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1.
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. ▪ 相似文献
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. ▪ 相似文献
2.
Protective effect of the endothelin antagonist Bosentan against ischemic skeletal muscle necrosis 总被引:3,自引:0,他引:3
Kjetil Hvaal Sven R. Mathisen Aud Svindland Lars Nordsletten Sigmund Skjeldal 《Acta orthopaedica》1999,70(3):293-297
We tested the hypothesis that blocking of the endothelin system by Bosentan, a combined endothelin-A and -B receptor antagonist (Hoffmann La Roche, Basel, Switzerland), improves postischemic skeletal muscle reperfusion and reduces tissue damage.
16 Wistar rats were subjected to 3 h and 15 min hindlimb tourniquet ischemia at 27°C. Perfusion was continuously measured with Laser Doppler Flowmetry (LDF) in the anterior tibial muscle during ischemia and the first 2 h of reperfusion. Perfusion indices were calculated for each 15 min, by dividing each LDF value by the preischemic LDF value of the leg. The areas under the perfusion index curves were compared. 72h after ischemia, histomorphom-etry of necrosis and no-reflow zones, and counting of neutrophils were done in cross-sections of the muscles.
The animals were randomized into two groups. The treatment group received an injection of Bosentan 15 mg/kg 10 min before ischemia, and this dose was repeated 5 min before reperfusion of the hind-limbs. The treatment group obtained an improved reperfusion (4.48 vs. 1.72, p = 0.02). The median cross-sectional area of necrosis was smaller in the treatment group, 70% vs. 93% (p = 0.02), while neither the areas of no-reflow nor the neutrophil counts in reperfused necrotic areas were different.
This study supports the hypothesis that Bosentan seems to improve reperfusion and reduces postischemic skeletal muscle damage. 相似文献
16 Wistar rats were subjected to 3 h and 15 min hindlimb tourniquet ischemia at 27°C. Perfusion was continuously measured with Laser Doppler Flowmetry (LDF) in the anterior tibial muscle during ischemia and the first 2 h of reperfusion. Perfusion indices were calculated for each 15 min, by dividing each LDF value by the preischemic LDF value of the leg. The areas under the perfusion index curves were compared. 72h after ischemia, histomorphom-etry of necrosis and no-reflow zones, and counting of neutrophils were done in cross-sections of the muscles.
The animals were randomized into two groups. The treatment group received an injection of Bosentan 15 mg/kg 10 min before ischemia, and this dose was repeated 5 min before reperfusion of the hind-limbs. The treatment group obtained an improved reperfusion (4.48 vs. 1.72, p = 0.02). The median cross-sectional area of necrosis was smaller in the treatment group, 70% vs. 93% (p = 0.02), while neither the areas of no-reflow nor the neutrophil counts in reperfused necrotic areas were different.
This study supports the hypothesis that Bosentan seems to improve reperfusion and reduces postischemic skeletal muscle damage. 相似文献
3.
《Acta orthopaedica》2013,84(1):27-32
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.?? 相似文献
4.
《Acta orthopaedica》2013,84(5):703-707
Background and purpose Pharmacological modulation of skeletal muscle reperfusion injury after traumaassociated ischemia may improve limb salvage rates and prevent the associated systemic sequelae. Resuscitation with hypertonic saline restores the circulating volume and has favorable effects on tissue perfusion and blood pressure. We evaluated the effects of treatment with a bolus of hypertonic saline on skeletal muscle ischemia reperfusion (IR) injury and the associated end-organ injury.Methods Adult male Sprague-Dawley rats (n = 27) were randomized into 3 groups: (1) a control group, (2) an IR group treated with normal saline, and (3) an IR group treated with hypertonic saline. Bilateral hindlimb ischemia was induced by application of a rubber band proximal to the level of the greater trochanters for 2.5 h. The treatment groups received either normal saline (4 mL/kg) or hypertonic saline (4 mL/kg) prior to tourniquet release. Following 12 h of reperfusion, the tibialis anterior muscle was dissected and muscle function was assessed electrophysiologically. The animals were then killed, and skeletal muscle and lung tissue were harvested for evaluation.Results Hypertonic saline significantly attenuated skeletal muscle reperfusion injury, as shown by reduced myeloperoxidase content, wet-to-dry ratio, and electrical properties of skeletal muscle. There was a corresponding reduction in lung injury, as demonstrated by reduced myeloperoxidase content and reduced wet-to-dry ratio.Interpretation Treatment with hypertonic saline attenuates skeletal muscle ischemia reperfusion injury and its associated systemic sequelae. 相似文献
5.
Effect of superoxide dismutase plus catalase on Ca2+ transport in ischemic and reperfused skeletal muscle 总被引:3,自引:0,他引:3
K R Lee J L Cronenwett M Shlafer C Corpron G B Zelenock 《The Journal of surgical research》1987,42(1):24-32
Cytotoxic oxygen metabolites may contribute to skeletal muscle damage associated with ischemia and reperfusion. This study utilized a rat hindlimb ischemia model to investigate the effect of pretreatment with oxygen free radical scavengers superoxide dismutase (SOD) and catalase (CAT) on skeletal muscle Ca2+ uptake by sarcoplasmic reticulum (SR) in limbs subjected to periods of ischemia and reperfusion. SOD and CAT were conjugated to polyethylene glycol to prolong their half lives. Anesthetized rats (ca. 350 g) received an iv injection of either conjugated SOD (2 mg/kg) plus CAT (3.5 mg/kg) (n = 6, Treated Group) or 0.9 saline (4 ml/kg) (n = 6, Control Group) 5 min before unilateral hindlimb tourniquet ischemia of 3 hr duration. After 19 hr of reperfusion, muscle from each lower leg was excised and homogenized. Skeletal muscle SR was isolated by differential centrifugation. ATP-dependent Ca2+ uptake by the SR was then measured with dual wavelength spectrophotometry and used as an index of muscle function. Pretreatment with SOD and CAT maintained higher rates of Ca2+ uptake by SR of skeletal muscle from postischemic reperfused limbs (Treated Group 2.29 +/- 0.21 vs Control Group, 1.61 +/- 0.06 mumole Ca2+/mg protein/min). These results implicate cytotoxic oxygen metabolites in the pathogenesis of ischemic reperfusion skeletal muscle injury. 相似文献
6.
K Hvaal S R Mathisen A Svindland L Nordsletten S Skjeldal 《Acta orthopaedica Scandinavica》1999,70(3):293-297
We tested the hypothesis that blocking of the endothelin system by Bosentan, a combined endothelin-A and -B receptor antagonist (Hoffmann La Roche, Basel, Switzerland), improves postischemic skeletal muscle reperfusion and reduces tissue damage. 16 Wistar rats were subjected to 3 h and 15 min hindlimb tourniquet ischemia at 27 degrees C. Perfusion was continuously measured with Laser Doppler Flowmetry (LDF) in the anterior tibial muscle during ischemia and the first 2 h of reperfusion. Perfusion indices were calculated for each 15 min, by dividing each LDF value by the preischemic LDF value of the leg. The areas under the perfusion index curves were compared. 72 h after ischemia, histomorphometry of necrosis and no-reflow zones, and counting of neutrophils were done in cross-sections of the muscles. The animals were randomized into two groups. The treatment group received an injection of Bosentan 15 mg/kg 10 min before ischemia, and this dose was repeated 5 min before reperfusion of the hindlimbs. The treatment group obtained an improved reperfusion (4.48 vs. 1.72, p = 0.02). The median cross-sectional area of necrosis was smaller in the treatment group, 70% vs. 93% (p = 0.02), while neither the areas of no-reflow nor the neutrophil counts in reperfused necrotic areas were different. This study supports the hypothesis that Bosentan seems to improve reperfusion and reduces postischemic skeletal muscle damage. 相似文献
7.
The purpose of this study was to evaluate the effectiveness of deferoxamine in preventing detrimental microvascular changes in ischemically damaged skeletal muscle during the initial reperfusion stage. Sprague-Dawley rats were given saline or deferoxamine (25 or 50 mg/kg) intravenously just prior to release of an air tourniquet placed around one hindlimb for 4 h. The limb was allowed to reperfuse for 2 h. Vascular leakage of plasma protein was assayed by determining the amount of 131I-labeled serum albumin that was given intravenously 30 min prior to release of the tourniquet. The wet and dry weights of the gastrocnemius and tibialis anterior muscles and the 131I activity were evaluated in both ischemic and nonischemic limbs. Although vascular permeability and edema increased markedly in both muscles in the ischemic limbs, there were no significant differences between the saline or either treatment groups. The lack of effect of deferoxamine in this initial report suggests that skeletal muscle may differ from other tissues in the early reperfusion stage. 相似文献
8.
Comparison of histopathologic effects of carnitine and ascorbic acid on reperfusion injury. 总被引:3,自引:0,他引:3
H Akar A Sara? C Konuralp L Yildiz F Kolbakir 《European journal of cardio-thoracic surgery》2001,19(4):500-506
OBJECTIVE: Reperfusion injury can be seen after acute arterial occlusion, acute myocardial infarctus and during open heart surgery and vascular surgery. Protective effects of ascorbic acid and carnitine on reperfusion damage were tested and compared using histopathologic examination on ischemia model in the rabbit hind limb. METHODS: Four groups (each containing ten animals) were used. In group I (G1), only anesthesia was administered and a biopsy was taken from the soleus muscle after 6 h. In group II (G2), group III (G3), and group IV (G4), after induction of anesthesia, arterial blood circulation of right posterior extremity was blocked by a tourniquet proximally. After four hours of ischemia, just before releasing of tourniquet, physiologic saline solution, sodium ascorbate (Redoxan) and L-carnitine (Carnitine) were administered intravenously to G2, G3 and G4, respectively. Following 2 h of reperfusion, biopsies were taken from soleus muscles. All of the biopsy slides were observed under the light microscope from the aspect of six different histopathologic criteria (loss of striation, nuclear centralisation, formation of ring and/or splitting, changing on diameters of muscle fibers, necrosis and minimal fibrosis) of ischemic muscle. RESULTS: Ischemic change criteria were seen less frequency in both vitamin C and carnitine groups compared to the control and placebo groups. However, this protective effect was statistically significant only for the aspect of segmental necrosis, centralization of nuclei and diameter change parameters in G3 and in G4. When G3 and G4 were compared, the differences on protective effects were significant only from the aspect of fibrosis (P<0.001) and changing on diameter of the fibers (P<0.001). CONCLUSIONS: Both sodium ascorbate and carnitine are effective on reducing the reperfusion injury in skeletal muscle. But when we compared these two agents to each other, we found that carnitine seems a little more protective on our experimental model. 相似文献
9.
《Journal of investigative surgery》2013,26(4):375-381
The purpose of this study was to evaluate the effectiveness of deferoxamine in preventing detrimental microvascular changes in ischemically damaged skeletal muscle during the initial reperfusion stage. Sprague-Dawley rats were given saline or deferoxamine (25 or 50 mg/kg) intravenously just prior to release of an air tourniquet placed around one hindlimb for 4 h. The limb was allowed to reperfuse for 2 h. Vascular leakage of plasma protein was assayed by determining the amount of 131I-labeled serum albumin that was given intravenously 30 min prior to release of the tourniquet. The wet and dry weights of the gastrocnemius and tibialis anterior muscles and the 131I activity were evaluated in both ischemic and nonischemic limbs. Although vascular permeability and edema increased markedly in both muscles in the ischemic limbs, there were no significant differences between the saline or either treatment groups. The lack of effect of deferoxamine in this initial report suggests that skeletal muscle may differ from other tissues in the early reperfusion stage. 相似文献
10.
Introduction Ischemia-reperfusion (IR) injury is a common surgical event, with tourniquet use being a recognized cause in orthopedic surgery. Preconditioning is a highly evolutionarily conserved endogenous protective mechanism, but finding a clinically safe, acceptable method of induction has proven difficult. Glutamine, a known inducer of the heat shock protein response, offers pharmacological modulation of injury through clinically acceptable preconditioning. Our aim was to test the hypothesis that glutamine preconditioning protects against tourniquet-induced regional and remote IR injury in a rodent model.
Animals and methods 40 adult male Sprague-Dawley rats were randomized into 4 groups: control, IR injury, normal saline-pretreated and IR injury, and glutamine-pretreated and IR injury. Pretreated groups received either normal saline or glutamine by intravenous bolus 24 h before injury. A bilateral hindlimb tourniquet model was used. Blood samples were analyzed, bronchioalveolar lavage (BAL) performed, and skeletal muscle and lung harvested for evaluation.
Results The glutamine-pretreated group showed significantly lower muscle myeloperoxidase (MPO) content and creatine kinase levels than the untreated or salinepretreated injury groups. Lung tissue showed reduced MPO content and a significantly reduced neutrophil count by BAL fluid microscopy.
Interpretation These data suggest that preconditioning with glutamine offers local and distant organ protection in the setting of tourniquet-induced IR injury. 相似文献
Animals and methods 40 adult male Sprague-Dawley rats were randomized into 4 groups: control, IR injury, normal saline-pretreated and IR injury, and glutamine-pretreated and IR injury. Pretreated groups received either normal saline or glutamine by intravenous bolus 24 h before injury. A bilateral hindlimb tourniquet model was used. Blood samples were analyzed, bronchioalveolar lavage (BAL) performed, and skeletal muscle and lung harvested for evaluation.
Results The glutamine-pretreated group showed significantly lower muscle myeloperoxidase (MPO) content and creatine kinase levels than the untreated or salinepretreated injury groups. Lung tissue showed reduced MPO content and a significantly reduced neutrophil count by BAL fluid microscopy.
Interpretation These data suggest that preconditioning with glutamine offers local and distant organ protection in the setting of tourniquet-induced IR injury. 相似文献
11.
Wakai A Winter DC Street JT O'Sullivan RG Wang JH Redmond HP 《The Journal of surgical research》2001,99(2):311-315
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. 相似文献
12.
Oxygen-derived free radical scavengers and skeletal muscle ischemic/reperfusion injury 总被引:1,自引:0,他引:1
Total injury in ischemic skeletal muscle is a function of ischemic damage and reperfusion injury. In an attempt to decrease reperfusion injury, we gave the oxygen-derived free radical scavengers allopurinol, superoxide dismutase, or mannitol during reperfusion of canine gracilis muscle made ischemic for 4 hours. We measured muscle O2 consumption (MVO2), and tissue calcium, water, and adenosine triphosphatase (ATP) before ischemia, after ischemia, and at 5 minutes and 60 minutes of reperfusion. The results at 60 minutes showed no improvement in MVO2 or ATP. In fact, ATP was significantly depressed with allopurinol and superoxide dismutase treatment, and tissue edema did not decrease in any of the groups. We conclude that the simple addition of oxygen-derived free radical scavengers during the initial reperfusion of totally ischemic skeletal muscle does not attenuate reperfusion injury. 相似文献
13.
Heather-Marie P. Wilson Robert E. Welikson Jun Luo Thomas J. Kean Baohong Cao James E. Dennis Margaret D. Allen 《Clinical orthopaedics and related research》2015,473(9):2908-2919
Background
Extremity trauma is the most common injury seen in combat hospitals as well as in civilian trauma centers. Major skeletal muscle injuries that are complicated by ischemia often result in substantial muscle loss, residual disability, or even amputation, yet few treatment options are available. A therapy that would increase skeletal muscle tolerance to hypoxic damage could reduce acute myocyte loss and enhance preservation of muscle mass in these situations.Questions/purposes
In these experiments, we investigated (1) whether cobalt protoporphyrin (CoPP), a pharmacologic inducer of cytoprotective heme oxygenase-1 (HO-1), would upregulate HO-1 expression and activity in skeletal muscle, tested in muscle-derived stem cells (MDSCs); and (2) whether CoPP exposure would protect MDSCs from cell death during in vitro hypoxia/reoxygenation. Then, using an in vivo mouse model of hindlimb ischemia/reperfusion injury, we examined (3) whether CoPP pharmacotherapy would reduce skeletal muscle damage when delivered after injury; and (4) whether it would alter the host inflammatory response to injury.Methods
MDSCs were exposed in vitro to a single dose of 25 μΜ CoPP and harvested over 24 to 96 hours, assessing HO-1 protein expression by Western blot densitometry and HO-1 enzyme activity by cGMP levels. To generate hypoxia/reoxygenation stress, MDSCs were treated in vitro with phosphate-buffered saline (vehicle), CoPP, or CoPP plus an HO-1 inhibitor, tin protoporphyrin (SnPP), and then subjected to 5 hours of hypoxia (< 0.5% O2) followed by 24 hours of reoxygenation and evaluated for apoptosis. In vivo, hindlimb ischemia/reperfusion injury was produced in mice by unilateral 2-hour tourniquet application followed by 24 hours of reperfusion. In three postinjury treatment groups (n = 7 mice/group), CoPP was administered intraperitoneally during ischemia, at the onset of reperfusion, or 1 hour later. Two control groups of mice with the same injury received phosphate-buffered saline (vehicle) or the HO-1 inhibitor, SnPP. Myocyte damage in the gastrocnemius and tibialis anterior muscles was determined by uptake of intraperitoneally delivered Evans blue dye (EBD), quantified by image analysis. On serial sections, inflammation was gauged by the mean myeloperoxidase staining intensity per unit area over the entirety of each muscle.Results
In MDSCs, a single exposure to CoPP increased HO-1 protein expression and enzyme activity, both of which were sustained for 96 hours. CoPP treatment of MDSCs reduced apoptotic cell populations by 55% after in vitro hypoxia/reoxygenation injury (from a mean of 57.3% apoptotic cells in vehicle-treated controls to 25.7% in CoPP-treated cells, mean difference 31.6%; confidence interval [CI], 28.1–35.0; p < 0.001). In the hindlimb ischemia/reperfusion model, CoPP delivered during ischemia produced a 38% reduction in myocyte damage in the gastrocnemius muscle (from 86.4% ± 7% EBD+ myofibers in vehicle-treated, injured controls to 53.2% EBD+ in CoPP-treated muscle, mean difference 33.2%; 95% CI, 18.3, 48.4; p < 0.001). A 30% reduction in injury to the gastrocnemius was seen with drug delivery at the onset of reperfusion (to 60.6% ± 13% EBD+ with CoPP treatment, mean difference 25.8%; CI, 12.2–39.4; p < 0.001). In the tibialis anterior, however, myocyte damage was decreased only when CoPP was given at the onset of reperfusion, resulting in a 27% reduction in injury (from 78.8% ± 8% EBD+ myofibers in injured controls to 58.3% ± 14% with CoPP treatment, mean difference 20.5%; CI, 6.1–35.0; p = 0.004). Delaying CoPP delivery until 1 hour after tourniquet release obviated the protective effect in both muscles. Mean MPO staining intensity per unit area, indicating the host inflammatory response, decreased by 27–34% across both the gastrocnemius and tibialis anterior muscles when CoPP was given either during ischemia or at the time of reperfusion. Delaying drug delivery until 1 hour after the start of reperfusion abrogated this antiinflammatory effect.Conclusions
CoPP can decrease skeletal muscle damage when given early in the course of ischemia/reperfusion injury and also provide protection for regenerative stem cell populations.Clinical Relevance
Pharmacotherapy with HO-1 inducers, delivered in the field, on hospital arrival, or during trauma surgery, may improve preservation of muscle mass and muscle-inherent stem cells after severe ischemic limb injury.Electronic supplementary material
The online version of this article (doi:10.1007/s11999-015-4332-8) contains supplementary material, which is available to authorized users. 相似文献14.
J.P. Dillon A.J. Laing R.C. Cahill G.C. O’Brien J.H. Wang A.J. McGuiness H.P. Redmond 《The Journal of surgical research》2003,114(2):248
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. 相似文献
15.
Robert K Eastlack Eli R Groppo Alan R Hargens Robert A Pedowitz 《Journal of orthopaedic research》2004,22(4):918-923
The primary purpose of this study was to evaluate ischemic-preconditioning (IPC) as a means of improving tolerance to ischemia-reperfusion (IR) stress on neuromuscular function. A secondary objective was to isolate the area of injury within the neuromuscular unit responsible for contractile dysfunction after IR injury. Twenty-eight male rabbits were randomly assigned to four groups (sham, IPC only, sustained ischemia only, IPC and sustained ischemia). The IPC protocol consisted of three cycles of 10 min of tourniquet-induced ischemia (125 mmHg) followed by 10 min of reperfusion. Sustained ischemia was induced by 350 mmHg external compression for 2 h. Peak tetanic tension of the tibialis anterior (TA) muscle was evaluated 48 h after the tourniquet protocol by both peroneal nerve and direct muscle stimulation, with and without pharmacologic neuromuscular junction blockade. Animals subjected to combined IPC and sustained ischemia had an equivalent loss of contractile force to those undergoing sustained ischemia alone. Two hours of tourniquet-induced ischemia resulted in marked dysfunction of the TA neuromuscular unit when evaluated by peroneal nerve stimulation (p < 0.0001). Isolation of the TA muscle from the peroneal nerve with direct muscle stimulation and neuromuscular junction blockade preserved muscle function after 3 h of ischemia. In our model, these results clearly demonstrate that IPC provides no significant protective effect from IR injury to either nerve or muscle function in our model. In addition, nerve or neuromuscular junction injury, rather than muscle damage, is identified as primarily responsible for IR-related muscle dysfunction. 相似文献
16.
To study the effect of ischemia reperfusion injury on microvascular reactivity and tissue metabolism in skeletal muscle, a Sprague-Dawley rat cremaster muscle was prepared as a tourniquet ischemia model and subjected to 2 hr ischemia followed by 1 hr reperfusion to simulate the timing of ischemia during microvascular surgery. The dose-response curve of arteriolar reactivity to norepinephrine, lipid peroxidation, and ultrastructure of capillaries was determined in both the control and postischemic reperfusion stages. Judging from the results, we summarize our observations as follows: (1) Postischemic reperfusion significantly increased arteriolar reactivity to norepinephrine, in which the EC50 for vasoconstriction decreased in all three orders of arterioles. These results suggest that reperfusion could have impaired the vasodilation control mechanism, possibly being endothelium dependent. (2) Lipid peroxidation increased sixfold in the reperfusion group, suggesting that oxygen free radicals have produced significant tissue damage under the created conditions. (3) Significant endothelial damage in the capillaries shown by electron microscope observation supports these studies, indicating that ischemia/reperfusion in clinically transplanted skeletal muscles could cause significant damage to the tissue microcirculation both physiologically and metabolically. © 1995 Wiley-Liss, Inc. 相似文献
17.
Ostman B Michaelsson K Rahme H Hillered L 《Clinical orthopaedics and related research》2004,(418):260-265
Microdialysis conceivably enables longitudinal and simultaneous investigation of several metabolites by repeated measurements in skeletal muscle. We used and evaluated microdialysis as an in vivo method to characterize the time-course and relative kinetics of pyruvate, glucose, lactate, glycerol, hypoxanthine, uric acid, and urea, in skeletal muscles, exposed to ischemia and reperfusion, in eight patients having arthroscopic-assisted anterior cruciate ligament reconstruction. A dialysis probe was implanted before surgery in the rectus femoris muscle. Dialysate samples were collected at 10-minute intervals at a flow rate of 1 microL/minute until 2 hours after tourniquet deflation. Ninety minutes of ischemia resulted in accumulation of lactate (234% +/- 38%), hypoxanthine (582% +/- 166%), and glycerol (146% +/- 46%), consumption of glucose (54% +/- 9%) and pyruvate (16% +/- 44%), and a slight decrease of urea (78% +/- 11%) compared with baseline (100%). Uric acid was unchanged (95% +/- 12%). Within 90 minutes after tourniquet deflation the concentrations were virtually normalized for all measured metabolites, suggesting that the duration of ischemia was well tolerated by the patients. The results indicate that the use of microdialysis for monitoring energy metabolic events during orthopaedic surgery that requires ischemia and reperfusion is feasible and safe. 相似文献
18.
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. 相似文献
19.
Kauvar DS Baer DG Dubick MA Walters TJ 《Journal of the American College of Surgeons》2006,202(6):888-896
BACKGROUND: Severe extremity wounds with vascular injury are common in military trauma, and tourniquets are commonly used for hemorrhage control. The complications of tourniquet use in the setting of trauma are not well studied. This study investigated the combined effect of hemorrhagic shock and fluid resuscitation with Hextend (HX; BioTime, Inc) or lactated Ringer's (LR) on skeletal muscle subjected to tourniquet-induced ischemia-reperfusion injury. STUDY DESIGN: Thirty male Sprague-Dawley rats underwent 33% arterial hemorrhage followed by 3 hours of tourniquet application. Before reperfusion, 10 animals each were resuscitated with lactated Ringer's (3 times shed volume) or HX (shed volume). Ten control animals received no resuscitation. Rats were euthanized 2 hours after tourniquet release and the tibialis anterior and medial gastrocnemius muscles were examined for edema (muscle wet weight) and viability (nitroblue tetrazolium reduction). Contralateral muscles served as controls for each animal, with results expressed as the ratio of the tourniquet limb to contralateral limb values. RESULTS: The tibialis anterior and medial gastrocnemius muscles in all groups experienced edema, with all weight ratios greater than one. Resuscitation with HX resulted in significantly (p < 0.05) greater edema than did no resuscitation in both muscles and greater edema than with lactated Ringer's in the medial gastrocnemius. All groups experienced a loss of viability as well, with nitroblue tetrazolium reduction ratios less than one. Resuscitation with HX resulted in significantly less viability loss than did no resuscitation in the medial gastrocnemius. No significant differences in viability were seen in the tibialis anterior. CONCLUSIONS: Resuscitation with HX or lactated Ringer's does not adversely affect muscle viability in ischemia-reperfusion injury. HX may be a better clinical choice when skeletal muscle ischemia-reperfusion injury is a risk, despite greater edema. 相似文献
20.
The protective effects of allopurinol and superoxide dismutase-polyethylene glycol on ischemic and reperfusion-induced cochlear damage 总被引:6,自引:0,他引:6
M D Seidman W S Quirk A L Nuttall V G Schweitzer 《Otolaryngology--head and neck surgery》1991,105(3):457-463
The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions. 相似文献