the first hour of reperfusion. The right femoral artery and vein were prepared and catheterized for direct blood pressure monitoring and blood sampling. In ischemia-reperfusion group, 5 min before releasing the tourniquet and during the first hour of the reperfusion (5', 10', 15', 30', 45', and 60'), arterial and venous blood samples were taken in parallel with a sham operated control group. In the ischemia-reperfusion group venous pH continuously decreased during reperfusion and was significantly lower compared to control and base in the 60th min, while arterial pH remained almost unchanged. PCO2 and pO2 showed moderate signs of a parallel respiratory compensation. Mean arterial pressure decreased almost by 20%, heart rate slightly increased during reperfusion. Our data indicates that besides the general effects anesthesia, limb ischemia-reperfusion results in hemodynamic and acid-base changes during the first hour of reperfusion.     

Reduced ischemia-reperfusion injury in muscle Experiments in rats with EPC-K1, a new radical scavenger

L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1 -benzopyran-6-yl hydrogen phosphate] potassium salt (EPC-K1), a phosphate diester of alpha-tocopherol and ascorbic acid, is a potent antioxidant. We examined the effects of EPC-K1 on ischemia-reperfusion injury in the skeletal muscle of rats, using an ischemic revas-cularized hind limb model. Warm ischemia (25 C), produced by vascular pedicle clamping, was sustained for 4 hours. After 24 hours of reperfusion, skeletal muscle injury was evaluated in 2 groups: one group treated by intravenous injection of EPC-K1 (10 mg/kg) prior to ischemia, and a group of controls. The EPC-K1 -treated group showed a statistically significant amelioration in the reduction of the isometric muscle contraction, inhibition of the elevation of the muscle wet- to dry-weight ratio, limitation of the muscle level of thiobarbituric acid reactive substances and the serum levels of creatine phos-phokinase, lactate dehydrogenase and mitochondrial glutamic oxaloacetic transaminase, and reduction of the extent of muscle injury according to the histological findings. These observations indicate that EPC-K1 acted effectively on ischemia-reperfusion injury in the rat skeletal muscle and thereby improved muscle function.     

Serial morphological changes in primate skeletal myofibres after 3 hours of ischaemia and 24 hours of reperfusion.

The sequential morphological changes occurring in skeletal myofibres after 3 hours' ischaemia and from 3 hours to 24 hours of reperfusion in vervet monkeys are described. Eight vervet monkeys were studied under general anaesthesia. A hind limb was exsanguinated and a tourniquet applied for 3 hours. Open muscle biopsy specimens were obtained from the tibialis anterior muscle before tourniquet application, just before tourniquet release and 3, 6, 12, 18 and 24 hours after tourniquet deflation. All specimens were prepared for transmission electron microscopy. After 3 hours of ischaemia and increasing periods of reperfusion, a small number of fibres showed progressive pathomorphological changes that eventually resulted in myofibre death. After initial glycogen loss and later intermyofibrillar oedema, the majority of myofibres returned to normal, while a group of fibres remained oedematous. The progressive morphological characteristics of reversibly injured myofibres undergoing repair and irreversible injured cells undergoing necrosis are described.     

Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion in rabbit hind limbs

Background Glycyrrhizin, an agent that can bind to selectins and inhibit their ability to bind neutrophils, was found to be effective in preventing tissue edema caused by ischemia-reperfusion in a rabbit model. Methods Complete ischemia was produced by applying a tight Esmarch tourniquet to the hind limbs of 24 Japanese white rabbits. Immediately before and 1 h after release of the tourniquet, 12 animals were given glycyrrhizin intravenously; 12 controls received saline. Results The mean relative increase in the circumference of the shins before and after ischemia-reperfusion with or without glycyrrhizin treatment was 4.6% ± 2.4% and 9.6% ± 4.2%, respectively, indicating that tissue edema caused by the ischemia-reperfusion was significantly attenuated by glycyrrhizin. Histological studies of cross sections of the anterior tibial muscle 24 h after reperfusion showed a significant reduction in the incidence of necrotic muscle fibers in the glycyrrhizin-treated animals compared with the controls that did not receive glycyrrhizin. The mRNA levels of P- and E-selectin 24 h after reperfusion were significantly higher in the ischemic anterior tibial muscle than in the nonischemic normal muscle. After 24 h of reperfusion, the mean activity of myeloperoxidase, a neutrophil-specific enzyme, in the anterior tibial muscles of the group given glycyrrhizin (0.0022 ± 0.0013 absorbance units) was lower than that of the untreated group (0.027 ± 0.026 absorbance units). Conclusions These data suggest that glycyrrhizin treatment is effective in suppressing the acute inflammatory reaction or edema following ischemia-reperfusion and might be potentially useful in clinical practice for preventing ischemia-reperfusion injuries to the extremities.     

Lower Limb Ischemia-Reperfusion Injury Triggers a Systemic Inflammatory Response and Multiple Organ Dysfunction

Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.     

Cuff Width Increases the Serum Biochemical Markers of Tourniquet-induced Skeletal Muscle Ischemia in Rabbits

Tourniquet application is a widely accepted adjuvant technique in extremity surgery. The purpose of this prospective, randomized trial was to evaluate the effect of cuff width on skeletal muscle ischemia-reperfusion injury. A 2- or 4-cm wide curved tourniquet cuff was applied around the midthigh of 36 New Zealand White rabbits and inflated to a pressure of 200 or 400 mm Hg for 2 hours: group A=2 cm to 200 mm Hg; group B=2 cm to 400 mm Hg; group C=4 cm to 200 mm Hg; group D=4 cm to 400 mm Hg. Blood levels of potassium, lactic acid, urea, lactic dehydrogenase, and creatinine phosphokinase MM isoenzyme (CPK-MM) were measured as basic indicators for limb ischemia before tourniquet inflation and 1, 5, and 30 minutes after cuff release.Potassium values did not differ among the 4 groups. Lactic acid and urea concentrations were always higher in the 400 mm Hg groups (B and D) (P<.001). However, cuff width did not affect their levels (P>.16). Lactic dehydrogenase and CPK-MM values were also greater in the 400 mm Hg groups at all times (P<.001). Further subgroup analysis of 200 mm Hg pressure groups showed higher lactic dehydrogenase (P<.02) but not CPK-MM (P>.9) concentrations in group C than in group A during the 30-minute period. At 400 mm Hg, lactic dehydrogenase and CPK-MM values were higher in group D compared with group B only 30 minutes after cuff deflation (P<.001).Broad tourniquets are associated with significantly greater and prolonged elevation of serum biochemical markers of inducible skeletal muscle ischemia-reperfusion injury compared with narrow ones. This difference is more prominent when a wide cuff is inflated to a high pressure.