Aims. Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy. Methods. For patients undergoing short knee arthroscopic procedures, a sterile calibrated pH probe was inserted into the anterior fascial compartment of the leg after skin preparation, but before tourniquet inflation. The limb was elevated for three minutes prior to tourniquet inflation to 250 mmHg or 300 mmHg. Intramuscular pH was recorded at one-second intervals throughout the procedure and for 20 minutes following tourniquet deflation. Probe-related adverse events were recorded. Results. A total of 27 patients were recruited to the study. Mean tourniquet time was 21 minutes (10 to 56). Tourniquet pressure was 300 mmHg for 21 patients and 250 mmHg for six patients. Mean muscle pH prior to tourniquet inflation was 6.80. Muscle pH decreased upon tourniquet inflation, with a steeper fall in the first ten minutes than for the rest of the procedure. Change in muscle pH was significant after five minutes of tourniquet ischaemia (p < 0.001). Mean muscle pH prior to tourniquet release was 6.58 and recovered to 6.75 within 20 minutes following release. No probe related adverse events were recorded. Conclusion. It is possible to directly measure skeletal muscle pH in human subjects over time. Tourniquet ischaemia results in a decrease in human skeletal muscle pH over time during short procedures. Cite this article: Bone Joint Res 2021;10(6):363–369

1. The types of ischaemia that accompany injuries to a limb are described. 2. The ischaemia may be total or local. 3. Thirty-seven cases of total or local ischaemia of a limb are analysed and conclusions are drawn therefrom

Aims. Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. Methods. A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia. Results. GIK treatment resulted in a significant protection of skeletal muscle with increased viability (GIK 22.07% (SD 15.48%)) compared to saline control (control 3.14% (SD 3.29%)) (p = 0.005). Additionally, GIK led to a statistically significant reduction in gene expression markers of cell death (CASP3, p < 0.001) and inflammation (NOS2, p < 0.001; IGF1, p = 0.007; IL-1β, p = 0.002; TNFα, p = 0.012), and a significant reduction in serum creatine kinase (p = 0.004) and creatinine (p < 0.001). GIK led to a significant reduction in IR-related pain (p = 0.030). Conclusion. Systemic GIK infusion during and after limb ischaemia protects murine skeletal muscle from cell death, kidneys from reperfusion metabolites, and reduces pain by reducing post-ischaemic inflammation. Cite this article: Bone Joint Res 2023;12(3):212–218

Ischaemia kills osteocytes, but opinions differ as to how long they can survive. These differences are due to the varying methods of inducing ischaemia, and to the different criteria for diagnosing cell death. Using rabbit bone and a technique of in vitro ischaemia at 37 degrees C, we have shown by electron microscopy that, after up to two hours, the changes which occur are probably reversible; after four hours, the cells were irreversibly damaged. This difference could not be detected by light microscopy. After 24 hours of ischaemia, most lacunae were empty or contained only osteocyte debris. We conclude that osteocytes suffer irreversible damage after in vitro ischaemia of about two hours, which is much the same response as that of most other mammalian cells

1. A patient with complete ischaemia of the muscles of the calf and anterior compartment of the leg is described. 2. In diagnosis, tenseness of the calf, equinus and pain on attempted dorsiflexion of the ankle are most important. 3. Peripheral pulses may be present and do not contra-indicate decompression by operation to prevent ischaemia

Aims: The pathomechanism of avascular necrosis of the femoral head (AVN) is still debated. Hip joint synovitis and effusion may impair blood ßow to the femoral head. The critical ischemia time is around 6 hours, but repeated ischemic episodes may impair reperfusion and elicit AVN. The aims of this study were to investigate the value of dynamic MRI in femoral head after ischemia and during reperfusion. Methods: In 15 domestic pigs, 3–4 months old, femoral head ischemia was achieved by raising the joint pressure to 250 mmHg by dextran infusion through a hole in the acetabular wall. MRI was performed (Philips gyroscan S15, 1.5 T, Gd-DTPA enhancement, dynamic imaging interval 39 sec.) before ischemia, after 6 hours of ischemia, and again after 4 hours of reperfusion. Results: Signal intensity versus time (SI/t) plots were constructed from 347 MR studies. By regression analysis of SI/t curves an index (enhancement/decrease) was developed as criterion for arterial or venous circulatory disturbance. Index values < 1.1 signiþed arterial impairment, > 100 venous disturbance. Values between 1.1 and 100 were considered normal. The positive predictive value for disturbed osseous blood ßow was 96%. Conclusions: Early detection of intraosseous circulatory disturbance was possible with a mathematical model for dynamic MRI results. The method is reproducible and may be employed in the early diagnosis of AVN and during treatment for monitoration of revascularisation

1. The frequency of variable degrees of ischaemia of soft tissue in closed tibial and fibular shaft fractures is emphasised. 2. Two cases with ischaemia of calf musculature are described. 3. A follow-up study of 100 cases of closed tibial shaft fractures is analysed; ten patients were found to be affected. 4. The anatomical and pathological changes are discussed. 5. A plea is made for early surgical exploration in cases manifesting signs of ischaemia

A model of tourniquet ischaemia was developed in the hind limb of the rat, and the metabolic changes that occurred in the calf muscles were monitored by the non-invasive technique of phosphorus-31 nuclear magnetic resonance spectroscopy. During ischaemia the intramyocellular pH became acidic as the level of phosphocreatine declined and that of inorganic phosphate rose. Phosphocreatine was no longer detectable after approximately 2 hours and ATP was depleted after approximately 3.5 hours. Metabolic recovery was rapid (1 hour) if ATP was present when the tourniquet was released but was prolonged (3 or more hours) if ATP was depleted. Hourly release of the tourniquet for 10 minutes ensured the maintenance of ATP and rapid metabolic recovery. Release for intervals of only 5 minutes did not have the same protective effect and in fact worsened tissue pH during the period of tourniquet ischaemia. Heparin and corticosteroids were without effect during and after periods of tourniquet ischaemia

Purpose: Near-infrared spectroscopy (NIRS) detects changes in chromophore concentrations of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) in target tissues approximately 2 to 3 cm below the skin. The main purpose of this study was to non-invasively measure skeletal muscle oxygenation in the leg during and after tourniquet (TQ)-induced ischemia using continuous wave NIRS. Secondarily, we aimed to assess the sensitivity, specificity, and reliability of this optical technique for detection and continuous monitoring of changes in muscle oxygenation and hemodynamics during TQ-induced ischemia throughout orthopedic surgery. Method: Consented patients aged 19–69 (n=21) with unilateral ankle fracture requiring emergency or elective surgery at our institution were recruited. All patients underwent standard general anesthetic. A pair of NIRS probes was fixed over the midpoint of the tibialis anterior muscle (TA) of both the fractured and healthy legs. A thigh TQ was applied to the injured leg and inflated to 300 mmHg. Using the NIRS apparatus coupled to a laptop with data acquisition software, changes in O2Hb, HHb, and total hemoglobin (tHb) levels in the TAs of both legs were measured at 10 Hz before and during TQ inflation, and after release until values returned to baseline. In each surgery the TQ was released when arterial obstruction was no longer required by the clinical team. Data are reported as mean±SD. Results: Changes in O2Hb, HHb, and tHb were successfully collected, stored and transmitted for graphic display in all subjects. TQ time (ischemia interval) varied among subjects, from 1245 s to 4431 s (2753±854). NIRS measured a progressive increase in HHb (2.6±2 μmol/L) during the first minute of TQ inflation and a sharp increase in O2Hb (23.3±12 μmol/L) during the first minute of leg muscle reperfusion (after deflation). Following TQ inflation a progressive increase in HHb (24.2±10.3 μmol/L) with a concomitant decrease in O2Hb (mean – 24.4±8 μmol/L) in the under-TQ TA were consistent across subjects. These changes in ΔHHb and ΔO2Hb began to reverse immediately after TQ deflation. Significant correlations were observed between ischemia interval and, respectively, oxygenation recovery time (r2=0.84) and changes of deoxygenated hemoglobin (r2=0.57). Conclusion: We demonstrated that, following TQ inflation and deflation respectively, NIRS can sensitively monitor muscle deoxygenation and reoxygenation. Consistent patterns of ΔHHb and ΔO2Hb occurred during TQ-induced ischemia in all subjects. These data confirm that near infrared spectroscopy is useful for the non-invasive detection and monitoring of muscle ischemia. These results indicate that it may be useful to investigate the efficacy of NIRS in the early detection of muscle ischemia or hypoxemia in conditions such as compartment syndrome. FUNDING: MSFHR, COF, BC Lung

Tourniquet induced ischemia-reperfusion syndrome (IRS) may trigger systemic inflammatory response following a total knee arthroplasty. The IRS will be studied in a prospective randomized controlled study in humans undergoing total knee arthroplasty, by measuring blood inflammatory mediators and blood gases. Materials and Methods: Forty four (n=44) patients (female/male: 35/9 male) with a mean age of 72 years, undergoing primary total knee arthroplasty for osteoarthritis, were prospectively randomized in two groups. 22 patients operated with tourniquet [tourniquet group (TG)] and 22 patients operated without a tourniquet [non-tourniquet group (NTG)]. The mean overall ischemia time was 90 minutes. Arterial and venous blood samples were collected preoperatively, and at 1, 2, 3, 6, 24, 48 hours postoperatively. The pro-inflammatory (IL-1b, IL-6) and anti-inflammatory cytokines (IL-10) as well as the adhesion molecules (ICAM, VCAM), the CRP and blood counts were measured and correlated with the blood gases. Results: Patients in TG had higher cytokine and inflammatory mediators values, compared to the NTG group especially during the sixth postoperative hour and the first postoperative day. The most abrupt changes were evident in the patients with the highest preoperative levels of cytokines and inflammatory mediators especially when the ischemia time was more than 90 minutes. Male patients demonstrated the most significant changes. Discussion: The use of the tourniquet triggers the systemic inflammatory response. The most remarkable changes in inflammatory mediators are evident during the sixth postoperative hour and the first posoperative day. Tourniquet may be used for Total knee Replacement but care should be taken to decrease the ischemia time to the absolutely necessary specifically in males

Aims: Pharmacological modulation of skeletal muscle reperfusion injury after trauma associated ischaemia may improve limb salvage rates and prevent the associated systemic sequelae. Resuscitation with hypertonic saline restores the circulating volume and has favourable effects on tissue perfusion and blood pressure. The purpose of our study was to evaluate the effects of hypertonic saline on skeletal muscle ischaemia reperfusion (I/R) injury and the associated endorgan 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 hypertonic saline. Bilateral hind-limb ischaemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 hours. Treatment groups received either normal saline or hypertonic saline prior to tourniquet release. Following twelve hours reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Lung tissue was also harvested for measurement of wet-to-dry ratio, myeloperoxidase content and histological analysis. Results: Hypertonic saline significantly attenuated skeletal muscle reperfusion injury as shown by reduced twitch and tetanic contractions of the skeletal muscle (Table). There was also a significant reduction in lung injury as demonstrated by differences in wet-to-dry ratio, myeloperoxidase content and histological analysis. Conclusion: Resuscitation with hypertonic saline may have a protective role in attenuating skeletal muscle ischaemia reperfusion injury and its associated systemic sequelae

A series of 26 children was referred to our specialist unit with a ‘pink pulseless hand’ following a supracondylar fracture of the distal humerus after a mean period of three months (4 days to 12 months) except for one referred after almost three years. They were followed up for a mean of 15.5 years (4 to 26). The neurovascular injuries and resulting impairment in function and salvage procedures were recorded. The mean age at presentation was 8.6 years (2 to 12). There were eight girls and 18 boys. Only four of the 26 patients had undergone immediate surgical exploration before referral and three of these four had a satisfactory outcome. In one child the brachial artery had been explored unsuccessfully at 48 hours. As a result 23 of the 26 children presented with established ischaemic contracture of the forearm and hand. Two responded to conservative stretching. In the remaining 21 the antecubital fossa was explored. The aim of surgery was to try to improve the function of the hand and forearm, to assess nerve, vessel and muscle damage, to relieve entrapment and to minimise future disturbance of growth. Based on our results we recommend urgent exploration of the vessels and nerves in a child with a ‘pink pulseless hand’, not relieved by reduction of a supracondylar fracture of the distal humerus and presenting with persistent and increasing pain suggestive of a deepening nerve lesion and critical ischaemia

Peripheral limb ischaemia is rare in children. We have treated only 12 infants and children with this condition in the past 15 years at the Royal Hospital for Sick Children in Glasgow. There were nine neonates and three older children. Most were suffering from life-threatening illnesses or severe infection. Two were born with ischaemic arms with no apparent cause. We have analysed the factors leading to ischaemia, the outcome of the initial treatment and the later orthopaedic problems. Two required amputation of both legs, one of an arm, two of feet and one of toes. Two had skin grafts. All surgery was performed after demarcation was well established and delayed closure was used after amputation. Five children developed limb-length discrepancy or an angular deformity. To date two have required additional corrective surgery

A case is reported of fracture of the tibia in a haemophiliac, complicated by severe ischaemia. Extensive decompression of the limb followed later by skin grafting was required. The haematological management which made such surgery practicable is described. It involved the use of cryoprecipitate for a period of seven weeks

Introduction: Intra-uterine vascular deficiency of the upper limbs is very rare. Materials & Methods: Thirty two cases collected by 118 paediatric surgeons (GEOP) over the last 20 years were presented. Results: This series illustrates the large range of presentations of vascular deficiencies, from total ischaemia of both upper limbs to small scars of the hand. Three infants had diabetic mothers; nine children had a cerebral infarction; non disturbed haematologic screening was found; three new born had an intra-uterine thrombotic event. Discussion: Our hypothesis is that such an intra-uterine thrombotic pathology can lead to thromboembolism. The embolus passing through the foramen ovale, arrives in the high pressure circulation and is transported directly to the upper limbs and brain. The size of embolus corresponds with the extent of the necrosis

1. Volkmann's ischaemia of the lower limb is more common in adults than in children and occurs with sufficient frequency after injuries of the femur, knee and leg to warrant a more determined effort to prevent it. 2. The first and most essential step is to recognise the early signs of ischaemic damage. Incision of the deep fascia may then save the threatened underlying muscle, though it may also be necessary to seek for and evacuate a haematoma beneath the muscle. When the femoral or popliteal artery is injured, exploration and repair may be imperative. 3. The treatment of established ischaemic contracture is by whatever measures are necessary to correct the deformity. These are lengthening of shortened tendons, or excision of them if they are involved in dense fibrosis at the periphery of the ischaemic mass; and excision of all totally destroyed muscle. Amputation may be necessary

1. A bilateral case of chronic intermittent ischaemia of the soleus muscle within its fascial compartment is described in a dental surgeon aged twenty-seven. 2. Symptoms were promptly relieved by decompression. 3. The mechanism of the condition is compared with that of the anterior tibial syndrome

Introduction: Perioperative blood losses in TKR (total knee replacement) are significant and it has been determined that hidden blood loss is frequently more significant than visible blood loss. The aim of this study is to determine if there were any differences in blood loss due to the timing of ischemia cuff release during TKR. Materials and methods: We studied 103 patients divided into 2 groups; in group A, of 41 patients, the cuff was released when all the bon cuts had been carried out, hemostasis of bleeding blood vessels was carried out and pressure was elevated until the end of surgery and placement of the compressive bandage. In group B, of 62 patients, once the prosthesis was cemented the cuff was released, hemostasis was applied, the wound was sutured and the compressive bandage was put in place without elevating the cuff pressure. In both groups we recorded intraoperative blood loss, both external blood loss and through the drainage, which was removed at 36–48 hours. Hidden blood loss was determined using the formula of Naddler et al that considers sex, weight, height and preoperative hemoglobin and hemoglobin 4 days after surgery. Results: In group A the mean volume drained was 502 ml, hidden blood 928 ml, with a total loss of 1429 ml. In group B the mean volume drained was 567 ml, hidden blood 764 ml and total loss of blood 1331. There were no significant differences between both groups. Conclusions: The significance of blood loss in TKR is therefore confirmed, especially hidden blood loss. There were no statistically significant differences according to the moment at which the ischemia cuff was released

Aims: Pharmocological 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. The purpose of our study was to evaluate the effects of APC on skeletal muscle ischaemia reperfusion injury and to examine the direct effects of APC on neutrophil activation. Methods: Adult male Sprague Dawley rats (n=30) were randomised into three groups: control group, I/R group treated with normal saline and I/R treated with APC. Bilateral hind-limb ischaemia was induced by rubber ban 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, wet-to-dry ratio and histological analysis. The effect of APC on TNF-α stimulated human peripheral blood neutrophils was also examined by measuring CD 18 expression and reactive oxygen species (ROS) generation. Results: APC significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet-to-dry ratio and electrical properties of skeletal muscle. These findings were supported by our histological findings. Our in-vitro work demonstrated a reduction in CD 18 expression and ROS generation. Conclusion: Activated Protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and this is in part mediated by a direct inhibitory effect on neutrophil activation

Purpose: Several variables related to tourniquet (TQ) inflation contribute to ischemic muscle injury. Among these the duration of ischemia has been identified as a primary factor. The purposes of this study were to investigate the following during and after TQ-induced ischemia during orthopedic trauma surgery:. muscle oxygenation changes measured by near infrared spectroscopy (NIRS);. muscle protein oxidation; and. correlations between muscle oxygenation / hemodynamics and oxidative changes. Method: Consented patients aged 19–69 yrs (n=18) with unilateral ankle fracture requiring surgery at our institution were recruited. A pair of NIRS probes was fixed over the midpoint of the tibialis anterior muscle (TA) on both the injured and healthy legs. A thigh TQ was applied to the injured leg and inflated to 300 mmHg. Using the NIRS apparatus coupled to a laptop with data acquisition software, changes in oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) levels in the TA of both legs were measured before and during TQ inflation, and after release until values returned to baseline. PRE surgical biopsies were collected from the peroneus tertius muscle (PT) immediately after TQ inflation and incision. POST biopsies were collected from the same PT immediately before TQ deflation. Oxidation of PT myosin, actin, and total protein was quantified using Western blot analysis of 4-hydroxynonenal (4-HNE) modified proteins. Data are reported as mean±SD. Results: In PRE biopsies compared to POST biopsies there were large and statistically significant increases in the PT content of 4-NE modified myosin (174.4±128%; P< 1×10-6), actin (223.7±182%; P< 5×10-9), and total protein (567.5±378%; P< 5×10-7). There was a greater increase in PT protein oxidation in male subjects than in female subjects (50.8% difference; P< 0.05). In the TA of the fractured side, there were moderate to strong linear correlations between total protein oxidation and: the relative change in tHb (r=−0.704) and O2Hb (r=−0.415) during the period of TQ inflation and the rate at which the muscle became reoxygenated following TQ release (r=0.502). There was no relationship between muscle protein oxidation and TQ time, nor between muscle protein oxidation and age of patients. Conclusion: TQ-induced muscle ischemia for 21 to 74 min during lower extremity surgery leads to oxidative muscle injury as measured according to myofibrillar contractile protein oxidation. Importantly, we observed that when the TQ was “leaky,” local increases in muscle tHb were associated with a lower magnitude of protein oxidation, however, when local decreases in muscle O2Hb were observed, perhaps due to local blood loss below the TQ, more oxidative changes resulted. Intriguingly, gender appeared to influence the extent of muscle oxidative injury, but age did not. Surprisingly, there was no significant correlation between muscle oxidative injury and the TQ-induced ischemia interval. FUNDING: MSFHR, COF, BCLA