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.

[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.

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.

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.

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.

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.

[Fat embolism and syndrome of pleural effusion].

Authors present the frequency, pathological disorders and consequences of fat microembolia of the lung. Peculiarities of fat embolia in patients with blunt traumas of the foot and shin were shown in the article. Rare cases (2) of SPE manifestation in patients with fat embolia of the lung, experience of pathogenetic therapy of complications and recommendations regarding diagnostics of complications in patients with this disease are given in the article.

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.

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.

Fat embolism and the fat embolism syndrome. A double-blind therapeutic study.

Fifty-five adults who had sustained a tibial fracture, or a femoral fracture, or both, were subjected to a double-blind randomised study to determine the efficacy of methylprednisolone in treating the fat embolism syndrome. This drug maintained arterial oxygen levels, stabilised or reduced the serum level of free fatty acids, and decreased the risk of the fat embolism syndrome in a statistically significant proportion of patients. Gurd's criteria for the diagnosis of the fat embolism syndrome were found inadequate. Other more sensitive criteria for early diagnosis and effective management were determined. There were no deaths or serious morbidity in our series.

Experimental study of early diagnosis and treatment of fat embolism syndrome.

An experimental animal model has been established using i.v. fat injection to mimic fat embolism syndrome (FES). Fourteen healthy mongrel dogs who were administered 0.7 ml/kg of fluid marrow fat obtained from the long bone marrow cavity of mongrel dogs were divided into control and therapeutic groups. The therapeutic group (n = 7) was given dexamethasone (1.0 mg/kg) and repeated every 6 h i.v. During 48 h of observation, blood gas analysis and frozen sections were performed on blood samples collected from the pulmonary vessels by a floating catheter and from a peripheral vein at different time intervals. The frozen sections were stained with Oil Red O. Positive results were seen 2 h after fat injection in both pulmonary and peripheral blood samples of both control and therapeutic groups. By computer image analysis, the average median number of fat droplets per section and the average median diameter of fat droplets in pulmonary blood of the control group were found to be significantly higher and larger than were those of the therapeutic group. The average median number and diameter of fat droplets in pulmonary blood were significantly higher and larger than were those of peripheral blood in both control and therapeutic groups. These findings correlated well with blood gas changes and the clinical appearance of the experimental animals. The fat droplets from pulmonary or peripheral blood as demonstrated by Oil Red O staining in combination with blood gases changes [PaO2 < 7.99 KPa, difference between the alveolar and arterial oxygen tension (P(A - a)O2) > 6.09 KPa] may be a rapid method for screening of an earlier diagnosis of FES.(ABSTRACT TRUNCATED AT 250 WORDS)

The utility of parenteral glucocorticoids in the emergency department.

Exogenous glucocorticoids have wide clinical applicability in emergency medicine. Many uses reported for this class of drugs are supported by only anecdotal evidence of efficacy, while others have been proven or disproven by well-designed studies; this evidence is evaluated here. Because adverse effects are relatively common and may be serious after initiation of steroid therapy in the emergency department, it is important for the emergency physician to review systematically the indications, contraindications, and precautions for the use of parenteral glucocorticoids.

Hemodynamic changes in pulmonary circulation following fat embolism.

Hemodynamic effects in pulmonary circulation were measured in three young patients having proved fat embolism following trauma. The increase of pulmonary artery pressure, even in the early phase, was typical. The direction of the therapy to normalise the hemodynamic changes was the most important part of the therapeutic management.

Severe fat embolism: a review of 24 cases.

Twenty-four patients suffering from fat embolism syndrome, severe enough to warrant transfer to an artificial ventilation unit, are reviewed. All developed the condition following trauma. Five patients were managed with oxygen therapy and sedation, but the other 19 needed intubation and ventilation to achieve adequate arterial oxygenation. In spite of intensive supportive therapy, 6 patients (who had all required ventilation) died, one due to heparin therapy, the others from progression of the syndrome. A poor prognosis seemed to be associated with young age, a rapidly progressive condition and a continued need for 100 per cent oxygen after institution of artificial ventilation. There seemed to be no relationship between outcome and severity of injury, type of surgical management and time of onset after injury. The clinical features of these patients are discussed with reference to the many unanswered questions that surround this condition.

Fat embolism syndrome following long bone fractures.

During the period August, 1979 to December, 1992, 14 patients with the Fat Embolism Syndrome (FES) were admitted to the University Hospital of the West Indies (UHWI). Two were females and 12 males, their ages ranging from 18 to 78 years, with a median age of 23.5 years. All had lower limb long bone fractures. Clinical features included fever, tachypnoea, confusion and drowsiness. They were all hypoxaemic; 9 required Intensive Care Unit (ICU) admission and, of these, 4 needed ventilatory support. Five patients became comatose, 4 of whom developed decerebrate posturing. There was one death from Klebsiella septicaemia, and 13 patients recovered fully. The FES is a serious life-threatening complication of long bone fractures whether simple or compound, usually occurring within 72 hours of the injury. A high index of suspicion is needed for its prompt detection, and early attempts at maintaining adequate tissue oxygenation must be instituted if serious neurological complications and death are to be avoided.