Tourniquet-induced Ischemia-reperfusion Research Articles

Comparison of the effects of axillary brachial plexus block, inhalation anesthesia, and total intravenous anesthesia on tourniquet-induced ischemia-reperfusion injury in upper extremity surgery.

Post-ischemia reperfusion can lead to oxidative stress and an increase in oxidative markers. Employing preventive strategies and antioxidant agents may help mitigate ischemia-reperfusion injury (IRI). The use of a tourniquet in extremity surgery has been associated with IRI. This study aims to investigate the impact of three different approaches- brachial plexus block, total intravenous anesthesia (TIVA), and inhalation anesthesia-on IRI during upper extremity surgery using a tourniquet. Patients aged 18 to 45 with American Society of Anesthesiologists (ASA) I-II scores were randomly assigned to one of three groups: Group A received an axillary block with bupivacaine; Group I underwent inhalation anesthesia with sevoflurane; and Group T received TIVA with propofol and remifentanil infusion. Blood samples were collected to measure glucose, lactate, total anti-oxidant status (TAS), total oxidant status (TOS), and ischemia-modified albumin (IMA) levels at various time points: before anesthesia (t1), 1 minute before tourniquet release (t2), 20 minutes after tourniquet release (t3), and 4 hours after tourniquet release (t4). In Group I, lactate levels at t3, and glucose levels at t2 and t3, were higher compared to the other groups. Group A exhibited lower IMA levels at t2, t3, and t4 than the other groups. Additionally, Group I had lower IMA levels at t2, t3, and t4 compared to Group T. TAS levels were higher in Group I at t2, t3, and t4 compared to the other groups. TOS levels at t2 and t3 were lower in Group A than in Group I. Axillary anesthesia results in a sympathetic block, promoting better perfusion of the upper extremity. This study demonstrated lower levels of oxidative stress markers with axillary plexus block. Therefore, these results suggest that the axillary block has the potential to mitigate IRI.

Inflammatory Responses of the Remote Organs After Tourniquet-Induced Ischemia-Reperfusion in Mouse Hindlimb

Tourniquet use is the most effective tool for controlling life-threatening extremity hemorrhage before other treatments and for creating bloodless operating fields in surgical procedures. However, tourniquet-induced ischemia-reperfusion (IR) also causes skeletal muscle injury and associated secondary end-organ damage. Our previous studies have demonstrated that there are involvements of inflammatory cytokines in tourniquet-induced skeletal muscle IR injuries. The objective of this study is to investigate the inflammatory responses of end-organs after tourniquet-induced mouse hindlimb IR. We hypothesized that tourniquet use would result in an inflammatory response in the remote organs. The unilateral hindlimbs of mice were subjected to 3 hours of tourniquet application by placing a rubber band at the hip joint. Then the rubber bands were released for reperfusion over different periods of time (1, 3, 7, and 14 days). The mRNA levels of IL-1β and TNFα (two inflammatory cytokines) in the lungs, liver, kidneys, and heart were measured using real-time RT-PCR analysis. In the lungs, the levels of IL-1β and TNFα mRNA were significantly elevated at day 1 after tourniquet-induced IR, then decreased at days 3 and 7, and returned to a high level at day 14. In the liver, the levels of IL-1β and TNFα mRNA were increased at day 1 and remained at a high level until day 14. However, tourniquet-induced hindlimb IR did not change the levels of IL-1β or TNFα mRNA in the kidneys or heart during the whole period of tourniquet-induced IR. In conclusion, these results suggest that the inflammatory response to tourniquet-induced hindlimb IR is different among distant organs, which will help to develop therapeutic strategies for different end-organs after tourniquet-induced hindlimb IR. NIH/NIGMS 1R01GM145736 to Y-LL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rapsyn overexpression improves recovery of the neuromuscular junction from tourniquet-induced ischemia-reperfusion injury in mouse hindlimb

The neuromuscular junction (NMJ) is an important factor to influence skeletal muscle contractile function. Tourniquet-induced ischemia-reperfusion (IR) results in the fragmentation of nicotinic acetylcholine receptors (nAChR) clusters in the NMJ and impairs neural controlled skeletal muscle contraction. Rapsyn, a cytoplasmic nAChR-associated protein concentrates and anchors nAChRs in the postsynaptic membrane and participates in the nAChR assembly at NMJ. Here, we observed the effect of overexpression of Rapsyn on morphological and functional recovery of the NMJ from tourniquet-induced IR injuries in mouse hindlimb. Unilateral hindlimb of C57/BL6 mice were subjected to 3 hours of ischemia by placing a rubber band and followed 6 weeks of reperfusion. Ad-m-RAPSN (5.2 x 1010 PFU/ml) was injected into gastrocnemius muscle (50 μl) by Hamilton microliter syringe after 2 weeks of tourniquet-induced IR. After 6 weeks of IR, the sciatic nerve-stimulated gastrocnemius muscle contraction and endplate potential (EPP) were recorded in in-situ muscle samples; the NMJs were labelled with alpha-bungarotoxin (BTX) and nerofilment-200 (NF-200) + synaptophysin (Syn) antibodies, and NMJ images were captured with Zeiss LSM 800. After 6 weeks of IR, NMJs in the gastrocnemius muscle showed significantly fragmented nAChR clusters (9.3 ± 0.7 vs. sham 1.7 ± 0.1 for numbers of fragments) with low rapsyn expression, and the EPP (15.29 ± 0.93 mV vs. sham 26.87 ± 0.89 mV) and nerve-stimulated muscle contraction (117.2 ± 8.5 g vs. sham 157.9 ± 4.9 g) were reduced. Ad-m-RAPSN injection increased rapsyn expression, mitigated fragmentation of nAChR clusters (3.2 ± 0.3), increased the EPP (20.35 ± 0.86) and nerve-stimulated muscle contraction (138.1 ± 3.5 g). The data suggest that tourniquet-related IR induces AChR cluster fragmentation and impairs NMJ function, and rapsyn overexpression improves the morphological and functional recovery of the NMJ from tourniquet-induced IR injuries.. This research is supported by the NIH/NIGMS 1R01GM145736 to Y-LL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effect of Infraclavicular Block on Tourniquet-Induced Ischaemia Reperfusion Injury: A Prospective Randomized Controlled Study

The Effect of Infraclavicular Block on Tourniquet-Induced Ischaemia Reperfusion Injury: A Prospective Randomized Controlled Study

Effect of Preoperative Administration of Oral Melatonin on Pneumatic Tourniquet-Induced Ischemia-Reperfusion Injury in Orthopedic Surgery of Lower Extremities: A Randomized Clinical Trial.

Background: Ischemic reperfusion injury (IRI) causes cellular damage and dysfunction. The present study aimed to evaluate the effect of melatonin on pneumatic tourniquet-induced IRI in orthopedic surgery of the lower extremities.Methods: A randomized clinical trial was conducted at Chamran Hospital, Shiraz University of Medical Sciences (Shiraz, Iran), from September to November 2019. The target population was patients scheduled for elective orthopedic surgery of the lower extremities. A total of 67 patients were randomly divided into two groups, placebo (n=34) and melatonin (n=33). The groups received 10 mg melatonin or placebo the night before surgery and two hours before surgery. Primary outcome variables were the serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Hemodynamic parameters, sedation score, and drug side effects were also evaluated. Data were analyzed using SPSS version 21.0 software. P<0.05 was considered statistically significant.Results: In the analysis phase, due to loss to follow-up (n=26), 41 patients divided into two groups of melatonin (n=20) and placebo (n=21) were evaluated. There was no significant difference in demographic data, duration of surgery (P=0.929), and tourniquet time (P=0.496) between the groups. The serum levels of SOD and MDA were not significantly different between the groups (P=0.866 and P=0.422, respectively), nor were the incidence of postoperative nausea (P=0.588) and patients’ satisfaction (P=0.088). However, the postoperative sedation score and vomiting between the groups were significantly different (P<0.001).Conclusion: Administration of 10 mg melatonin provided effective sedation, but had no significant effect on the serum levels of SOD and MDA, nor on pneumatic tourniquet-induced IRI in orthopedic surgery of the lower limbs.Trial registration number: IRCT20141009019470N87.

Effects of Dexmedetomidine and Oxycodone on Neurocognitive and Inflammatory Response After Tourniquet-Induced Ischemia-Reperfusion Injury.

To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia-reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n = 48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p<0.05), while Oxy had no significant effect on it. Compared with I/R group, Dex and Oxy treatment down-regulated the expression of NF-κB, TLR4, TNF-α and CD68 (all p<0.05), while no significantly different was found in CD206 and IL-10. In addition, Dex treatment down-regulated the expression of NR2B and reduced the frequency and amplitude of sEPSCs in I/R model mice (all p<0.05), while Oxy had no significant effect on them. Tourniquet-induced I/R could impair the neurocognitive function of mice. Dex treatment could alleviate I/R-induced neurocognitive disorder by inhibiting abnormal synaptic transmission in hippocampal neurons. Both Dex and Oxy could alleviate the inflammatory response likely by inhibiting the polarization of microglia toward M1 phenotype via TLR4/NF-κB pathway. Future studies are needed to further examine the effects of Dex on neurocognitive disorder after tourniquet-induced I/R injury and investigate the exact mechanism.

Association between Preoperative Long-Chain Polyunsaturated Fatty Acids and Oxidative Stress Immediately after Total Knee Arthroplasty: A Pilot Study.

Quadriceps muscle atrophy following total knee arthroplasty (TKA) can be caused by tourniquet-induced ischemia–reperfusion (IR) injury, which is often accompanied by oxidative stress and inflammatory responses. n-3 long-chain polyunsaturated fatty acids (LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antioxidant and anti-inflammatory effects against IR injury, whereas n-6 LCPUFAs, particularly arachidonic acid (AA), exhibit pro-inflammatory effects and promote IR injury. This study aimed to examine whether preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio are associated with oxidative stress immediately after TKA. Fourteen eligible patients with knee osteoarthritis scheduled for unilateral TKA participated in this study. The levels of serum EPA, DHA, and AA were measured immediately before surgery. Derivatives of reactive oxygen metabolites (d-ROMs) were used as biomarkers for oxidative stress. The preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio were found to be significantly negatively correlated with the serum d-ROM levels at 96 h after surgery, and the rate of increase in serum d-ROM levels between baseline and 96 h postoperatively. This study suggested the preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio can be negatively associated with oxidative stress immediately after TKA.

Does hyperbaric oxygen pretreatment with 100% oxygen attenuate tourniquet‐induced acute ischemia‐reperfusion injury in mouse hindlimb?

Tourniquet-induced ischemia-reperfusion (IR) leads to an increase in reactive oxygen species (ROS) production and tissue necrosis and apoptosis during reperfusion, which disrupts the recovery of skeletal muscle contraction. Hyperbaric oxygen (HBO) therapy exposes patients to high oxygen levels at an increased pressure, which increases the amount of ROS in tissues. Using HBO therapy as a pretreatment can promote ischemic tolerance by increasing antioxidant effects in these tissues before the IR injury. In this study, we observed the effects of HBO pretreatment with 100% oxygen at 2.5 ATA on tourniquet-induced IR injury in mice. C57/BL6 mice were treated with 100% oxygen for 60 minutes at 2.5 ATA in a HBO chamber. A rubber band was placed at the hip joint of the unilateral hindlimb of the mice to induce ischemia for 3 hours, which was followed by rubber band release and subsequent reperfusion for 48 hours. All staining and measurements were performed after the 48 hours of reperfusion. TTC staining of the gastrocnemius muscle showed no significant change in IR-induced infarct size after HBO pretreatment. ROS level was decreased in the gastrocnemius muscle of HBO-pretreated IR mice compared to non-HBO-pretreated IR mice. IR mice pretreated with HBO showed a decrease in ATP level in the gastrocnemius muscle compared to mice without HBO treatment. The data suggest that one hour HBO pretreatment with 100% oxygen at 2.5 ATA increases oxidative metabolism but does not decrease tissue necrosis in mice with tourniquet-induced IR injury.

Effects of preoperative low-intensity training with slow movement on early quadriceps weakness after total knee arthroplasty in patients with knee osteoarthritis: a retrospective propensity score-matched study

BackgroundSevere and early quadriceps weakness (QW) after total knee arthroplasty (TKA), which is caused by acute inflammation resulting from surgical trauma and tourniquet-induced ischemia-reperfusion (IR) injury, can be especially problematic. We focused on tourniquet-induced IR injury, because it has been shown to be preventable through ischemic and exercise preconditioning. Low-intensity resistance exercise with slow movement and tonic force generation (LST) share some similarities with ischemic and exercise preconditioning. The present study primarily aimed to clarify the efficacy of preoperative LST program as prehabilitation for early QW among patients with TKA using propensity score matching analysis.MethodsThis single-center retrospective observational study used data from patients with knee osteoarthritis (n = 277) who were scheduled to undergo unilateral TKA between August 2015 and January 2017. Those with missing outcome data due to their inability to perform tests were excluded. The LST group included participants who performed LST and aerobic exercise (LST session) more than seven times for three months prior to surgery. The control group included participants who performed less than eight LST sessions, a general and light exercise or had no exercise for three months prior to surgery. Knee circumference, thigh volume, knee pain during quadriceps strength test (QST) and timed up and go test (TUG), quadriceps strength, and TUG were measured before and 4 days after surgery. Knee swelling, thigh swelling, Δknee pain, QW, and ΔTUG were determined by comparing pre- and postoperative measurements.ResultsPropensity score matching generated 41 matched pairs who had nearly balanced characteristics. The LST group had a significantly lower knee and thigh swelling, QW, and ΔTUG compared to the control group (all, p < 0.05). No significant differences in Δknee pain during the QST and TUG were observed between both groups (both, p > 0.05).ConclusionsThe present study demonstrated the beneficial effects of preoperative LST program on knee swelling, thigh swelling, QW, and walking disability immediately after TKA.

Dexamethasone ameliorates recovery process of neuromuscular junctions after tourniquet-induced ischemia-reperfusion injuries in mouse hindlimb

As a primary tool in first-line treatment of severe extremity hemorrhage, tourniquet and subsequent reperfusion also induce ischemia-reperfusion (IR) injuries including severe dysfunction of the neuromuscular junction (NMJ). Here, we observed the effect of dexamethasone (Dex) on NMJs suffering from IR-cause damage in mouse hindlimb. Unilateral hindlimb of mice was subjected to 3 h of tourniquet application by placing a rubber band, and then releasing the rubber band for reperfusion during different periods of time (1, 2, 4, and 6 weeks). Dex treatment (1 mg/kg/day, i.p.) began on the day of tourniquet-IR induction and lasted for 7 days. During tourniquet-induced IR, NMJs in gastrocnemius muscles showed significant morphological and functional changes. These changes include that motor nerve terminals gradually regenerated, even reaching that seen in sham mice; nicotinic acetylcholine receptor (nAChR) clusters were gradually fragmented with prolongation of reperfusion; and the amplitude of endplate potentials (EPPs) gradually increased, but it did not restore to the sham level at 6 weeks of tourniquet-induced IR. IL-1β and TNFα were over-produced in gastrocnemius muscles at 1 week, gradually decreased to the sham level at 4 weeks, and returned back to a high level at 6 weeks of tourniquet-induced IR. Treatment with Dex mitigated fragmentation of nAChR clusters, increased the amplitude of EPPs, and decreased levels of TNFα and IL-1β during the first two weeks of tourniquet-induced IR. The present study suggests that anti-inflammation is a potentially important strategy for promoting the morphological and functional recovery processes of NMJs after tourniquet-induced IR injuries.

Effect of sevoflurane and propofol on tourniquet-induced endothelial damage: a pilot randomized controlled trial for knee-ligament surgery

BackgroundThe glycocalyx layer is a key structure in the endothelium. Tourniquet-induced ischemic periods are used during orthopedic surgery, and the reactive oxygen species generated after ischemia-reperfusion may mediate the shedding of the glycocalyx. Here, we describe the effects of tourniquet-induced ischemia-reperfusion and compare the effects of sevoflurane and propofol on the release of endothelial biomarkers after ischemia-reperfusion in knee-ligament surgery.MethodsThis pilot, single-center, blinded, randomized, controlled trial included 16 healthy patients. After spinal anesthesia, hypnosis was achieved with sevoflurane or propofol according to randomization. During the perioperative period, five venous blood samples were collected for quantification of syndecan-1, heparan sulfate, and thrombomodulin from blood serum by using ELISA assays kits. Sample size calculation was performed to detect a 25% change in the mean concentration of syndecan-1 with an alpha of 0.05 and power of 80%.ResultsFor our primary outcome, a two-way ANOVA with post-hoc Bonferroni correction analysis showed no differences in syndecan-1 concentrations between the sevoflurane and propofol groups at any time point. In the sevoflurane group, we noted an increase in syndecan-1 concentrations 90 min after tourniquet release in the sevoflurane group from 34.6 ± 24.4 ng/mL to 47.9 ± 29.8 ng/mL (Wilcoxon test, p < 0.01) that was not observed in patients randomized to the propofol group. The two-way ANOVA showed no intergroup differences in heparan sulfate and thrombomodulin levels.ConclusionsSuperficial endothelial damage without alterations in the cell layer integrity was observed after tourniquet knee-ligament surgery. There was no elevation in serum endothelial biomarkers in the propofol group patients. Sevoflurane did not show the protective effect observed in in vitro and in vivo studies.Trial registrationThe trial was registered in www.clinicaltrials.gov (ref: NCT03772054, Registered 11 December 2018).

Association between serum n-3 polyunsaturated fatty acids and quadriceps weakness immediately after total knee arthroplasty

ObjectivesQuadriceps weakness (QW) following total knee arthroplasty (TKA) can be elicited by tourniquet-induced ischaemia reperfusion (IR), which causes a vigorous acute inflammatory response. Dietary n-3 polyunsaturated fatty acids (PUFA) are important determinants of organ and tissue protection from IR. This study aimed to examine the association between serum n-3 PUFA levels and QW, knee pain, and knee swelling immediately after TKA.MethodsA total of 32 patients who underwent unilateral TKA participated in this prospective study. On Postoperative Day 1, serum n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) levels were measured. Preoperatively and on Postoperative Day 4, quadriceps strength, knee pain during quadriceps testing, and knee circumference were measured. QW, knee pain, and knee swelling were defined as changes in quadriceps strength, knee pain during quadriceps testing, and knee circumference, respectively, between the preoperative to the postoperative measurement.ResultsMean serum n-3 PUFA levels were 192 μg/mL (standard deviation, 58 μg/mL) on Postoperative Day 1. All measured variables changed significantly between the preoperative and the postoperative measurement time-points (P <0.01). Quadriceps strength decreased from 1.2 to 0.4 Nm/kg (QW = −65%). Knee pain during quadriceps testing increased from 1.1 to 6.0 (knee pain = 4.0). Knee circumference increased from 40 to 44 cm (knee swelling = 10%). Multivariate analysis showed that lower serum n-3 PUFA levels were independently associated with an increased QW after adjusting for the Kellgren-Lawrence grade and the tourniquet time (P = 0.04). No significant relationship was observed between serum n-3 PUFA levels and knee pain or knee swelling.ConclusionHigher serum n-3 PUFA are independently associated with a lower increase in the QW immediately after TKA.

Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus.

The effect of pregabalin on tourniquet-induced ischemia-reperfusion injury: a prospective randomized study

Background/aim The aim of this study was to investigate the efficacy of pregabalin on ischemia-reperfusion injuries.Materials and methods Fifty-four patients were randomly assigned into 2 groups. A 150-mg tablet of pregabalin was given the night before and then 1 h before the operation for patients in Group P (pregabalin group, n = 27). A placebo was given to patients in Group C (control group, n = 27) at the same times. After combined spinal-epidural anesthesia was performed, venous blood samples were taken before tourniquet inflation (t1), just before tourniquet deflation (t2), and 20 min after tourniquet deflation (t3) for the analysis of total antioxidant status (TAS), total oxidant status (TOS), catalase (CAT), and ischemia-modified albumin (IMA).Results There was no significant difference in TAS levels between the groups for the t3 period. However, the TAS in Group P was significantly higher in the t3 period than the t2 period (mean ± SD, 0.46 ± 0.1 vs. 0.38 ± 0.2 mmol of Trolox equivalent/L, respectively; P < 0.05). The CAT level in the t3 period was significantly higher in Group P than Group C (mean ± SD, 53.04 ± 32.1 vs. 35.46 ± 17.2 µmol/formaldehyde, respectively; P < 0.05). In the t3 period, the TOS was significantly lower in Group P than Group C (mean ± SD, 11.97 ± 5 vs. 18.29 ± 9.9 pg/mL, respectively; P < 0.05). The TOS in Group P was significantly lower in the t3 period than the t2 period (mean ± SD, 11.97 ± 5 vs. 18.98 ± 10.7 pg/mL, respectively; P < 0.0001).Conclusion Pregabalin has no marked antioxidant activity, but it contributes to the antioxidant defense system of an organism.

The Possible Pathophysiological Outcomes and Mechanisms of Tourniquet-Induced Ischemia-Reperfusion Injury during Total Knee Arthroplasty.

Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords “ischemia reperfusion injury,” “oxidative stress,” “tourniquet,” and “knee arthroplasty.” The search was limited to research articles published in the English language. Twenty-eight clinical studies were included in this qualitative review. Skeletal muscle I/R reduces protein synthesis, increases protein degradation, and upregulates genes in cell stress pathways. The I/R of the lower extremity elevates local and systemic oxidative stress as well as inflammatory reactions and impairs renal function. Propofol reduces oxidative injury in this I/R model. Ischemic preconditioning (IPC) and vitamin C may prevent oxygen free radical production. However, a high dose of N-acetylcysteine possibly induces kidney injury. In summary, TQ-related I/R during TKA leads to muscle protein metabolism alteration, endothelial dysfunction, oxidative stress, inflammatory response, and renal function disturbance. Propofol, IPC, and vitamin C show protective effects on oxidative and inflammatory markers. However, a relationship between biochemical parameters and postoperative clinical outcomes has not been validated.

Effects of dexmedetomidine on inflammatory mediators after tourniquet-induced ischemia-reperfusion injury: a randomized, double-blinded, controlled study.

Tourniquet use during total knee arthroplasty (TKA) produces ischemia-reperfusion injury (IRI), with systemic release of inflammatory cytokines and reactive oxygen species upon tourniquet release. We conducted a randomized, placebo-controlled, double-blind trial to examine whether dexmedetomidine (DEX) as an adjunct during general anesthesia in patients undergoing unilateral TKA could attenuate the rise in inflammatory cytokines and oxidative stress. Sixty-eight patients were randomized to either the control or DEX group. DEX was administered at a loading dose of 0.5 μg/kg, followed by an infusion of 0.4 μg/kg/h. We measured serum levels of malondialdehyde (biomarker of oxidative stress) and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) preinduction (baseline), 60 and 90 min post-tourniquet release. We also assessed hemodynamics, intraoperative remifentanil consumption, and postoperative pain scores and analgesic consumption. Malondialdehyde was higher than baseline after tourniquet release in both groups (P≤0.001), but the levels were similar between groups at all times. TNF-α was significantly higher than baseline at 60 min post-tourniquet release only in the control group (P=0.009). Serum IL-6 increased significantly above baseline at 60 and 90 min post-tourniquet release in both groups (P<0.001). At 90 min, IL-6 was significantly lower in the dexmedetomidine group than in the control group (P=0.049). Remifentanil consumption, heart rate, and pain scores were significantly lower in the dexmedetomidine group. Our results suggest that dexmedetomidine as an adjunct to general anesthesia attenuated the rise in proinflammatory cytokines, providing protective effects in tourniquet-induced IRI.

Tourniquet-Induced Ischemia-Reperfusion Injury during Total Knee Arthroplasty

Tourniquet-Induced Ischemia-Reperfusion Injury during Total Knee Arthroplasty

The effects of ketamine and lidocaine on free radical production after tourniquet-induced ischemia-reperfusion injury in adults.

The primary aim of this study was to compare the effects of a small-dose infusion of 2 antioxidant agents, ketamine and lidocaine, on ischemia-reperfusion injury (IRI) in patients undergoing elective lower limb surgery. Ischemia-modified albumin (IMA), lactate, and blood gas levels were all measured and assessed. A total of 100 patients who underwent lower extremity surgery were randomized into 3 groups. After spinal anesthesia, the ketamine group (Group K, n=33) was given a ketamine infusion, a lidocaine infusion was administered to the lidocaine group (Group L, n=33), and in the control group (Group C), 0.9% a sodium chloride infusion was performed. Blood samples were obtained for IMA analysis before anesthetic administration (baseline), at 30 minutes of tourniquet inflation (ischemia), and 15 minutes after tourniquet deflation (reperfusion). Arterial blood gas measurements were determined before anesthetic administration and 15 minutes after tourniquet deflation. The lactate and IMA levels at reperfusion were significantly lower in both the ketamine group and the lidocaine group when compared with the control group. The administration of both ketamine and lidocaine infusions significantly decreased skeletal muscle IRI-related high lactate and IMA levels. These results suggest the possibility of the clinical application of ketamine or lidocaine infusions in cases of skeletal muscle-related IRI.

A study of the relationships of changes in pain and gait after tourniquet-induced ischemia-reperfusion in rats.

[Purpose] The purpose of this study was to determine the relationships of changes in pain and gait after ischemia reperfusion was induced by tourniquet in rats. [Subjects and Methods] The subjects were six ten-week-old male Wistar rats. Ischemia was induced in the left lower limbs of the experimental rats at a pressure of 300 mmHg for 90 minutes. Pain behavior evaluations were measured using the von Frey test in all the rats’ hind limbs. A consistently increasing plantar stimulus was applied until the rats exhibited an escape behavior. For the evaluation of gait, a two-dimensional motion analysis system was used to measure the distance from the calcaneus to the floor (DCF) and toe extension angle (TEA) during gait. The evaluations were performed in the normal state, 3 hours after ischemia-reperfusion, and daily until 7 days after ischemia-reperfusion. [Results] Compared with the normal state, the means of the pain threshold showed a significant decrease until 4 days after ischemia. In addition, both TEA and DCF continued to show a significant decrease at 7 days after ischemia as compared with the normal state. [Conclusion] This study revealed that hyperalgesia occurs after ischemia-reperfusion, and recovery of hyperalgesia occurred earlier than gait dysfunction recovery.

Dexamethasone promotes long-term functional recovery of neuromuscular junction in a murine model of tourniquet-induced ischaemia-reperfusion.

Tourniquet-induced ischaemia and subsequent reperfusion cause serious ischaemia-reperfusion (IR) injury in the neuromuscular junction (NMJ) and skeletal muscle. Here, we investigated whether dexamethasone (Dex) promotes long-term functional recovery of the NMJ and skeletal muscle in tourniquet-induced hindlimb IR. Unilateral hindlimb of C57/BL6 mice was subjected to 3h of ischaemia following 6weeks of reperfusion (6-wk IR). Dex treatment began on the day of IR induction and lasted for different periods. Sciatic nerve-stimulated gastrocnemius muscle contraction was detected insitu. Function of the NMJ was measured insitu using electrophysiological recording of the miniature endplate potential (mEPP) and endplate potential (EPP). Western blot was used to detect protein expression of nicotinic acetylcholine receptors (nAChRs) in gastrocnemius muscles. Gastrocnemius muscle contraction in mice with 6-wk IR was about 60% of normal skeletal muscle contraction recorded in age-matched sham mice. The amplitude of the mEPP and EPP was lower in mice with 6-wk IR, compared to sham mice. Dex treatment for 1 or 3days did not restore the function of the NMJ and improve gastrocnemius muscle contraction in mice with 6-wk IR. Dex treatment for 1week exerted a maximum effect on improving the function of the NMJ and skeletal muscle, with the effect of Dex gradually lessening with prolonged Dex treatment. There are no significant differences in protein expression of nAChR-α1 and nAChR-β1 subunits in the gastrocnemius muscle among all groups. Dex promotes repair of the NMJ and subsequently restores skeletal muscle contractile function in tourniquet-induced 6-wk IR.