Free radical injury in skeletal muscle ischemia and reperfusion.

This study was made in a canine isolated gracilis muscle model to measure directly the free radicals, to predict the severity of ischemia and reperfusion injury of the skeletal muscle by measuring its surface pH (mspH), and to determine the effect of Coenzyme Q10 (CoQ10) in reducing the extent of muscle injury. Animals were divided into three groups: group A (control, n = 10), group B (untreated, n = 10), and group C (CoQ10 treated, n = 10). In both groups B and C, 5 hr ischemia followed by 40 min of reperfusion was made. Free radicals were measured directly by electron spin resonance spectrometer (ESR) and mspH was measured using a pH microprobe. Serum creatine phosphokinase (CPK) was estimated before ischemia, 5 and 30 min after reperfusion. The extent of muscle injury was evaluated morphologically by Evan's blue dye exclusion test. ESR intensity in group B was 0.55 +/- 0.19 and decreased to 0.30 +/- 0.04 in group C (P less than 0.01). Rate of recovery of mspH was higher in group C (7.16 +/- 0.06) compared to group B (6.88 +/- 0.11, P less than 0.01) and CPK in group C was less (847 +/- 381 IU/liter) than in group B (1356 +/- 519 IU/liter, P less than 0.05) after 30 min of reperfusion. In group C the morphological muscle injury was less (37.8 +/- 5%) compared to group B (56.7 +/- 3.6%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemia/reperfusion injury in skeletal muscle

Ischemia reperfusion injury to skeletal muscle may be explained by a cascade of cellular and systemic events initiated by an ischemic period followed by reperfusion. During the period of ischemia there is a gradual reduction of intracellular energy stores. Adenosine triphosphate is gradually depleted despite the buffering effect of creatine phosphate which is present in large stores in muscles. As well, glycogen stores are depleted with resultant production of small amounts of energy and large accumulations of lactate. Upon reperfusion there is a reactive hyperemia, resulting in an overall increase in muscle blood flow, despite the fact that areas may continue to be underperfused. Results of this blood flow are mixed with the beneficial effects of removing metabolic by-products and supplying exogenous substrates and oxygen. However, this blood flow also causes harmful effects by washing out necessary precursors for adenine nucleotide resynthesis. Production of oxygen free radicals occurs with resultant membrane lipid peroxidation, and calcium influx occurs upon reoxygenation with resultant disruption of oxidative rephosphorylation in the mitochondria. The sequestration of white blood cells in the muscle due to up regulation of both neutrophil receptors and endothelial leukocyte adhesion molecules results in a prolongation of the reperfusion injury. This subsequently results in damage to remote organs, including lung, heart, and kidneys. The future for therapeutic interventions aimed at reducing this injury lie mostly in the ability to modulate the reperfusion effect.     

The influence of arachidonic acid metabolites on leukocyte activation and skeletal muscle injury after ischemia and reperfusion.

Derivatives of arachidonic acid have been found to play a role in the reperfusion injury of various tissues. These compounds have a broad spectrum of activity, including modulation of white blood cell response to injured tissue. This study was designed to determine the effect of thromboxane and lipoxygenase derivatives on the local and systemic response to ischemia and reperfusion of skeletal muscle. Fifteen dogs were separated into three groups and subjected to gracilis muscle ischemia followed by 2 hours of reperfusion. One group served as controls, one group was treated with OKY-046 (a thromboxane synthetase inhibitor), and one group was treated with diethylcarbamazine (a lipoxygenase inhibitor). White blood cell activation as measured by superoxide anion production, and eicosanoid levels were measured both in the gracilis venous effluent and central venous circulation. These results were compared to infarct size in the gracilis muscle. OKY-046 significantly reduced thromboxane production in both the central venous (102 +/- 30 to 31 +/- 9 pg/ml, p less than 0.05) and gracilis samples (107 +/- 22 to 25 +/- 6 pg/ml, p less than 0.005). This was accompanied by a reduced white cell activation in the central venous blood (15 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.05), but did not affect infarct size or white cell activation in the gracilis. Conversely, diethylcarbamazine significantly reduced both white cell activation (16 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.005) and infarct size in the gracilis muscles (61.6% +/- 4.5% to 28.5% +/- 8.6%, p less than 0.01), as well as reduced systemic white blood cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury

BACKGROUND: Glycine (GLY) is a neutral amino acid that has been shown to be cytoprotective in the kidneys of dogs and rabbits undergoing ischemia-reperfusion injury. To investigate whether GLY exhibits a protective effect on skeletal muscle subjected to ischemia and reperfusion injury, we used a well-described gracilis muscle model in canines. METHODS: Twelve adult mongrel dogs were subjected to 6 hours of ischemia in 1 randomly selected side. The dogs were randomized into 2 groups: group 1 (6 animals) underwent 15 minutes of perfusion with 2.2% GLY, and group 2 (6 animals) underwent 15 minutes of perfusion with normal saline solution (NS) only. Both groups had normothermic reperfusion for 1 hour along with the corresponding perfusate. Muscle biopsy specimens were taken, frozen in liquid nitrogen, and stored at -70 degrees C. Muscle injury was evaluated at 48 hours by measuring weight gain (edema), maximal contractile force, and percent of muscle necrosis. Adenosine triphosphate (ATP) and phosphocreatine (Pcr) (an energy store for ATP synthesis) levels were determined by using high performance liquid chromatography. RESULTS: In group 1, the average weight gain was 57% +/- 11.27% while in group 2 it was 100% +/- 12.48%. Maximal muscle contractile force was 712.5 +/- 68 g for group 1 and 511 +/- 27.91 g for group 2. The amount of muscle necrosis was 30 +/- 3.7% in group 1, as opposed to 63 +/- 10% in group 2. The ATP content was 0.07 +/- 0.03 nmol/mg wet tissue weight (post-ischemia with NS) and 0.21 +/- 0.08 nmol/mg wet tissue weight (post-ischemia with GLY). Pcr content was 0.19 +/- 0.04 mmol/mg wet tissue weight (post-ischemia with NS) and 0.27 +/- 0.04 micromol/mg wet tissue (post-ischemia and infused with GLY) (P <.05). CONCLUSIONS: These data show that GLY preserves muscle function, decreases edema and the amount of muscle necrosis and preserves energy stores in this canine model. Because GLY can be safely given systemically in human beings in higher concentrations than that given in our model, as it is given in parenteral nutrition, its mechanism of action should be further investigated for its potential use in the clinical setting of ischemia and reperfusion injury.     

Inosine attenuates tourniquet-induced skeletal muscle reperfusion injury

BACKGROUND: Adenosine attenuates skeletal muscle reperfusion injury, but its short half-life in vivo limits potential therapeutic benefits. The aim of this study was to ascertain whether inosine, a stable adenosine metabolite, modulates skeletal muscle reperfusion injury. MATERIALS AND METHODS: C57BL/6 mice were randomized (8-10 per group) to six groups: time controls; inosine (100 mg/kg) before anesthesia; 2 h of bilateral tourniquet hindlimb ischemia; I/R (2 h of bilateral tourniquet hindlimb ischemia, 3 h of reperfusion); inosine (100 mg/kg) before I/R; drug vehicle before I/R. Serum tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 were measured before ischemia and at the end of reperfusion. Tissue edema was determined by wet/dry weight ratios. Tissue leucosequestration was assessed by the myeloperoxidase (MPO) content. RESULTS: At the end of reperfusion, inosine pretreatment resulted in lower MPO levels in muscle (P = 0.02) and lung (P = 0.0002) than saline pretreatment. Similarly, muscle (P = 0.04) and lung (P = 0.02) wet/dry ratios were significantly reduced with inosine but not with saline pretreatment. At the end of reperfusion, serum proinflammatory cytokine levels (TNF-alpha and MIP-2) were significantly reduced (P < 0.05) compared to preischemia levels following inosine pretreatment but not saline pretreatment. Ischemia alone did not alter any of the parameters assessed. CONCLUSIONS: These findings demonstrate that pretreatment with inosine attenuates the local and systemic proinflammatory responses associated with skeletal muscle reperfusion injury.     

Therapeutic interventions against reperfusion injury in skeletal muscle

Ischemia/reperfusion (I/R) injury in the skeletal muscle is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive and transplantation surgeries. Although skeletal muscle has a higher tolerance to ischemia than other organs, prolonged ischemia can still result in significant complications, including muscle necrosis and apoptosis. One of the major goals in the treatment of ischemia is early restoration of blood flow (reperfusion) to the area at risk. However, reperfusion has led to a new pathophysiologic condition called "reperfusion injury," a phenomenon which actually provokes a distinct degree of tissue injury. The purpose of this review is to examine the current state of understanding of I/R injury as well as to highlight recent developments on I/R interventions including our own experience in this particular field. We expect, as our acquired experience and the increased knowledge of underlying mechanisms of I/R injury, more effective interventions aimed to reduce I/R injury will be developed to interfere with or modulate this particular pathophysiologic processes.     

S-nitroso-n-acetylcysteine protects skeletal muscle against reperfusion injury

The effects of a nitric oxide (NO) donor on microcirculation and contractile function of reperfused skeletal muscle were studied. Rat cremaster muscles underwent 5 hours of ischemia and 90 minutes of reperfusion and were divided into two groups systemically infused with S-nitroso-N-acetylcysteine (SNAC, 100 nmol/ min) and phosphate-buffered saline (PBS), respectively. The results showed that the vessels in the SNAC group had more rapid and complete recovery than that in controls. A significant difference was found from 10 to 40 minutes and at 90 minutes in 10–20-μm arterioles, from 10 to 90 minutes in 20–40-μm arterioles, and at 10 and 90 minutes in 40–70-μm arteries. When compared to controls, SNAC-treated muscles showed larger fluorescein filling areas at 15, 30, 60, and 90 minutes and greater isometric tetanic contractile forces in response to stimulation frequencies of 40, 70, 100, and 120 Hz. The data indicate that supplementation of exogenous NO could effectively improve microcirculation and contractile function of skeletal muscle during early reperfusion. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:299–305, 1998     

Rate of reperfusion blood flow modulates reperfusion injury in skeletal muscle

The mechanisms of ischemia-reperfusion (I-R) injury in skeletal muscle remain controversial. We investigated the effect of the rate of reperfusion blood flow on I-R injury in an isolated in vivo canine gracilis muscle model in six anesthetized dogs. In all animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. During reperfusion, one gracilis artery was partially occluded to limit the rate of reperfusion blood flow to its preischemic rate (limited reperfusion, LR), while the contralateral artery was allowed to perfuse freely at a normal rate (normal reperfusion, NR). Muscle injury was quantified by histochemical staining (triphenyltetrazolium chloride, TTC) with computerized planimetry of the infarct size, and by spectrophotometric determination of technetium-99m pyrophosphate uptake. Endothelial permeability was quantified by measurement of gracilis muscle weight gain and 125I-albumin radioactivity after intravenous injection. Results are presented as the means +/- SEM, and differences are considered to be statistically significant if P less than 0.05 by Student's t test for paired data. LR resulted in significantly less blood flow (9.7 +/- 1.7 cc/min/100 g) when compared to NR (55.7 +/- 11.6 cc/min/100 g). I-R injury was significantly reduced by LR as evidenced by a decrease in TTC infarct size from 41 +/- 7% to 11 +/- 5%, and a decrease in technetium-99m pyrophosphate uptake from 512 +/- 20 to 163 +/- 44 X 10(3) counts/min/g. LR also significantly decreased the postreperfusion edema formation as evidenced by a reduction in the muscle weight gain from 27 +/- 6 to 9 +/- 1 g, and a reduction in the 125I-albumin radioactivity from 45 +/- 14 to 32 +/- 8 counts/min/g. These data suggest that the hyperemic rate of reperfusion blood flow is a significant factor in the pathophysiology of postreperfusion edema and that clinical control of reperfusion injury in skeletal muscle may be achieved by limiting the rate of reperfusion blood flow.     

Activated protein C attenuates skeletal muscle ischaemia reperfusion injury.

Aims: Pharmacological modulation of skeletal muscle reperfusion injury after an ischaemic insult may improve limb salvage rates and prevent the associated systemic sequelae. Activated Protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties that has been extensively studied in the setting of sepsis. The purpose of our study was to evaluate the effects of APC on skeletal muscle ischaemia reperfusion injury. Methods: Adult male Sprague Dawley rats (n = 24) were randomised into three groups: control group, I/R group treated with normal saline and I/R group treated with APC. Bilateral hind-limb ischaemia was induced by rubber band application proximal to the level of the greater trochanters for two hours. Treatment groups received either normal saline or APC prior to tourniquet release. Following twelve hours reperfusion, the tibialis anterior was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Skeletal muscle injury was assessed based on myeloperoxidase content as a measure of neutrophil infiltration and wet to dry ratio as a measure of oedema formation. Histological analysis was also performed on the muscle. Results: APC significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle (Table). These findings were supported by our histological findings. Statistical significance was determined using variance analysis. Conclusion: Activated Protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury.     

Statins inhibit neutrophil infiltration in skeletal muscle reperfusion injury

BACKGROUND: Neutrophil infiltration is a major determinant of ischemia-reperfusion injury (IRI). Statins improve endothelial function by elevating nitric oxide synthase activity and inhibiting adhesion molecule expression and may, therefore, inhibit IRI-induced neutrophil extravasation. Although statins are protective against myocardial IRI and stroke, a role for statins in ameliorating skeletal muscle IRI has not yet been confirmed. This study, therefore, addressed the hypothesis that simvastatin would attenuate the severity of tissue damage during skeletal muscle IRI. METHODS: Rats were administered simvastatin for 6 d before 4 h hind limb ischemia and 24 h reperfusion. Neutrophil infiltration was assessed using myeloperoxidase (MPO) assays and tissue damage by quantitative immunohistochemical analysis of collagen IV. The effect of reducing nitric oxide levels on the severity of IRI was assessed by administering the NOS inhibitor, N-Imino-L-ornithine (L-NIO), before ischemia. RESULTS: Simvastatin significantly inhibited IRI-induced MPO activity but not collagen degradation in postischemic skeletal muscle. Inhibition of nitric oxide synthase by L-NIO markedly inhibited neutrophil infiltration and protected against IRI-induced collagen degradation. When both simvastatin and L-NIO were administered before IRI, the IRI-induced elevation in MPO activity was completely inhibited. However, paradoxically, simvastatin counteracted the protective effect of L-NIO against IRI-induced collagen IV degradation. CONCLUSIONS: The inhibition by simvastatin of IRI-induced neutrophil infiltration in skeletal muscle suggests that statins may be a useful therapy to attenuate the severity of IRI but their precise mechanisms of action remains to be determined. Nitric oxide also plays a cytotoxic, rather than protective, role in mediating IRI in this model.     

Allopurinol--a free radical scavenger--reduces reperfusion injury in skeletal muscle

Reperfusion of ischaemic skeletal muscle may lead to increased vascular permeability, oedema and ultimately muscle necrosis. Oxygen-derived free radicals have been suggested as aetiological factors in reperfusion injury. Amputated rabbit hindlimbs were subjected to 4 h of ischaemia followed by 2 h or reperfusion with Krebs' buffer. One limb from each animal was reperfused with oxygen-saturated buffer (reoxygenated limb) while the other limb was reperfused with nitrogen-saturated buffer (non-reoxygenated limb). Six animals received allopurinol orally 2 days prior to the experiment and ten animals received no treatment. The energy charge dropped from 0.90 to 0.54 during ischaemia and increased to 0.82 after reperfusion with oxygenated perfusate. Oedema was determined by limb weight and water content in muscle biopsies and muscle injury was assessed by uptake of [Tc99]methylenediphosphonate ([Tc99]MDP). The results were expressed in ratios, between the reoxygenated and nonreoxygenated limb. Without allopurinol treatment, the increase in water content and limb weight in reoxygenated limbs exceeded (p less than 0.05) non-reoxygenated limbs (ratios = 1.73 and 1.89, respectively). Allopurinol treatment significantly reduced (p less than 0.05 and p less than 0.02, respectively) the increase in water content and limb weight (ratios = 0.54 and 1.01, respectively). Without treatment, [Tc99]MDP-uptake was greater (p less than 0.05) in reoxygenated limbs than in non-reoxygenated limbs (ratio = 1.60). Allopurinol treatment significantly reduced (p less than 0.002) [Tc99]MDP-uptake in reoxygenated limbs (ratio = 0.80). These results demonstrate that additional injury to ischaemic skeletal muscle occurs during reperfusion with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pravastatin attenuates tourniquet-induced skeletal muscle ischemia reperfusion injury

Background Revascularization of a limb following prolonged ischemia results in substantial skeletal muscle injury. Statins play a well-understood role in the treatment of hypercholesterolemia but are also known to have anti-inflammatory properties. The purpose of this study was to examine the effects of pravastatin pre-treatment in the setting of skeletal muscle ischemia reperfusion injury (IRI).

Methods Adult male Sprague Dawley rats (n = 27) were randomized into 3 groups: control group, I/R group, IR group pre-treated with pravastatin. Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 h. Treatment groups received normal saline in equal volumes prior to tourniquet release. Following 12 h reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then killed and skeletal muscle harvested for evaluation.

Results We found that pre-treatment with pravastatin reduces the tissue oxidative damage and edema associated with skeletal muscle reperfusion injury. Skeletal muscle injury, measured by edema, leucose-questration and electrical properties were significantly lower with pravastatin pre-treatment compared to the non-treated group.

Interpretation We feel that pravastatin pre-treatment may be a potential therapeutic intervention for skeletal muscle ischemia reperfusion injury in the clinical setting. ▪     

Pravastatin attenuates tourniquet-induced skeletal muscle ischemia reperfusion injury

Background?Revascularization of a limb following prolonged ischemia results in substantial skeletal muscle injury. Statins play a well-understood role in the treatment of hypercholesterolemia but are also known to have anti-inflammatory properties. The purpose of this study was to examine the effects of pravastatin pre-treatment in the setting of skeletal muscle ischemia reperfusion injury (IRI).

Methods?Adult male Sprague Dawley rats (n = 27) were randomized into 3 groups: control group, I/R group, IR group pre-treated with pravastatin. Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 h. Treatment groups received normal saline in equal volumes prior to tourniquet release. Following 12 h reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then killed and skeletal muscle harvested for evaluation.

Results?We found that pre-treatment with pravastatin reduces the tissue oxidative damage and edema associated with skeletal muscle reperfusion injury. Skeletal muscle injury, measured by edema, leucose-questration and electrical properties were significantly lower with pravastatin pre-treatment compared to the non-treated group.

Interpretation?We feel that pravastatin pre-treatment may be a potential therapeutic intervention for skeletal muscle ischemia reperfusion injury in the clinical setting.??     

Pharmacologic intervention in ischemia-induced reperfusion injury in the skeletal muscle

This article provides a concise review on the potential causes of ischemia-induced reperfusion (I/R) injury and pharmacologic intervention in the skeletal muscle. Special emphasis is placed on the recent observation of the acute ischemic preconditioning phenomenon for prevention of I/R injury in skeletal muscle. Finally, the mechanism of ischemic preconditioning and its clinical applications for augmentation of skeletal muscle tolerance to prolonged ischemic insult are discussed. © 1993 Wiley-Liss Inc.     

Liver and skeletal muscle mitochondrial function following burn injury.

The possibility of altered mitochondrial function consequent to burn injury was investigated. Mitochondria isolated from liver or skeletal muscle of burn-injured rats (20% tbs) were compared at 3 days postburn to shams and normal controls. Mitochondrial yields were the same for all groups. ADP;O ratios were in the theoretical ranges expected and did not differ among burn, sham, and normal animals. Respiratory control ratios (RCR's) were decreased in liver mitochondria, averaging 71.7% of normal for burned animals compared to 95.8% for the sham group. The loss of respiratory control in liver mitochondria implies inefficient use of substrate chemical energy and could contribute to postburn hypermetabolism. The different response of muscle mitochondria as compared to liver suggests that alterations may be organ specific.     

Quantitative histochemical evaluation of skeletal muscle ischemia and reperfusion injury

Acute arterial obstruction to the extremities is associated with significant morbidity and mortality. The evaluation of accompanying skeletal muscle injury has thus far been indirect and imprecise. Triphenyltetrazolium chloride (TTC) is an oxidation-reduction indicator which allows for the histochemical quantitation of skeletal muscle injury. In 21 anesthetized nonheparinized adult mongrel dogs, the isolated in vivo gracilis muscle underwent 4, 6, or 8 hr of ischemia with and without reperfusion. The muscles were excised and cut into 1-cm segments, representative muscle biopsies for electron microscopy were taken, each segment was stained in 1% TTC, and the total area of staining was measured with computerized planimetry. All control muscles stained completely with a dark red color. After 4, 6, or 8 hr of ischemia, quantitative measurements of muscle staining indicative of normal tissue were present in 98 +/- 1%, 59 +/- 5%, and 23 +/- 9% of the total muscle areas, respectively. Six hours of ischemia followed by reperfusion was associated with only 36 +/- 9% of the muscle being stained. Segmental TTC staining demonstrated that reperfusion was associated with greater injury, and less TTC staining, in the proximal portion of the gracilis muscle at the site of entry of the major arterial pedicle. The distal muscle did not demonstrate increased damage with reperfusion. It is hypothesized that protection of the distal muscle from reperfusion injury may be due to an absence of reflow farther away from the artery.     

Use of dextran sulfate in tourniquet-induced skeletal muscle reperfusion injury

Background

Lower extremity ischemia–reperfusion injury (IRI)—prolonged ischemia and the subsequent restoration of circulation—may result from thrombotic occlusion, embolism, trauma, or tourniquet application in surgery. The aim of this study was to assess the effect of low-molecular-weight dextran sulfate (DXS) on skeletal muscle IRI.

Methods

Rats were subjected to 3 h of ischemia and 2 or 24 h of reperfusion. To induce ischemia the femoral artery was clamped and a tourniquet placed under the maintenance of the venous return. DXS was injected systemically 10 min before reperfusion. Muscle and lung tissue samples were analyzed for deposition of immunoglobulin M (IgM), IgG, C1q, C3b/c, fibrin, and expression of vascular endothelial-cadherin and bradykinin receptors b1 and b2.

Results

Antibody deposition in reperfused legs was reduced by DXS after 2 h (P < 0.001, IgM and IgG) and 24 h (P < 0.001, IgM), C3b/c deposition was reduced in muscle and lung tissue (P < 0.001), whereas C1q deposition was reduced only in muscle (P < 0.05). DXS reduced fibrin deposits in contralateral legs after 24 h of reperfusion but did not reduce edema in muscle and lung tissue or improve muscle viability. Bradykinin receptor b1 and vascular endothelial-cadherin expression were increased in lung tissue after 24 h of reperfusion in DXS-treated and non-treated rats but bradykinin receptor b2 was not affected by IRI.

Conclusions

In contrast to studies in myocardial infarction, DXS did not reduce IRI in this model. Neither edema formation nor viability was improved, whereas deposition of complement and coagulation components was significantly reduced. Our data suggest that skeletal muscle IRI may not be caused by the complement or coagulation alone, but the kinin system may play an important role.     

缺血预处理减轻骨骼肌缺血再灌注损伤

目的 观察缺血预处理对骨骼肌缺血再灌注损伤的保护作用。方法 选择２４只健康兔,随机等分为实验组和对照组。实验组先进行缺血预处理,再持续阻断后肢血流４ｈ;对照组直接阻断后肢血流４ｈ,制作骨骼肌缺血再灌注损伤模型。测定再灌注期血清中肌酸磷酸激酶（ＣＰＫ）和天门冬氨酸氨基转移酶（ＡＳＴ）,镜下观察骨骼肌变化。结果 实验组血清中ＣＰＫ和ＡＳＴ的含量均明显低于对照组（Ｐ〈０．０５）。实验组骨骼肌线粒体空泡变     

The effect of ischemia reperfusion injury on skeletal muscle

Ischemia reperfusion (IR) injury occurs when tissue is reperfused following a period of ischemia, and results from acute inflammation involving various mechanisms. IR injury can occur following a range of circumstances, ranging from a seemingly minor condition to major trauma. The intense inflammatory response has local as well as systemic effects because of the physiological, biochemical and immunological changes that occur during the ischemic and reperfusion periods. The sequellae of the cellular injury of IR may lead to the loss of organ or limb function, or even death. There are many factors which influence the outcome of these injuries, and it is important for clinicians to understand IR injury in order to minimize patient morbidity and mortality. In this paper, we review the pathophysiology, the effects of IR injury in skeletal muscle, and the associated clinical conditions; compartment syndrome, crush syndrome, and vascular injuries.     

Alpha-tocopherol (Vitamin E) and iloprost attenuate reperfusion injury in skeletal muscle ischemia/reperfusion injury

BACKGROUND: The aim of this study was to clarify the role of a-tocopherol (vitamin E) and iloprost on skeletal muscle ischemia/reperfusion injury. METHODS: Setting: animal research laboratory of a university hospital. Experimental design: the iliac arteries of the 24 adult Sprague-Dawley rats were clamped and 4 hours of ischemia followed by 1 hour of reperfusion was applied. In an attempt to decrease reperfusion injury, the rats were given either a-tocopherol (n=8), iloprost (n=6) and 8 rats were given normal saline and served as control group (n=8). Measures: blood pH, pO2, pCO2, HCO3, Na, K, creatine kinase (CPK), lactate dehydrogenase (LDH) values were determined at the end of the reperfusion period. Malondialdehyde (MDA), a product of lipid peroxidation, was measured in blood, muscle and lung as an indicator of free radicals. RESULTS: Blood pO2 and HCO3 levels were significantly high (p<0.05); CPK, LDH and MDA levels were significantly low (p<0.05) in both a-tocopherol and iloprost groups when compared to the control group. Similarly, the MDA levels in the gastrocnemius muscle were significantly low in both treatment groups when compared to the controls (p<0.05). There was no significant difference between groups in other parameters. CONCLUSIONS: The results suggest that, both a-tocopherol and iloprost are useful for attenuating oxidative muscle damage occurring after a period of ischemia/ reperfusion.