Limb Ischemia-reperfusion Injury Research Articles

Apocynin and dimethyl sulfoxide synergistically protect against ischemia-reperfusion injury in a rat hind limb ischemia-reperfusion model

Acute ischemia and reperfusion in extremities ignite a complicated inflammatory cycle and lead to damage in the extremities and target tissues. Rats were randomly divided into four groups. Each experimental group contained eight rats. Group 1 was the sham surgery group. Group 2 was the control I/R group with intraperitoneal serum physiologic (SP) treatment. Group 3 was the I/R group with vehicle treatment (8% DMSO). Group 4 was the I/R group with 20 mg/kg apocynin (vehicle 8% DMSO). The potential protective effects of apocynin and vehicle (DMSO) in the rat hind limb ischemia-reperfusion model were evaluated by measuring the levels of plasma pro-inflammatory cytokines and oxidative stress markers in muscle tissue. The results revealed that both apocynin and vehicle (DMSO) alone increased the antioxidative capacity of ischemic tissue and reduced the levels of plasma proinflammatory cytokines compared to control I/R group. There was a statically more significant effect in the apocynin (vehicle 8% DMSO)-treated group 4. We observed that apocynin and DMSO synergistically prevent the I/R injury in rat hind limb ischemia-reperfusion injury model and meaningfully decrease the inflammatory parameters. Level of Evidence: Not ratable.

Effect of Different Doses of Pregabalin on Erythrocyte Deformability in Rats with Lower Limb Ischemia Reperfusion Injury

Effect of Different Doses of Pregabalin on Erythrocyte Deformability in Rats with Lower Limb Ischemia Reperfusion Injury

Pretreatment with Fish Oil-Based Lipid Emulsion Modulates Muscle Leukocyte Chemotaxis in Murine Model of Sublethal Lower Limb Ischemia

This study investigated the effects of a fish oil- (FO-) based lipid emulsion on muscle leukocyte chemotaxis and inflammatory responses in a murine model of limb ischemia-reperfusion (IR) injury. Mice were assigned randomly to 1 sham (sham) group, 2 ischemic groups, and 2 IR groups. The sham group did not undergo the ischemic procedure. The mice assigned to the ischemic or IR groups were pretreated intraperitoneally with either saline or FO-based lipid emulsion for 3 consecutive days. The IR procedure was induced by applying a 4.5 oz orthodontic rubber band to the left thigh above the greater trochanter for 120 min and then cutting the band to allow reperfusion. The ischemic groups were sacrificed immediately while the IR groups were sacrificed 24 h after reperfusion. Blood, IR-injured gastrocnemius, and lung tissues were collected for analysis. The results showed that FO pretreatment suppressed the local and systemic expression of several IR-induced proinflammatory mediators. Also, the FO-pretreated group had lower blood Ly6ChiCCR2hi monocyte percentage and muscle M1/M2 ratio than the saline group at 24 h after reperfusion. These findings suggest that FO pretreatment may have a protective role in limb IR injury by modulating the expression of proinflammatory mediators and regulating the polarization of macrophage.

Effects of intravenous ibuprofen and lornoxicam on erythrocyte deformability in rats undergoing hind limb ischemia reperfusion injury.

Acute hind limb ischemia reperfusion (I/R) injury is a common consequence of abdominal aorta cross‑clamping during aortic surgery. Erythrocyte deformability is affected by I/R process and may lead to increased tissue and organ injury. Lornoxicam and intravenous ibuprofen are becoming commonly used as non-steroidal anti-inflammatory drugs (NSAID) for postoperative analgesia. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg iv) and intravenous ibuprofen (30 mg/kg iv) on erythrocyte deformability in I/R model in rats. Four study groups, each containing 6 Wistar rats were created. Laparotomy was performed in all groups under general anesthesia with ketamine and xylazine. In all groups except sham group, ischemia and reperfusion were achieved by clamping and declamping the infrarenal abdominal aorta for 120 minutes. Rats in Group IR+L received intravenous infusion of lornoxicam (2 mg/kg) while rats in Group IR+I received intravenous infusion of ibubrofen (30 mg/kg) following 2 hours of ischemic period. At the end of reperfusion period, erythrocyte packs were prepared from heparinized blood samples. Erythrocyte suspensions with hematocrit at a concentration of 5% in a phosphate‑buffered saline (PBS) were used in order to perform deformability measurements. The value of p<0.05 was considered statistically significant. Relative resistance has increased in ischemia reperfusion group when compared to control group (p < 0.0001). Lornoxicam or ibuprofen intravenous treatments did not change the erythrocyte deformability during ischemia reperfusion period in rats (p=0.851, p=0.690). Intravenous ibuprofen or lornoxicam administrations during ischemia reperfusion period in rats have no negative effect on erythrocyte deformability. The findings of the study should be supported with more detailed and extensive clinical/experimental studies in the future (Fig. 1, Ref. 18).

Administration of FTY720 during Tourniquet-Induced Limb Ischemia Reperfusion Injury Attenuates Systemic Inflammation.

Acute ischemia-reperfusion injury (IRI) of the extremities leads to local and systemic inflammatory changes which can hinder limb function and can be life threatening. This study examined whether the administration of the T-cell sequestration agent, FTY720, following hind limb tourniquet-induced skeletal muscle IRI in a rat model would attenuate systemic inflammation and multiple end organ injury. Sprague-Dawley rats were subjected to 1 hr of ischemia via application of a rubber band tourniquet. Animals were randomized to receive an intravenous bolus of either vehicle control or FTY720 15 min after band placement. Rats (n = 10/time point) were euthanized at 6, 24, and 72 hr post-IRI. Peripheral blood as well as lung, liver, kidney, and ischemic muscle tissue was analyzed and compared between groups. FTY720 treatment markedly decreased the number of peripheral blood T cells (p < 0.05) resulting in a decreased systemic inflammatory response and lower serum creatinine levels and had a modest but significant effect in decreasing the transcription of injury-associated target genes in multiple end organs. These findings suggest that early intervention with FTY720 may benefit the treatment of IRI of the limb. Further preclinical studies are necessary to characterize the short-term and long-term beneficial effects of FTY720 following tourniquet-induced IRI.

Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats

ABSTRACTAim: The aim of this study was to investigate whether dexmedetomidine – administered before ischemia – has protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats.Material and Methods: After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DM-C. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed.Results: Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group. Also, GV, VVH, and THC levels in the dexmedetomidine-treated group (Group DM-I/R-D) were found significantly decreased when compared with the Group DM-I/R.Conclusion: We found that dexmedetomidine − 100 μg/kg intraperitoneally – administered 30 minutes before ischemia in diabetic rats ameliorates lipid peroxidation, oxidative stress, and I-R-related renal injury. We suggest that dexmedetomidine administration in diabetic rats before I/R has renoprotective effects.

Hyperbaric oxygen therapy in the treatment of 1 patient with limb ischemia reperfusion injury after the treatment of double lower limb arterial embolism

Hyperbaric oxygen therapy in the treatment of 1 patient with limb ischemia reperfusion injury after the treatment of double lower limb arterial embolism

Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection.

Aims and ObjectivesAcute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction.MethodsMale Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2μg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected.ResultsSystemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion.ConclusionThe results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.

Effects of sinomenine on hind limb ischemia-reperfusion injury and expression of Bcl-2 and Bax in skeletal muscle cells of rats

Objective To investigate the effects of sinomenine on hind limb ischemia-reperfusion (I/R) injury and expression of Bcl-2 and Bax in skeletal muscle cells of rats. Methods Fifty-four healthy adult male Wistar rats, aged 6-8 weeks, weighing 180-220 g, were divided into 3 groups (n=18 each) using a random number table: sham operation group (group S), group I/R and sinomenine group (group SIN). The rats were subjected to 4 h of ischemia on the proximal part of the right hind limb using elastic rubber bands followed by reperfusion in I/R and SIN groups.Sinomenine 60 mg/kg was injected intraperitoneally at 30 min before reperfusion in group SIN, and the equal volume of normal saline was given instead of sinomenine at 30 min before reperfusion in S and I/R groups.Immediately after onset of reperfusion and at 4 and 24 h of reperfusion, blood samples were collected from the cardiac apex to measure the concentrations of serum lactate dehydrogenase (LDH) and creatine kinase (CK). The animals were sacrificed immediately after blood sampling, and the gastrocnemius specimens of the hind limb were immediately removed for determination of the wet to dry weight ratio (W/D ratio) and expression of Bcl-2 and Bax in gastrocnemius cells (by immunohistochemistry) and for examination of the pathological changes after haematoxylin and eosin staining.The Bcl-2/Bax ratio was calculated. Results Compared with group S, the gastrocnemius W/D ratio and concentrations of serum LDH and CK were significantly increased, the expression of Bcl-2 was significantly down-regulated, the expression of Bax was significantly up-regulated, and the Bcl-2/Bax ratio was significantly decreased in I/R and SIN groups (P<0.05). Compared with group I/R, the gastrocnemius W/D ratio and concentrations of serum LDH and CK were significantly decreased, the expression of Bcl-2 was significantly up-regulated, the expression of Bax was significantly down-regulated, and the Bcl-2/Bax ratio was significantly increased in group SIN (P<0.05). The pathological changes of the gastrocnemius were significantly attenuated in group SIN as compared with group I/R. Conclusion Sinomenine can attenuate hind limb I/R injury, and the mechanism may be related to maintenance of the balance between Bcl-2 and Bax and to inhibition of apoptosis in skeletal muscle cells of rats. Key words: Sinomenium; Reperfusion injury; Extremities; Proto-oncogene proteins c-bcl-2; bcl-2-associated X protein

Effect of picroside II on erythrocyte deformability and lipid peroxidation in rats subjected to hind limb ischemia reperfusion injury.

BackgroundIschemia reperfusion injury (I/R) in hind limb is a frequent and important clinical phenomenon. Many structural and functional damages are observed in cells and tissues in these kinds of injuries. In this study, we aimed to evaluate the effect of picroside II on lipid peroxidation and erythrocyte deformability during I/R in rats.MethodsRats were randomly divided into four groups – each containing six animals (sham, I/R, sham + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R groups. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg·kg−1) was administered intraperitoneally to the animals in the appropriate groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized by intraperitoneal administration of ketamine (100 mg·kg−1) and taking blood from the abdominal aorta. Erythrocytes were extracted from heparinized complete blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the filtration system and the changes in pressure were measured to investigate the role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and erythrocyte deformability index.ResultsDeformability index was significantly increased in the I/R group compared to groups sham, sham + picroside-II, and I/R + picroside-II (P<0.0001, P<0.0001, and P=0.007). Malondialdehyde (MDA) and NO levels were evaluated. MDA level and NO activity were also higher in the I/R group than in the other groups. Picroside II treatment before hind limb I/R prevented these changes.ConclusionThese results support that deformability of erythrocytes is decreased in I/R injury and picroside II plays a critical role to prevent these alterations. Further experimental and clinical studies are needed to evaluate and clarify the molecular mechanisms of action and clinical importance of these findings.

Effect of DNase I treatment and neutrophil depletion on acute limb ischemia-reperfusion injury in mice

Extracellular traps (ETs) consisting of DNA-protein complexes formed after tissue injury contribute to the inflammatory and thrombosis cascades, thereby exacerbating injury. Exogenous DNase I has been suggested as a therapeutic strategy to limit injury in the brain and myocardium. These studies were designed to evaluate the effects of exogenous DNase I treatment on skeletal muscle injury after acute hindlimb ischemia-reperfusion (IR) injury in mice and to determine whether neutrophils are a major source of ETs in postischemic muscle tissue. C57BL6 mice were subjected to 1.5hours of tourniquet ischemia and 24hours of reperfusion with and without human recombinant DNase I treatment. A separate set of mice was subjected to neutrophil depletion (ND), followed by the same intervals of IR. Laser Doppler imaging and tissue harvesting were done at 24hours for assessment of limb perfusion, muscle fiber injury, adenosine triphosphate (ATP) level, markers of inflammation, thrombosis, and formation of ETs. DNase I treatment significantly reduced detection of ETs in postischemic muscle but did not alter skeletal muscle fiber injury, levels of proinflammatory molecules, or ATP level. DNase I treatment did enhance postischemic hindlimb perfusion, decreased infiltrating inflammatory cells, and reduced the expression of thrombin-antithrombin III. ND resulted in a significant yet small reduction in ETs in the postischemic muscle. ND did not alter skeletal muscle fiber injury, hindlimb perfusion, or ATP levels. These data suggest that neither DNase I treatment nor ND was protective against IR injury, even though both decreased detection of ETs in skeletal muscle after IR. Neutrophils are not the only source of ETs after IR.

HIF-P4H-2 deficiency protects against skeletal muscle ischemia-reperfusion injury.

We show here that mice hypomorphic for hypoxia-inducible factor prolyl 4-hydroxylase-2 (HIF-P4H-2) (Hif-p4h-2 (gt/gt)), the main regulator of the stability of the HIFα subunits, have normoxic stabilization of HIF-1α and HIF-2α in their skeletal muscles. The size of the capillaries, but not their number, was increased in the skeletal muscles of the Hif-p4h-2 (gt/gt) mice, whereas the amount of glycogen was reduced. The expression levels of genes for glycolytic enzymes, glycogen branching enzyme 1 and monocarboxylate transporter 4, were increased in the Hif-p4h-2 (gt/gt) skeletal muscles, whereas no significant increases were detected in the levels of any vasculature-influencing factor studied. Serum lactate levels of the Hif-p4h-2 (gt/gt) mice recovered faster than those of the wild type following exercise. The Hif-p4h-2 (gt/gt) mice had elevated hepatic phosphoenolpyruvate carboxykinase activity, which may have contributed to the faster clearance of lactate. The Hif-p4h-2 (gt/gt) mice had smaller infarct size following limb ischemia-reperfusion injury. The increased capillary size correlated with the reduced infarct size. Following ischemia-reperfusion, glycogen content and ATP/ADP and CrP/Cr levels of the skeletal muscle of the Hif-p4h-2 (gt/gt) mice were higher than in the wild type. The higher glycogen content correlated with increased expression of phosphofructokinase messenger RNA (mRNA) and the increased ATP/ADP and CrP/Cr levels with reduced apoptosis, suggesting that HIF-P4H-2 deficiency supported energy metabolism during ischemia-reperfusion and protection against injury. Key messages: HIF-P4H-2 deficiency protects skeletal muscle from ischemia-reperfusion injury. The mechanisms involved are mediated via normoxic HIF-1α and HIF-2α stabilization. HIF-P4H-2 deficiency increases capillary size but not number. HIF-P4H-2 deficiency maintains energy metabolism during ischemia-reperfusion.

Fresh frozen plasma reduces edema in skeletal muscle following combined limb ischemia-reperfusion injury and hemorrhagic shock in rats

Exsanguination from extremity vascular injuries is the most common potentially survivable injury on the battlefield. Advances in treatment have dramatically improved survival, increasing the need to address associated morbidities including ischemia-reperfusion injury and extremity compartment syndrome. Despite advances, hemorrhagic shock (HS) requiring fluid resuscitation is common. Plasma-based resuscitation for the treatment of HS has been shown to reduce edema and injury in tissues other than muscle. The objective of this study was to determine if fresh frozen plasma (FFP) resuscitation offered protection in a rat model of combined HS and skeletal muscle ischemia-reperfusion injury. Anesthetized Sprague-Dawley rats underwent 37.5% arterial hemorrhage, producing HS, followed by 3 hours of tourniquet application. Animals were not resuscitated or resuscitated with either FFP (equal to the shed blood volume) or lactated Ringer's solution (three times shed volume) after 30 minutes of ischemia. They were euthanized 24 hours later, and their muscles were analyzed for edema (wet weight-dry weight). Routine histology was performed on muscle cross-sections stained with hematoxylin and eosin and graded using a semiquantitative grading system. All animals developed HS; the mortality rate was 50% in no resuscitation rats. FFP reduced edema by 13% (p = 0.02) compared with lactated Ringer's solution. Pathology scores were not different between treatment groups. FFP resuscitation reduces edema following muscle injury, decreasing the risk of developing extremity compartment syndrome.

Inhibition of reactive oxygen species downregulates the MAPK pathway in rat spinal cord after limb ischemia reperfusion injury

IntroductionWe examined the activity of mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in rats pinal cord after hind limb ischemia reperfusion (IR) and analyzed the role of reactive oxygen species (ROS) as mediators of MAPK signaling under these conditions. MethodsIn experiment 1, hind limb IR rats were treated intraperitoneally with one of following agents at 30 min before reperfusion: allopurinol (4, 40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N-nitro-l-arginine methyl ester (l-NAME, 10 mg/kg), or SOD (4000 U/kg) + l-NAME (10 mg/kg). In experiment 2, 5,10,15,20-tetrakis (N-methyl-4′-pyridyl) porphyrinato iron (III) (FeTMPyP) was administered intraperitoneally (1, 3, or 10 mg/kg) 30 min before reperfusion. After 3 d reperfusion period, the spinal cord (L4–6) was harvested to investigate MAPK signaling activity. ResultsIn experiment 1, p-ERK and p-JNK levels were significantly higher in the IR group than sham group. Administration of allopurinol, SOD, l-NAME, or SOD + l-NAME significantly reduced the IR-induced increase in p-ERK and p-JNK levels. There were no significant differences in p-p38 levels. In experiment 2, FeTMPyP significantly reduced the IR-induced increase in p-ERK and p-JNK levels in a dose-dependent manner. ConclusionsActivation of ERK and JNK in the spinal cord was induced by hind limb IR and was not accompanied by p38 activation. IR-induced MAPK phosphorylation was reduced by inhibition of superoxide, nitric oxide, and peroxynitrite, indicating that ROS produced by hind limb IR mediate the activation of these signaling pathways in the spinal cord, potentially affecting distant organs.

Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury.

This study investigated the effects of intravenous glutamine (GLN) administration on the expression of adhesion molecules and inflammatory mediators in a mice model of hind limb ischemia/reperfusion (IR) injury. There were 3 IR groups and 1 normal control (NC) group. The NC group did not undergo the IR procedure. Mice in the IR groups underwent 90 minutes of limb ischemia followed by a variable period of reperfusion. Ischemia was performed by applying a 4.5-oz orthodontic rubber band to the left thigh. Mice in one IR group were sacrificed immediately after reperfusion. The other 2 IR groups were injected once with either 0.75 g GLN/kg body weight (G group) or an equal volume of saline (S group) via tail vein before reperfusion. Mice in the S and G groups were subdivided and sacrificed at 4 or 24 hours after reperfusion. IR enhanced the inflammatory cytokine gene expressions in muscle. Also, plasma interleukin (IL)-6 levels, blood neutrophil percentage, and the adhesion molecule and chemokine receptors expressed by leukocytes were upregulated after reperfusion. The IR-induced muscle inflammatory mediator gene expressions, blood macrophage percentage, and plasma IL-6 concentration had declined at an early or a late phase of reperfusion when GLN was administered. Histologic findings also found that remote lung injury was attenuated during IR insult. A single dose of GLN administration immediately after sublethal lower limb ischemia reduces the inflammatory reaction locally and systemically; this may offer local and distant organ protection in hind limb IR injury.

APSC2015-1184 Vascular Complications After Detachment of Femoral Cannulation for Venoarterial Extracorporeal Membrane Oxygenation Support Caused by Limb Ischemia Reperfusion Injury

0 / 39 3/110 2/62 P O ST E R A B ST R A C T S Method: We identified 492 patients who had undergone PCI in a tertiary hospital in Singapore and randomised them into the intervention or control arms. Patients in the intervention arm were recruited into either the Post-Elective PCI or the Post-Acute Coronary Syndrome SCORE protocols. Patients were excluded if they had any of the following: planned for a staged PCI, left ventricular ejection fraction < 40%, atrial fibrillation, ventricular tachycardia, renal failure, anaemia or other co-morbidities that precluded discharge to primary care. The primary outcomes measured were discharge to primary care within 1 year, and achievement of low-density lipoprotein (LDL) level of < 2.6mmol/L within 1 year. Results: Among the intervention group, 215 out of 395 were discharged to primary care within 1 year, compared to 7 out of 99 in the control group (54.4% vs 7.1%, p<0.001). Furthermore, 328 out of 386 patients in the intervention group achieved the LDL target within 1 year, compared to 63 out of 89 in the control group (85.0% vs 70.8%, p1⁄40.002). After multivariable analysis, inclusion in the SCORE program was still independently associated with a higher chance of discharge to primary care and achieving the LDL target. Conclusion: SCORE improved the rate of discharge of post-PCI patients to primary care, and also improved the achievement of LDL targets. These findings support the implementation of a standardised follow-up protocol in patients who have undergone PCI. Disclosure of Interest: None Declared

Sheath-shunt technique for avoiding lower limb ischemia during complex endovascular aneurysm repair

Complex aortic aneurysms are now being repaired by endovascular techniques, albeit with a potentially increased risk of lower limb ischemia-reperfusion injury. We report a simple technique to maintain perfusion to the lower limb during endovascular repair, using one additional introducer sheath placed antegrade, distal to the stent graft introduction site, and connected to the side arm of the working sheath in the contralateral artery. This allows continuous perfusion of the limb distal to the main stent graft introduction site. In our initial experience with 12 cases, with confirmed occlusion of the native arterial system by the stent graft introducer sheath, arterial occlusion time was 165 ± 84 minutes. Use of the sheath-shunt technique resulted in pulsatile flow in all cases, with an average flow of 42.2 ± 13.2 mL/min, and actual ischemia time was reduced to 14 ± 11 minutes. There were no complications related to the use of this technique. Given the limited risk of this technique coupled with a potential benefit, we propose its consideration in patients undergoing complex endovascular repair.

Anti-oxidative stress effect of proanthocyanidin on intestinal mucosa of rats with limb ischemia-reperfusion injury

Anti-oxidative stress effect of proanthocyanidin on intestinal mucosa of rats with limb ischemia-reperfusion injury

Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression.

Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6), 12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

Effect of Mailuoning injection on 8-iso-prostaglandin F2 alpha and superoxide dismutase in rabbits with extremity ischemia–reperfusion injury

BackgroundTo date, there are no effective treatments for extremity ischemia–reperfusion (IR) injury. The objective of the present study was to explore the protective effect of Mailuoning on IR injury by investigating the plasma levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) and the activity of superoxide dismutase (SOD) in rabbits. Materials and methodsThe experimental models of posterior limb IR injury were established in thirty rabbits that were divided into three groups: the sham, IR, and IR + Mailuoning groups. At the end of ischemia, Mailuoning was injected intravenously into the rabbits in the IR + Mailuoning group, and normal saline solution was administered to the rabbits in the sham and IR groups. Venous blood samples were collected to measure the levels of 8-iso-PGF2α and the activity of SOD in the plasma at the following time points: at the onset of ischemia, the end of ischemia, and 2, 4, 8, 12, and 24 h after reperfusion. The skeletal muscles were harvested to examine the ultrastructure. ResultsThe levels of 8-iso-PGF2α increased significantly and SOD activity decreased in the IR group at every time point after reperfusion (P <0.01 or P <0.05). In contrast, the levels of 8-iso-PGF2α and SOD activity were not significantly different after reperfusion in the IR + Mailuoning group (P >0.05) but were significantly different compared with the IR group (P <0.01). Using electron microscopy, the skeletal muscle injury was shown to be milder in the IR+ Mailuoning group after reperfusion compared with the IR group. ConclusionsThe Mailuoning is capable of decreasing the excessive production of 8-iso-PGF2α and protecting SOD activity, thereby exhibiting a protective effect on extremity IR injury.