Effects of the ALX/FPR2 receptors of lipoxin A4 on lung injury induced by fat embolism syndrome in rats.

This study was designed to investigate the inflammatory responses in fat embolism syndrome (FES) and the relationship of ALX/FPR2 receptors and lipoxin A4 (LXA4) in FES models. In this model, lung injury score, lung tissue wet-to-dry (W/D) ratio and total protein concentration in bronchoalveolar lavage fluid (BALF) were increased compared with those of the control group. Meanwhile, the number of leukocytes and neutrophils was significantly increased in the FES group, as was the myeloperoxidase (MPO) activity and mRNA expression. In addition, the release of TNF-α and IL-1ß was increased. Then, we explored whether LXA4 and ALX/FPR2 were involved in the pathological process of FES. The LXA4 concentration in the experimental groups was markedly higher than that in the control group. At the same time, the protein and mRNA levels of ALX/FPR2 were upregulated in the rat model of FES. Moreover, rats treated with BML-111, an agonist for the ALX/FPR2 receptor of LXA4, showed a lower inflammatory response than mice treated with fat alone. However, the role of BML-111 in fat emboli (FE)-induced acute lung injury (ALI) was attenuated by BOC-2, an antagonist of the ALX/FPR2 receptor of LXA4. Our results demonstrated that the inflammatory response may play an important role in the pathogenesis of FES and that the activation of the ALX/FPR2 receptor for LXA4 can decrease the inflammatory response and may be a therapeutic target for FE-induced ALI.

Is lipoxin A4 an effective treatment on fat embolism syndrome by attenuating pro-inflammatory response?

Fat embolism syndrome (FES) is characterized by high mortality and lack of effective treatment, the symptomatic therapy is most used to relieve clinical symptoms. Some studies have shown that inflammation is one of the main pathogeneses of FES. Lipoxin A4 is an endogenous-derived anti-inflammatory substance which was discovered recently. It can alleviate inflammatory response and promote inflammation resolution, and is referred as brake signal of inflammation. Therefore we hypothesize that lipoxin A4 may have a remission and therapeutic effect on FES by attenuating FES-induced inflammatory responses.

Evidence for angiotensin mediation of the late histopathological effects of pulmonary fat embolism: Protection by losartan in a rat model.

PURPOSE: In a model of fat embolism using triolein-treated rats, we have reported that the acute pulmonary histopathological changes at 48 hrs were ameliorated by the angiotensin AT1 receptor blocker losartan, the angiotensin converting enzyme inhibitor captopril, and the direct renin inhibitor aliskiren. Although much of the pathology had declined by 3 weeks, the changes persisted at 6 weeks. The purpose of the study was to extends the time course investigation to 10 weeks and to examines whether the fat embolism effects continue to be blocked by losartan when given at a late time period. MATERIALS AND METHODS: Unanesthetized rats were challenged with i.v. triolein or saline. After 6 weeks, one group received saline or losartan i.p. and the losartan group also received losartan in the drinking water. At 10 weeks, the experiment was terminated. RESULTS: Confirming previous results, the fat embolism group showed normal weight gain at 6 weeks without apparent distress and also appeared normal at 10 weeks. However, at 10 weeks the lungs showed inflammatory and fibrotic changes that were greater than those found at 6 weeks. These changes were reduced by losartan. CONCLUSIONS: These findings show that the effects of fat embolism continue to progress to 10 weeks after the initial insult with triolein. The fact that the protective effects of losartan treatment started at 6 weeks supports the involvement of the renin-angiotensin system in late as well as early stages of the histopathological changes following fat embolism. It also supports the use of angiotensin blockade in clinical situations even long after an initial trauma where fat embolism is suspected.

Fat embolism: a rare cause of perioperative renal transplant dysfunction.

Fat embolism is a recognised complication of bony injury and orthopaedic surgery, commonly involving the long bones and pelvis. We report on the case of a 68-year-old renal transplant recipient who developed acute kidney injury following surgical stabilisation of metastatic carcinoma of the acetabulum and replacement of the proximal femur. A CT renal angiogram demonstrated a large fat embolus in the inferior vena cava (IVC) and left iliac veins below the level of IVC filter, with impaired renal perfusion. The risks of open or endovascular lipothrombectomy were felt to outweigh the potential benefits. The patient was managed with systemic anticoagulation and prepared for transplant failure. Subsequently, there was spontaneous improvement in urine output and 4 months postoperatively her transplant function had returned to her baseline level and this has remained stable at 1 year postsurgery.

[METABOLIC PREVENTION OF FAT EMBOLISM.]

THE AIM: to study the effect of solution with methionine "Remaxol" on metabolic disorders andfat embolism developing in severe combined trauma. MATERIALS AND METHODS: 544 patient with severe skeletal trauma were undergone to a prospective study of dynamics of fat embolism syndrome development depending on the inclusion in the program of infusion therapy drug "Remaxol". The dynamics of lactate, glucose, free fatty acids, globularia and the incidence offat embolism syndrome were analyzed. RESULTS: Corrective action drug with methionine "Remaxol" on hyperglycemia, hyperlactatemia, hyperlipemia and de- crease circulation offat globules, which is reflected in the decrease in the frequency of development offat embolism syndrome was identified. CONCLUSION: One of the proposed mechanisms reduce the risk offat embolism development is assumed restoration of endogenous carnitine synthesis with methionine and transport offree fatty acids in the cell and their subsequent inclusion in metabolic processes.

Bilateral femoral shaft fractures complicated by fat and pulmonary embolism: a case report.

A 25-year-old man was admitted to our hospital because of pulmonary embolism and suspected fat embolism after sustaining bilateral femoral shaft fracture. A left arm weakness, tachycardia and sudden hemoglobin drop delayed his definitive fixation with intramedullary nailing. His clinical course was further complicated by bleeding from the pin sites of the external fixators which had initially been used to temporarily stabilize his femoral fractures (clotting disturbances). A lower leg Doppler ultrasound and a new pelvic-chest CT angiography excluded any remaining thrombus, meanwhile the embolus had broken in smaller pieces, more distally. His unfractionated heparin was revised to a Low Molecular Weight Heparin at prophylactic dose. After a 10 day period and when his condition had been improved bilateral reamed nailing was performed. Although bilateral closed femoral shaft fractures should be stabilized early, fat embolism syndrome (FES) and thromboembolic events (TEV) should always be kept in mind in these patients.

Mitigating effects of captopril and losartan on lung histopathology in a rat model of fat embolism.

BACKGROUND: Fat embolization (FE) is an often overlooked and poorly understood complication of skeletal trauma and some orthopedic procedures. Fat embolism can lead to major pulmonary damage associated with fat embolism syndrome (FES). METHODS: A model of FE in unanesthetized rats, using intravenous injection of the neutral fat triolein, was used to study the potential therapeutic effect on lung histopathology of altering the production of, or response to, endogenous angiotensin (Ang) II. Either captopril, an Ang I converting enzyme inhibitor, or losartan, an Ang II type 1 receptor blocker, was injected 1 hour after FE by triolein injection. After euthanasia at 48 hours, histopathologic evaluation was used to compare the drug-treated animals with control animals that received only triolein. RESULTS: Histology of the lungs of rats treated only with triolein revealed severe, diffuse pathology. Alveolar septa showed severe, diffuse inflammation. Bronchial lumina showed severe mucosal epithelial loss. The media of the pulmonary small arteries and arterioles was thicker, and the lumen patency was reduced 60% to 70%. Trichrome staining confirmed the abundant presence of collagen in the media and adventitia, as well as collagen infiltrating the bronchial musculature. Both captopril and losartan treatments reduced the inflammatory, vasoconstrictor, and profibrotic effects present at 48 hours (p<0.001). With treatment, the vascular lumen remained patent, and the fat droplets were reduced in size and number. There was a reduction in the number of infiltrating leukocytes, macrophages, myofibroblasts, and eosinophils, along with a significant decrease in hemorrhage and collagen deposition (p<0.001). Pathologic changes in bronchial epithelium were also diminished. CONCLUSIONS: The results suggest that the use of drugs that act on the renin-Ang system might provide an effective and targeted therapy for fat embolism syndrome.

[Injection lipolysis]. / Injektionslipolyse.

A new treatment variation in the spectrum of aesthetic medicine has been investigated worldwide since 2004: so-called injection lipolysis. Advances in knowledge regarding the efficacy and mechanism of action have been achieved especially in Germany because most users are found in Germany when compared on an international level. The reason for this is that the combination of phosphatidylcholine and deoxycholic acid as active substances has been approved for i.v. treatment of fat embolisms. It is thus readily available, but the subcutaneous injection of the drug Lipostabil N® is considered as off-label use. Meanwhile injection lipolysis has become an integral component for many in the practice of aesthetic medicine. The international association of physicians performing lipolysis in the so-called NETWORK-Lipolysis (with more than 2,000 members worldwide) has in particular called for the development of internationally recognized treatment standards and protocols. When the indication for its use adheres to strict criteria and the physicians applying the method have participated in intensive training, subcutaneous injection of phosphatidylcholine/deoxycholic acid represents a meaningful addition to the scope of minimally invasive aesthetic medicine.

N-acetylcysteine attenuates acute lung injury induced by fat embolism.

OBJECTIVES: Fat embolism syndrome is a clinical issue in subjects with long-bone fracture. It may lead to acute lung injury. The mechanisms and therapeutic regimen remain unclear. The present study was designed to investigate the pathologic and biochemical changes after fat embolization in isolated rat lungs, and to test the effects of posttreatment with N-acetylcysteine (NAC). DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: A total of 36 perfused lungs isolated from Sprague-Dawley rats. INTERVENTIONS: The isolated lungs were randomly assigned to receive physiologic saline solution (vehicle group), fat embolism (FE group), or FE with NAC posttreatment (FE + NAC group). There were 12 isolated lungs in each group. FE was produced by introduction of corn oil micelles. NAC at a dose 150 mg/kg was given 10 mins after FE. MEASUREMENTS AND MAIN RESULTS: The extent of acute lung injury was evaluated by lung weight change, protein concentration in bronchoalveolar lavage, and exhaled nitric oxide. We also measured the pulmonary arterial pressure and capillary filtration coefficient and determined the nitrate/nitrite, methylguanidine, tumor necrosis factor-alpha, and interleukin-1beta in lung perfusate. Histopathologic changes of the lung were examined and quantified. The levels of neutrophil elastase and myeloperoxidase were determined. The expression of inducible nitric oxide synthase was detected. FE caused acute lung injury as evidenced by the lung weight changes, increases in exhaled nitric oxide and protein concentration in bronchoalveolar lavage, pulmonary hypertension, increased capillary filtration coefficient, and lung pathology. The insult also increased nitrate/nitrite, methylguanidine, tumor necrosis factor-alpha, and interleukin-1beta in lung perfusate, increased neutrophil elastase and myeloperoxidase levels, and upregulated inducible nitric oxide synthase expression. Posttreatment with NAC abrogated these changes induced by FE. CONCLUSION: FE caused acute lung injury and associated biochemical changes. Posttreatment with NAC was effective to alleviate the pathologic and biochemical changes caused by FE.

Sildenafil prevents cardiovascular changes after bone marrow fat embolization in sheep.

BACKGROUND: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated. METHODS: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg . kg . h) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat. RESULTS: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1). CONCLUSIONS: Administration of sildenafil prevented the acute cardiovascular complications after bone marrow fat embolism in sheep.

Fat embolism following posterior iliac graft harvest for jaw reconstruction: managing the complications of major surgery.

Oral and maxillofacial surgeons offer their patients a wide variety of surgical options that may be classified as major or minor surgery. Complications are part of surgery, but major surgery may lead to life-threatening complications that must be managed by the surgical team. Obtaining iliac graft tissue during oral and maxillofacial reconstruction carries the risk of rare but serious complications, such as deep vein thrombosis and fat embolism syndrome. In this paper we describe the latter postoperative complication experienced by a patient undergoing an otherwise routine major oral and maxillofacial reconstructive procedure. A discussion of the factors that stimulate fat embolism during or following surgical procedures is intended to help surgeons prevent this complication.