Search Results (18)

Introduction: Many orthopedic surgeons recommend ischemic tourniquets during arthroscopic anterior cruciate ligament (ACL) repair to reduce blood loss and improve visibility. However, their use remains controversial due to potential complications. Similarly, the practice of postoperative drainage is debated. While its proponents argue it reduces limb swelling, DVT, adhesions, and stiffness, others contend that it may increase infection risk or harm the ACL graft and joint surfaces. Materials and Methods: A total of 456 patients underwent anterior cruciate ligament reconstruction between September 2015 and December 2024, without the use of a tourniquet or drainage. The patients were 334 men with a mean age of 34.7 years and 122 women with a mean age of 32.3 years. In 389 cases the graft type was a hamstring autograft, in 55 cases a patellar tendon autograft (BPTB) was used, and in 12 cases a quadriceps tendon autograft was used. Results: The mean operative time was 61 min (range 52–79). No cases experienced visual impairment or required ischemia to enhance visibility. Bleeding sites were successfully cauterized during arthroscopy. Postoperative complications included knee hematoma in three patients (0.7%), resolved after drainage on day one, and two infections (0.4%), treated successfully with arthroscopic drainage and implant removal. No further complications were reported. Conclusion: Although many orthopedic surgeons prefer arthroscopic ACL repair with a tourniquet for better visibility and reduced intraoperative blood loss, this approach carries risks such as nerve palsy, joint swelling, stiffness, muscle weakness, and vascular changes. Not using a tourniquet can help to identify bleeding sites and allows for a more thorough procedure. The literature suggests that avoiding a tourniquet also reduces postoperative pain and accelerates recovery. The mean operative time for ACL reconstruction was consistent with the literature, indicating that avoiding a tourniquet did not cause delays. Additionally, the absence of postoperative drainage did not lead to complications, with most patients showing no issues like bleeding, hematoma, ischemia, or poor wound healing. Full article

Brain-derived neurotropic factor (BDNF) is expressed by skeletal muscle as a myokine. Our previous work showed that the active precursor, proBDNF, is the predominant form of BDNF expressed in skeletal muscle, and that following skeletal muscle injury, proBDNF levels are significantly increased. However, the function of the muscle-derived proBDNF in injury-induced inflammation has yet to be fully understood. Using a model of tourniquet-induced ischemia–reperfusion (IR) injury of the hindlimb, this study presents, for the first time, strong and novel evidence that following IR injury, proBDNF is released from skeletal muscle into circulation as an endocrine signaling molecule. Further, this study shows that 1 day post-IR injury, the proBDNF receptor, p75^NTR, is upregulated 12-fold in splenic monocytes, which are known to be quickly mobilized to the injury site. We demonstrate that p75^NTR plays a role in the activation of splenic monocytes, and that treatment with a p75^NTR small-molecule modulator, LM11A-31, significantly reduced monocyte inflammatory responses upon lipopolysaccharide stimulation. Overall, the present study establishes proBDNF as a myokine that plays a significant role in skeletal muscle injury-induced inflammation through its receptor, p75^NTR, which may be modulated using LM11A-31 as potential translational therapeutic against injury and inflammation. Full article

Introduction: The Wide Awake Local Anesthesia No Tourniquet (WALANT) technique has revolutionized outpatient hand surgery, enabling procedures such as carpal tunnel release and trigger finger release without a tourniquet. Its benefits include patient cooperation during surgery, especially for tendon repairs. However, WALANT has limitations, including a steep learning curve, longer operative preparation time, and risks such as digital ischemia and adrenaline-induced cardiac ischemia. This study evaluates the safety and effectiveness of local anesthesia with a tourniquet for short-duration outpatient hand surgeries. Materials and Methods: This case series included 300 patients undergoing carpal tunnel or trigger finger release between February 2023 and March 2024. Local anesthesia with lidocaine was administered, and a tourniquet was applied to the proximal arm. Demographic data, operative time, and pain levels during tourniquet use (measured by VAS) were recorded. Results: The average surgical time was 12 min. Most procedures involved carpal tunnel release. The average VAS pain score was 3.73, with older patients and longer surgeries reporting higher discomfort. Tourniquet release was required in only 1% of cases due to discomfort. Conclusions: For short outpatient hand surgeries, local anesthesia with a tourniquet is a safe, effective alternative to WALANT, challenging its routine use and highlighting the need for tailored anesthetic approaches. Full article

Extremity trauma, including ischemia (e.g., prolonged tourniquet application or crush), is common among battlefield injuries. Injured muscle releases toxins leading to rhabdomyolysis and, potentially, acute kidney injury (AKI). The goal of this study was to characterize sequelae of ischemic extremity injury over 72 h, focusing on time courses of rhabdomyolysis and AKI. Male Sprague Dawley rats were placed into two groups. Ischemic injury was produced in anesthetized rats using bilateral tourniquets (TK; n = 10) for 5 h; control (CON; n = 9) rats were treated identically without TK application. Indicators of rhabdomyolysis and renal function were measured in conscious rats 1 day preinjury (baseline, BL) and then at 1.5, 24, 48, and 72 h post-TK release. Prolonged TK application produced necrosis in both muscle and bone marrow but not in kidney. The wet/dry weights indicated edema in injured limbs at 72 h (4.1 (0.5) (TK) vs. 2.9 (0.1) (CON); p < 0.001). TK rats exhibited a 100-fold increase in creatine kinase activity compared to CON at 1.5 h (20,040 (7265) U/L vs. 195 (86) U/L (mean (SD); p < 0.0001). TK decreased the mean glomerular filtration rate (GFR; p < 0.001) at 1.5 h, but these values recovered by 24 h in concert with elevated urinary flow and alkalinization. Prolonged ischemic extremity injury therefore produced severe rhabdomyolysis without irreversible renal damage. Full article

Acute limb ischemia (ALI) is a sudden lack of blood flow to a limb, primarily caused by arterial embolism and thrombosis. Various experimental animal models, including non-invasive and invasive methods, have been developed and successfully used to induce limb ischemia-reperfusion injuries (L-IRI). However, there is no consensus on the methodologies used in animal models for L-IRI, particularly regarding the assessment of functional recovery. The present study aims to compare different approaches that induce L-IRI and determine the optimal animal model to study functional limb recovery. In this study, we applied a pneumatic cuff as a non-invasive method and ligated the aorta, iliac, or femoral artery as invasive methods to induce L-IRI. We have measured grip strength, motor function, creatine kinase level, inflammatory markers such as nuclear factor NF-κB, interleukin-6 (IL-6), hypoxia markers such as hypoxia-induced factor-1$\mathsf{\alpha }$ (HIF-1$\mathsf{\alpha }$), and evaluated the muscle injury with hematoxylin and eosin (H&E) staining in Sprague Dawley rats after inducing L-IRI. The pneumatic pressure cuff method significantly decreased the muscle strength of the rats, causing the loss of ability to hold the grid and inducing significant limb function impairment, while artery ligations did not. We conclude from this study that the tourniquet cuff method could be ideal for studying functional recovery after L-IRI in the rat model. Full article

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, in temporary clamping of the aorta in aortic surgery, or following acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress such as DM. Cerium oxide (CeO₂) nanoparticles mimic antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO₂ has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n = 6), diabetes group (group D, n = 8), diabetes–CeO₂ (group DCO, n = 8), diabetes–ischemia/reperfusion (group DIR, n = 8), and diabetes–ischemia/reperfusion–CeO₂ (group DIRCO, n = 8). The DCO and DIRCO groups were given doses of CeO₂ of 0.5 mg/kg intraperitoneally 30 min before the IR procedure. A 120 min ischemia–120 min reperfusion period with 100% O₂ was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p = 0.047 and p = 0.022, respectively). In group DIRCO, total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p < 0.001). The oxidative stress index (OSI) was found to be significantly lower in group DIR compared with group DCO (p < 0.001). Paraoxanase (PON) enzyme activity was found to be significantly increased in group DIR compared with group DCO (p < 0.001). The disorganization and degeneration score for muscle cells, inflammatory cell infiltration score, and total injury score in group DIRCO were found to be significantly lower than in group DIR (p = 0.002, p = 0.034, and p = 0.001, respectively). Conclusions: Our results confirm that CeO₂, with its antioxidative properties, reduces skeletal muscle damage in lower extremity IRI in diabetic mice. Full article

Brain-derived neurotropic factor (BDNF) has been shown to be expressed in many nonneuronal tissues including skeletal muscle. Skeletal muscle BDNF has been studied regarding its function in metabolism and exercise; however, less is known about its role in skeletal muscle injury. The precursor to BDNF, proBDNF, has an unknown role in skeletal muscle. The levels of proBDNF, mature BDNF, and their receptors were compared in the skeletal muscle and brain tissues of C57BL/6J mice. Tourniquet-induced hind limb ischemia-reperfusion injury was used to assess the function of skeletal muscle-derived proBDNF in skeletal muscle injury. Skeletal muscle-specific knockout of BDNF and pharmacological inhibition of p75NTR, the proBDNF receptor, were used to determine the role of proBDNF–p75NTR signaling. We show for the first time that proBDNF is the predominantly expressed form of BDNF in skeletal muscle and that proBDNF is significantly upregulated in skeletal muscle following hind limb ischemia-reperfusion injury. Skeletal muscle-specific knockout of BDNF blunted the inflammatory response in the injured tissue and appears to be mediated by the proBDNF–p75NTR pathway, as shown by the pharmacological inhibition of p75NTR. These findings suggest that skeletal muscle proBDNF plays a critical role in driving the inflammatory response following skeletal muscle injury. Full article

Blood removal with air tourniquets for a long time induces muscle damage after reperfusion. Ischemic preconditioning (IPC) has a protective effect against ischemia-reperfusion injury in striated muscle and myocardium. However, the mechanism of action of IPC on skeletal muscle injury is unclear. Thus, this study aimed to investigate the effect of IPC in reducing skeletal muscle damage caused by ischemia-reperfusion injury. The hindlimbs of 6-month-old rats were wounded with air tourniquets at a carminative blood pressure of 300 mmHg on the thighs. Rats were divided into the IPC (−) group and the IPC (+) group. The vascular endothelial growth factor (VEGF), 8-hydroxyguanosine (8-OHdG), and cyclooxygenase 2 (COX-2) were investigated by protein levels. Quantitative analysis of apoptosis was performed using the TUNEL method. Compared with the IPC (−) group, the IPC (+) group retained the VEGF expression, and the COX-2 and 8-OHdG expressions were suppressed. The proportion of apoptosis cells decreased in the IPC (+) group compared with the IPC (−) group. IPC in skeletal muscles proliferated VEGF and suppressed inflammatory response and oxidative DNA damage. IPC has the potential to reduce muscle damage after ischemia-reperfusion. Full article

Ischemia-reperfusion (I/R) injury is a complication impacting multiple organs and tissues in clinical conditions ranging from peripheral arterial disease to musculoskeletal trauma and myocardial infarction. Stem cell-derived extracellular vesicles (EVs) may represent one therapeutic resource for preventing the tissue damage associated with I/R injury. Here we tested the hypothesis that lyophilized extracellular vesicles derived from adipose stem cells could serve as an “off-the-shelf” treatment modality for I/R injury in a mouse hindlimb ischemia model. Ischemia was induced for 90 min using a rubber band tourniquet and extracellular vesicles (0, 50, or 100 µg) administered via tail vein injection immediately prior to reperfusion. Perfusion was measured prior to, during, and after ischemia using laser Doppler imaging. Serum and tissue were collected 24 h after reperfusion. Mass spectrometry (MS)-based proteomics was used to characterize the EV cargo and proteins from the ischemic and non-ischemic hindlimb. Inflammatory cytokines were measured in muscle and serum using a multiplex array. Results indicate that EVs significantly increase reperfusion and significantly increase expression of the anti-inflammatory factor annexin a1 in skeletal muscle; however, the increased reperfusion was also associated with a marked decrease in muscle structural proteins such as dystrophin, plectin, and obscurin. Circulating inflammatory cytokines TNF-alpha and IL-6 were increased with EV treatment, and serum TNF-alpha showed a significant, positive correlation with reperfusion level. These findings suggest that, while EVs may enhance reperfusion, the increased reperfusion can negatively impact muscle tissue and possibly remote organs. Alternative approaches, such as targeting mitochondrial permeability, may be more effective at mitigating I/R injury. Full article

Among the main preventable causes of death in the area of operations is external exsanguinating hemorrhage in the extremities, hence the importance of the tourniquet as a therapeutic tool in this type of injury and, therefore, of the training of personnel participating in international missions. The main objective of this study is to determine the impact of training in the application of this device. This is a quasi-experimental, prospective, cross-sectional study, carried out with 97 healthy volunteers, military personnel who perform their work in the Royal Guard barracks of El Pardo. The study was conducted between June 2019 and July 2021. The correct determination of the device placement site and the times of correct device placement were evaluated by determining whether there was blood flow using Doppler ultrasound measurements. Statistically significant results were obtained for application time (76.68 s to 58.06 s; p < 0.001), correct device placement (p < 0.001), and achievement of complete ischemia in the upper extremity (23.7% pretest vs. 24.7% post-test; p < 0.001). In the lower extremity, after training, longer application duration (43.33 s to 47.30 s) and lower ischemia achievement (59.8% pretest vs. 37.8% post-test) were obtained. Standardized and regulated training improves device application. More intensive training is necessary to obtain better results. Full article

Background: Lower limb ischemia-reperfusion injury (IRI-LL) is a common major complication of orthopedic surgery, especially in elderly patients. It has previously been demonstrated that folinic acid (FA) reduced IRI-LL damage in 3–4-month-old rats. This current work analyses the effect of FA in the prevention of IRI-LL in elderly animals. Methods: Forty-two 18-month-old male WAG/RijHsd rats were subjected to 3 h of ischemia. Eighteen animals received FA (2.5 mg/kg, ip) 20 min before the end of the ischemia period, while the other half received the same volume of saline solution. The animals were sacrificed after 3 h, 24 h, and 14 days of reperfusion for biochemical (tissue damage markers and electrolytes), histopathological studies of the gastrocnemius muscle and the daily assessment of the limb function by the Rota Rod test, respectively. Results: The administration of FA prior to the end of the ischemia period reduced the increase in LDH and CK observed in non-treated animals by 30–40% (p < 0.0001). When the histological sections were analyzed, FA was found to have reduced the number of damaged muscle fibers per field by 20% (60 ± 17.1 vs. 80.7 ± 16.4, p < 0.0001). The functional test revealed that FA also led to an improvement in the muscle function, assessed by the length of time that the animals kept running on the rod, compared to untreated animals. Conclusions: The administration of FA, prior to the end of the ischemic period, decreases the damage induced by IRI-LL, also achieving a faster recovery of mobility. Full article

Background: The exact influence of tourniquet ischemia on a treated extremity remains unclear. Methods: Twenty patients received an operation on one hand under tourniquet ischemia. Twenty healthy volunteers received 10 min of tourniquet ischemia on one of their arms. Measurements of tissue oxygen saturation using near-infrared reflectance-based imaging and skin temperature of the dorsum of the hand were performed at five different timepoints (t0 was performed just before the application of the tourniquet ischemia, t1 directly after the application of the tourniquet ischemia, t2 before the release of the ischemia, t3 directly after the release of the ischemia, and t4 on the following day). Results: In both groups, tissue oxygen saturation dropped after the application of the tourniquet ischemia compared to t0 and increased after the release of the tourniquet ischemia. In the patient group, tissue oxygen saturation at t4 was higher compared to t0; in contrast, the level of tissue oxygen saturation in the participant group dropped slightly at t4 compared to t0. The measured skin temperature in the patient group showed an increase during the observation period, while it continuously decreased in the group of healthy participants. Conclusions: Short-term ischemia did not appear to permanently restrict perfusion in this study design. The non-invasive imaging modalities used were easy to handle and allowed repetitive measurement. Full article

Tourniquet (TQ) use during total knee arthroplasty (TKA) induces ischemia/reperfusion (I/R) injury, resulting in mitochondrial dysfunction. This study aims to determine the effects of coenzyme Q10 (CoQ10) and ischemic preconditioning (IPC), either alone or in combination, on I/R-induced mitochondrial respiration alteration in peripheral blood mononuclear cells (PBMCs) and pain following TKA. Forty-four patients were allocated into four groups: control, CoQ10, IPC, and CoQ10 + IPC. CoQ10 dose was 300 mg/day for 28 days. IPC protocol was three cycles of 5/5-min I/R time. Mitochondrial oxygen consumption rates (OCRs) of PBMCs were measured seven times, at baseline and during ischemic/reperfusion phases, with XFe 96 extracellular flux analyzer. Postoperative pain was assessed for 48 h. CoQ10 improved baseline mitochondrial uncoupling state; however, changes in OCRs during the early phase of I/R were not significantly different from the placebo. Compared to ischemic data, IPC transiently increased basal OCR and ATP production at 2 h after reperfusion. Clinically, CoQ10 significantly decreased pain scores and morphine requirements at 24 h. CoQ10 + IPC abolished analgesic effect of CoQ10 and mitochondrial protection of IPC. In TKA with TQ, IPC enhanced mitochondrial function by a transient increase in basal and ATP-linked respiration, and CoQ10 provides postoperative analgesic effect. Surprisingly, CoQ10 + IPC interferes with beneficial effects of each intervention. Full article

Surgery under ischemic conditions, lasting up to 3 h, is routinely performed in orthopedic surgery, causing undesirable injury due to ischemia-reperfusion syndrome, with short and medium-term functional repercussions. To date, there is no established prophylactic treatment. In this work we evaluated folinic acid (FA) in a rodent model of lower limb ischemia-reperfusion (IRI-LL). 36 male WAG rats underwent 3 h of lower limb ischemia. In the saline group, rats received intraperitoneal administration of saline (used as vehicle for treatment). In the experimental group, rats were pretreated with FA (2.5 mg/kg) before the end of ischemia. After ischemia, animals were sacrificed at 3 h, 24 h or 14 days (for biochemical determination (Na+, K+, Cl-, urea, creatinine, CK, LDH, ALP, ALT, and AST), pathological assessment, or functional study using the rotarod test; respectively). Another six animals were used to establish the reference values. The prophylactic administration of FA significantly reduced the elevation of biochemical markers, especially those that most directly indicate muscle damage (CK and LDH). In addition, it also improved direct tissue damage, both in terms of edema, weight, PMN infiltrate and percentage of damaged fibers. Finally, the administration of FA allowed the animals to equal baseline values in the rotarod test; what did not occur in the saline group, where pre-ischemia levels were not recovered. Following 3 h of lower limb ischemia, FA minimizes the increase of CK and LDH, as well as local edema and leukocyte infiltration, allowing a faster recovery of limb functionality. Therefore, it could be considered as a prophylactic treatment when tourniquet is used in clinics. Full article

In trauma and orthopedic surgery, limb ischemia-reperfusion (I/R) remains a great challenge. The effect of preventive protocols, including surgical conditioning approaches, is still controversial. We aimed to examine the effects of local ischemic pre-conditioning (PreC) and post-conditioning (PostC) on limb I/R. Anesthetized rats were randomized into sham-operated (control), I/R (120-min limb ischemia with tourniquet), PreC, or PostC groups (3 × 10-min tourniquet ischemia, 10-min reperfusion intervals). Blood samples were taken before and just after the ischemia, and on the first postoperative week for testing hematological, micro-rheological (erythrocyte deformability and aggregation), and metabolic parameters. Histological samples were also taken. Erythrocyte count, hemoglobin, and hematocrit values decreased, while after a temporary decrease, platelet count increased in I/R groups. Erythrocyte deformability impairment and aggregation enhancement were seen after ischemia, more obviously in the PreC group, and less in PostC. Blood pH decreased in all I/R groups. The elevation of creatinine and lactate concentration was the largest in PostC group. Histology did not reveal important differences. In conclusion, limb I/R caused micro-rheological impairment with hematological and metabolic changes. Ischemic pre- and post-conditioning had additive changes in various manners. Post-conditioning showed better micro-rheological effects. However, by these parameters it cannot be decided which protocol is better. Full article