triolein and Embolism--Fat

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.. 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.. 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.. 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.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Embolism, Fat; Losartan; Lung Diseases; Rats; Renin-Angiotensin System; Time Factors; Triolein

Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, captopril and losartan reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model.. The FE model used intravenous injection of the neutral fat triolein in unanesthetized rats. Intraperitoneal injections of saline or aliskiren at either 50 or 100 mg/kg were performed 1 hour after FE induction via triolein. Rats were euthanized at 48 hours, and various histologic stains were used to examine the lungs.. (1) Fibrosis: rats treated with triolein showed significant fibrotic changes with increased collagen and myofibroblast activation (p < 0.0001 for both trichrome and α-smooth muscle actin staining). Aliskiren blocked this inflammatory and profibrotic process to a level indistinguishable from the controls (p < 0.0001 for both trichrome and α-smooth muscle actin staining). (2) Fat: rats treated with triolein showed a statistically significant increase in fat (p = 0.0006). Subsequent aliskiren administration at both doses reduced the size, distribution, and amount of fat droplets (low dose, p = 0.0095; high dose, p = 0.0028). (3) Vessel patency: the low dose of aliskiren blocked the reduction of lumen patency observed after triolein administration (p = 0.0058).. Aliskiren protected the lungs of rats from gross and histopathologic FE-induced pulmonary damage at 48 hours. Clinical implications include the use of aliskiren both prophylactically (before certain orthopedic procedures) and therapeutically (after severe trauma) to prevent the consequent severe pulmonary pathologic sequelae.

Topics: Amides; Animals; Disease Models, Animal; Embolism, Fat; Fumarates; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Triolein

Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time, an additional insult could exacerbate the effects.. Triolein (0.2 mL intravenously administered) was given to 18 rats and saline to 18 controls. Six weeks later, each group received (intraperitoneal) lipopolysaccharide (LPS, 3 mg/kg; n = 9) or saline (n = 9). At necropsy 48 hours later, lungs and organs were harvested for study. Lung parenchymal, vascular, and bronchial damage was scored by two pathologists and by Image J analysis.. Animals given LPS after triolein showed reduced pulmonary arterial medial diameters compared with those that received LPS alone (p < 0.04). Lung small arterial patency (lumen) was reduced after triolein and even more after combined LPS and triolein (p = 0.018). Triolein increased fibrotic markers (trichrome and smooth muscle actin staining), and this was more severe after LPS. At 6 weeks, fat droplets remained in the lungs, localizing to the subpleural septa. These were smaller and more widespread after LPS.. This report describes an animal model to study exacerbation of lung histopathology induced by FE using a known pulmonary toxicant, LPS (a "second hit"). Vascular and fibrotic lung damage was more severe when LPS was given to rats 6 weeks after triolein compared with LPS alone. FE rendered the lungs extra sensitive to a second hit long after apparent clinical recovery. This experimental model of fat embolism provides useful informations for the treatment of patients suffering for similar conditions.

Topics: Animals; Disease Models, Animal; Embolism, Fat; Lipopolysaccharides; Male; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Triolein; Vascular Patency

Hemorrhage is a finding of clinical fat embolism syndrome. The purpose of the present study was to evaluate the occurrence of hemorrhage in the cat brain by SW MR imaging after infusion of triolein as a bolus or as an emulsion into the carotid artery.. Twenty-two cats were divided into two groups according to the type of triolein infused: group 1 (n = 11) was infused with a 0.1 ml triolein bolus, group 2 (n = 11) with triolein emulsion containing 0.1 ml triolein in 20 ml saline. SW imaging was performed before and after triolein infusion (at 2 h, 1 and 4 days). After MR imaging on day 4, cats were sacrificed and brains were immediately excised. Hemorrhage was evaluated using H&E staining.. Hemorrhage was observed in eight cats in group 1, in no cats in group 2. Hemorrhage on SW images was found to correspond with light microscopy.. SW images revealed hemorrhage in lesion hemispheres infused with triolein bolus. However, there was no evidence of hemorrhage infused with emulsified triolein. Thus, the occurrence of hemorrhage in cerebral fat embolism may depend on fat status.

Topics: Animals; Cats; Cerebral Hemorrhage; Disease Models, Animal; Embolism, Fat; Fat Emulsions, Intravenous; Intracranial Embolism; Magnetic Resonance Imaging; Triolein

Lipid embolizations from retransfused shed blood during cardiac surgery have been shown to enter the circulation and end up in different organs. The purpose of this investigation was to evaluate differences in the kinetics and deposition between emulsified and non-emulsified lipid emboli in a porcine model.. Twelve animals were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom (6 animals given emulsified and 6 given non-emulsified lipids) was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Arterial and venous blood samples were taken at short intervals. Tissue samples were taken post-mortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used to measure lipid emboli content in blood and tissue.. Emulsified lipid emboli generated a 5-fold higher embolic load in the arterial and a 12-fold higher in the venous circulation, compared with non-emulsified lipid emboli. Emulsified lipid micro emboli resulted in a 2-15-fold higher tissue deposition in investigated organs compared with non-emulsified lipid micro emboli.. This study shows that the state of emulsion significantly alter the kinetics and tissue deposition of lipid emboli. Emulsified lipid emboli give higher embolic load in the arterial and venous circulation, and higher tissue deposition versus non-emulsified lipid emboli. In both groups, the embolic load was higher in the arterial circulation than on the venous side.

Topics: Animals; Cardiopulmonary Bypass; Disease Models, Animal; Embolism, Fat; Lipids; Radiopharmaceuticals; Swine; Triolein; Tritium

The purpose of this study is to investigate immediate changes in the blood retinal barrier (BRB) after the infusion of triolein emulsion.. Triolein emulsion was infused into the carotid artery of 12 cats to induce experimental fat embolism. The injection of fluorescein dye into the carotid artery followed immediately. Early retinal vascular flow was recorded by a fluorescein angiography (FA) video, and then a FA photograph was obtained up to 30 min after the injection. Leakage of the dye in the choroidal or retinal vessels was evaluated.. In the early phase, multifocal non-perfuse areas were noted in all cats due to embolism by triolein emulsion, which was released by blood perfusion in the late phase. Perfusion defects persisted in the retina of five cats and in the choroid of four cats. Leakage of the dye through the retinal vessels was seen in five cats (42%) in the early phase and in nine cats (75%) in the late phase. In the choroid, leakage of the dye was seen in seven cats (58%) in the early phase and in all cats (100%) in the late phase.. The inner and outer BRB was opened immediately after infusion of triolein emulsion into the carotid artery. Embolism by triolein emulsion was readily resolved due to the liquid nature of triolein.

Topics: Animals; Blood-Retinal Barrier; Capillary Permeability; Carotid Arteries; Cats; Choroid; Choroid Diseases; Embolism, Fat; Emulsions; Fluorescein Angiography; Infusions, Intra-Arterial; Ophthalmoscopy; Retinal Diseases; Retinal Vessels; Triolein

Fat embolism syndrome is a serious complication observed after trauma, orthopedic surgery, and cardiac surgery. We investigated brain damage in relationship to temporal profiles of water channel aquaporin 4 (AQP4) and astrocyte response to fat embolism in rats.. Triolein (2 microl) was injected into the right internal carotid artery in rats. Neurological outcome (score: range, 0-5 = no deficit-dead), brain water content, histopathology, and immunohistochemistry for AQP4 and glial fibrillary acidic protein (GFAP) were evaluated at 2 h (2 h group, n = 12), 24 h (24 h group, n = 12), and 72 h (72 h group, n = 12) after triolein injection. Saline was injected in the control (C) group (n = 12).. Neurological deficit score (median score of 2) and brain water content (mean value, 86.2%) increased significantly at 2 h with no progressive increase over 72 h. Damaged tissues with shrunken and triangular-shaped neurons with vacuole degeneration in cytoplasm and halo formation were distributed mainly, but not exclusively, to the ipsilateral hemisphere and were associated with increase in infiltration of inflammatory cells during the time course. Increases in immunostaining for AQP4 and GFAP were observed in the peri-affected region but not in the core. Reactive astrocytes with hypertrophy and dendrite elongation were detected at 72 h in the peri-affected region.. The results suggest that brain damage with edema is induced very rapidly after triolein injection in association with increase in AQP4 expression and GFAP in the peri-affected region.

Topics: Animals; Aquaporin 4; Astrocytes; Brain; Disease Models, Animal; Embolism, Fat; Glial Fibrillary Acidic Protein; Male; Random Allocation; Rats; Rats, Wistar; Triolein

Triolein emulsion is under investigation for supplemental use to open the blood-brain barrier during chemotherapy. The effects of triolein emulsion on the blood-retinal barrier (BRB) were investigated.. Fat emboli were induced in 20 cats by injecting triolein emulsion through the carotid artery. At 30 min, 4, 12 and 48 h after embolization, electroretinography (ERG) and fluorescein angiography (FA) were performed. The eyeballs were enucleated for transmission electron-microscopic study.. FA revealed multiple leaking points at 30 min, and prominent diffuse leakage at 4 h when scotopic b-waves showed significant differences between the study and control eyes. Multiple focal disruptions of the blood vessels by fat vacuoles were found with electron microscopic study. ERG improved at 12 and 48 h, and the BRB appeared to be recovered on FA and electron microscopic studies after 48 h.. An experimental embolism with triolein emulsion disrupted the blood retinal barrier. Delayed maximal change was observed, and it could be implicated in the latent interval of clinical fat embolism syndrome.

Topics: Animals; Blood-Retinal Barrier; Capillary Permeability; Cats; Dark Adaptation; Disease Models, Animal; Electron Microscope Tomography; Electroretinography; Embolism, Fat; Emulsions; Eye Diseases; Fluorescein Angiography; Time Factors; Triolein

To study the kinetics of lipid micro-emboli during cardiac surgery.. Eleven pigs were studied. Seven of these were put on extracorporeal circulation. A shed blood phantom consisted of blood, saline and radioactive triolein was added to the circuit. Both venous and arterial blood samples were taken at short intervals. Four animals were used to study renal kinetics without extracorporeal circulation. The same kind of shed blood phantom was infused into the ascending aorta. Samples were taken from the renal artery and vein. All samples were analyzed for radioactivity by scintillation counting.. A median 130-fold increase in radioactivity was seen in the blood and was quickly eliminated. Systemic first-pass wedging was found to be 62%. The first-pass elimination in the kidney was 77%. No radioactivity was found in urine.. This study shows that the turnover of lipid micro-emboli is fast, and that the majority of the emboli are trapped on their first passage through the capillary system. No evidence was found of a renal excretion of these lipid emboli.

Topics: Animals; Aorta; Blood Pressure; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Disease Models, Animal; Embolism, Fat; Kidney; Phantoms, Imaging; Radiopharmaceuticals; Regional Blood Flow; Renal Circulation; Scintillation Counting; Swine; Triolein; Tritium

In experimental studies, embolization of the cerebral hemisphere with triolein emulsion has revealed reversible magnetic resonance imaging (MRI) findings in the subacute stage.. To investigate the changes in the major metabolites, by proton magnetic resonance spectroscopy (MRS), in a cerebral fat embolism induced by a triolein emulsion.. The internal carotid arteries of 19 cats were injected with a triolein emulsion, and multivoxel MRS was performed 30 min, 1 day, and 7 days later. In the control group, six cats were injected with normal saline. The MR spectra were evaluated for N-acetyl aspartate (NAA), creatine (Cr), and choline (Cho), along with the presence of lipid and lactate. Semiquantitative analyses of NAA/Cr, Cho/Cr, NAA/Cho, and lipid/Cr ratios compared the median values of the ipsilateral metabolite ratios with those of the contralateral side and in the control group for each point in time.. The NAA/Cr, Cho/Cr, and NAA/Cho ratios in the ipsilateral cerebral hemisphere of the embolized group after 30 min, 1 day, and 7days were not significantly different from the contralateral hemisphere of the embolized and control groups (P>0.05). The lipid/Cr ratio in the ipsilateral cerebral hemisphere of the embolized group was significantly higher when compared with the control group (P=0.012 at 30 min, P=0.001 on day 1, and P=0.018 on day 7).. Cerebral fat embolism induced by a triolein emulsion resulted in no significant change in the major metabolites of the brain in the acute stage, except for an elevated lipid/Cr ratio, which suggests the absence of any significant hypoxic-ischemic changes in the lesions embolized using a fat emulsion.

Topics: Animals; Aspartic Acid; Brain; Cats; Choline; Contrast Media; Creatine; Disease Models, Animal; Disease Progression; Embolism, Fat; Follow-Up Studies; Gadolinium DTPA; Image Enhancement; Intracranial Embolism; Lactic Acid; Lipid Metabolism; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Sodium Chloride; Triolein

The relationship between the volume of fat flowing in the bloodstream and the degree of pulmonary fat embolism has remained unclear. In this study, in order to examine whether the volume of fat particles in the bloodstream could be estimated from the degree of pulmonary fat embolism, 0.05, 0.1, 0.15, 0.2 and 0.25 ml of triolein were injected into male rats weighing 300-320 g, through the caudal vein. Consequently, it was noted that the severity of pulmonary fat embolism tended to gradually increase in proportion to the volume of injected triolein, with the severity of pulmonary fat embolism being significantly augmented by the injection of 0.2 and 0.25 ml of triolein, based on morphometric analysis. In application to human cases, about 60 ml of fat particles was estimated to flow into the bloodstream after the occurrence of a pelvic fracture. Moreover, the results of this study led to the hypothesis that the prognosis of pulmonary fat embolism is affected by the severity of preceding conditions which have caused fat embolism.

Topics: Animals; Cerebrum; Dose-Response Relationship, Drug; Embolism, Fat; Forensic Pathology; Injections, Intravenous; Kidney; Lung; Male; Microscopy; Pulmonary Embolism; Rats; Rats, Wistar; Severity of Illness Index; Triolein

Lipid microemboli found in shed blood during cardiac surgery have been shown to block capillaries of the brain postoperatively. In this study, the distribution of lipid microemboli in different regions of the brain and other organs was examined. A novel porcine model using radioactive lipid particles was used.. Ten animals (2 controls and 8 cases) were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Tissue samples were taken postmortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used as a measure of the uptake of lipid microemboli.. High levels of radioactivity were found in kidney and spleen (5 to 10 times higher than in the other organs investigated). In the brain, radioactivity was found in all regions examined. The gray matter of cerebrum showed the highest level of the regions examined.. This study shows that embolization of lipids is not a phenomenon restricted to the brain, but affected all the organs examined. The high levels found in the kidneys, and the relatively high levels in the gray matter of the cerebrum further legitimize the debate on the impact lipid microemboli has on postoperative kidney and cognitive dysfunction.

Topics: Animals; Brain; Cardiopulmonary Bypass; Disease Models, Animal; Embolism, Fat; Kidney; Lipid Metabolism; Spleen; Swine; Tissue Distribution; Triolein; Tritium

Topics: Animals; Brain; Cardiopulmonary Bypass; Dogs; Embolism, Fat; Filtration; Kidney; Particle Size; Reproducibility of Results; Spleen; Swine; Tissue Distribution; Triolein; Tritium

The purpose of this study was to evaluate the cerebral hemodynamic change in the hyperacute stage of cerebral fat embolism induced by triolein emulsion, by using MR perfusion imaging in cat brains.. By using the femoral arterial approach, the internal carotid arteries of 14 cats were infused with an emulsion of triolein 0.05 mL. T2-weighted (T2WI), diffusion-weighted (DWI), apparent diffusion coefficient (ADC) map, perfusion-weighted (PWI), and gadolinium-enhanced T1-weighted (Gd-T1WI) images were obtained serially at 30 minutes and 2, 4, and 6 hours after infusion. The MR images were evaluated qualitatively and quantitatively. Qualitative evaluation was performed by assessing the signal intensity of the serial MR images. Quantitative assessment was performed by comparing the signal-intensity ratio (SIR) of the lesions to the contralateral normal side calculated on T2WIs, Gd-T1WIs, DWIs, and ADC maps at each acquisition time and by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (CBF), and mean transit times (MTT) of the lesions to the contralateral normal side calculated on PWI.. In the qualitative evaluation of the MR images, the lesions showed hyperintensity on T2WIs, enhancement on the Gd-T1WIs, and isointensity on DWIs and the ADC maps. In the quantitative studies, SIRs on the Gd-T1WIs, DWIs, and ADC maps peaked at 2 hours after infusion. The SIRs on the T2WIs peaked at 4 hours after infusion and decreased thereafter. On PWIs, the rCBV, rCBF, and MTT of the lesion showed no significant difference from the contralateral normal side (P = .09, .30, and .13, respectively) and showed no significant change of time course (P = .17, .31, and .66, respectively).. The embolized lesions induced by triolein emulsion showed no significant difference in cerebral hemodynamic parameters from those on the contralateral normal side. The result may suggest that consideration of the hemodynamic factor of embolized lesions is not necessary in further studies of the blood-brain barrier with triolein emulsion.

Topics: Acute Disease; Animals; Blood Flow Velocity; Blood Volume; Cats; Cerebral Cortex; Contrast Media; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Dominance, Cerebral; Embolism, Fat; Fat Emulsions, Intravenous; Hemodynamics; Image Enhancement; Intracranial Embolism; Magnetic Resonance Angiography; Regional Blood Flow; Triolein

In fat embolism, free fatty acid is more toxic than neutral fat in terms of tissue damage. We evaluated the hyperacute embolic effects of triolein and oleic acid in cat brains by using MR imaging and electron microscopy.. T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging were performed in cat brains after the injection of triolein (group 1, n = 8) or oleic acid (group 2, n = 10) into the internal carotid artery. MR images were quantitatively assessed by comparing the signal intensity ratios of the lesions with their counterparts on T2-weighted images, apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted images. Electron microscopic findings in group 1 were compared with those in group 2.. Qualitatively, MR images revealed two types of lesions. Type 1 lesions were hyperintense on diffusion-weighted images and hypointense on ADC maps. Type 2 lesions were isointense or mildly hyperintense on diffusion-weighted images and isointense on ADC maps. Quantitatively, the signal intensity ratios of type 1 lesions in group 2 specimens were significantly higher on T2-weighted images (P =.013)/(P =.027) and lower on ADC maps compared with those of group 1. Electron microscopy of type 1 lesions in both groups revealed more prominent widening of the perivascular space and swelling of the neural cells in group 2, in contrast to notable endothelial defects in group 1.. MR and electron microscopic data on cerebral fat embolism induced by either triolein or oleic acid revealed characteristics suggestive of both vasogenic and cytotoxic edema in the hyperacute stage. Tissue damage appeared more severe in the oleic acid group than in the triolein group.

Topics: Animals; Brain; Cats; Contrast Media; Diffusion Magnetic Resonance Imaging; Embolism, Fat; Intracranial Embolism; Magnetic Resonance Imaging; Microscopy, Electron; Oleic Acid; Triolein

Pathophysiologic mechanisms of the fat embolism syndrome are poorly understood. Neutrophils are thought to play a role in the development of many forms of acute lung injury. The objective of this study was to examine the role of intrapulmonary neutrophils in lung injury resulting from fat infusion.. Triolein (0.08 mL/kg) was infused into isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pulmonary arterial pressure was monitored, and pulmonary vascular resistance and microvascular permeability (Kf) were measured at baseline and 60 minutes after triolein infusion.. Triolein produced increases in pulmonary arterial pressure, pulmonary vascular resistance, and Kf. Neutrophil depletion or inhibition of neutrophil elastase prevented the increase in Kf after triolein, and catalase partially blocked this Kf increase.. These results suggest that activated intrapulmonary neutrophils play a major role in developing triolein-induced lung injury, intrapulmonary neutrophils act chiefly via neutrophil elastase release, and reactive oxygen species are involved in the lung injury.

Topics: Animals; Blood Pressure; Capillary Permeability; Disease Models, Animal; Embolism, Fat; Hemodynamics; Lung; Microcirculation; Neutrophils; Peroxidase; Rabbits; Respiratory Distress Syndrome; Triolein; Vascular Resistance

The pathophysiologic mechanism of the fat embolism syndrome is poorly understood. This study was designed to determine the effects of fat emboli on pulmonary vasculature.. Triolein was infused into isolated rat lungs perfused with Krebs-Henseleit buffer. Pulmonary arterial pressure and microvascular permeability (Kf) were measured at baseline and 20 minutes after the triolein infusion.. The 99% triolein produced dose-dependent increases in both pulmonary arterial pressure and Kf. The 65% triolein, containing free fatty acid, resulted in a greater increase in Kf. Pretreatment with indomethacin attenuated the increase in Kf after 65% triolein but not after 99% triolein.. Pure triolein induced mainly embolization in the pulmonary vasculature, and 65% triolein caused embolization and subsequently increased vascular permeability, which are, at least in part, mediated by the action of cyclooxygenase products. Free fatty acids might induce permeability edema by means of a cyclooxygenase-dependent mechanism. We conclude that triolein-induced increases in pulmonary arterial pressure and Kf in isolated rat lungs provides a useful model of acute lung injury by fat embolism.

Topics: 1-Methyl-3-isobutylxanthine; Animals; Blood Pressure; Capillary Permeability; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Embolism, Fat; In Vitro Techniques; Indomethacin; Lung; Male; Microcirculation; Muscle, Smooth, Vascular; Phosphodiesterase Inhibitors; Pulmonary Artery; Pulmonary Circulation; Pulmonary Embolism; Rats; Rats, Wistar; Respiratory Distress Syndrome; Triolein; Vascular Resistance

This study was designed to determine the distribution of fat which reaches the brain by the internal carotid artery, and the consequent alterations in the blood brain barrier, in a rat model of cerebral arterial fat embolism. The distribution of the blood flow in this model was determined by the injection of radiolabelled microspheres. Over 44% were trapped in the brain, 43% in the extracerebral tissues of the head and neck, and 7% in the lungs. Over 30% of radiolabelled triolein was present within the brain 30 min after injection, and 4% still remained after 17 days. Approximately 25% of the triolein which went to the brain moved through the cerebral vessels and left within the first 15 min. The majority of the triolein distributed to the ipsilateral cerebral hemisphere, with significantly less to the contralateral cerebral hemisphere, brain stem and cerebellum. The blood brain barrier opened, as measured by uptake of 99mTc, within the first 15 min and remained open for at least 3 days. A significant percentage of fat reaching the brain persists for days, and causes rapid and long-lasting damage to the blood brain barrier.

Topics: Animals; Blood-Brain Barrier; Carotid Artery, Internal; Disease Models, Animal; Embolism, Fat; Fats; Injections, Intra-Arterial; Intracranial Embolism and Thrombosis; Microspheres; Rats; Rats, Wistar; Tissue Distribution; Triolein

Pulmonary fat embolism occurs frequently after trauma but its functional significance is often unclear. To obtain direct evidence of lung damage caused by fat embolism we have measured changes in permeability of the alveolar-capillary interface. A permeability index was derived from the half time clearance from lung to blood (T1/2LB) of 99mTcDTPA introduced into the lung in a 1 ml bolus. Three groups of rabbits were studied. Baseline T1/2LB. did not differ significantly between groups. After intravenous injection of saline placebo in one group and of 300 mg/kg triolein in another group there was no change in permeability index. After intravenous injection of 100 mg/kg oleic acid in the third group there was an immediate change in T1/2LB from a monoexponential baseline 280 +/- 20 min (SEM) to a multiexponential curve which was resolved into two components, one with a T1/2LB of 3.2 +/- 0.6 min (SEM) and the other 39.5 +/- 7.6 min (SEM). Statistically significant changes in alveolar-arterial PO2 difference, dynamic compliance, chest radiography, and postmortem lung water accompanied the changes in T1/2LB in this group. There were no significant changes in these variables in the placebo or triolein group. Histological studies of the lung tissue of these animals using the osmic acid stain for fat showed no fat in the placebo group, extensive fat embolisation which was densely stained in the triolein group and much less densely stained fat in the oleic acid group. Measurement of the permeability of the alveolar-capillary interface provides direct evidence of lung damage after oleic acid embolisation. There were no functional changes in animals with extensive embolisation with triolein.

Topics: Animals; Capillary Permeability; Embolism, Fat; Epithelium; Lung; Oleic Acid; Oleic Acids; Pulmonary Alveoli; Pulmonary Embolism; Rabbits; Triolein

Twenty-two adult dogs were each given a single, 30-minute injection of 1.5 ml/kg body weight of pure triolein, and their pulmonary, hepatic, renal, and cerebral morphology was observed for 1, 2, 3, 4, 5, 6, 15, 24, and 48 hours; 3,4, and 5 days; 1 and 2 weeks; and 1 month after the injection. A picture of massive capillary occlusion by lipid droplets was followed by rapidly resolvable inflammatory pneumopathy of granulomatous type, leaving a normal lung at the end of the experiment. The cleaning of the capillaries may be attributed to the mechanical action of the blood flow and to the inflammatory reaction with evacuation of necrotic cells via the bronchial route. Transient pulmonary edema is attributed to increased pulmonary arterial pressure. There was no intravacular coagulation. The few pulmonary lesions observed after the triolein injection suggest that the chemical theory of neutral fat hydrolysis by pulmonary lipase and the toxicity of free fatty acids that are released should be reconsidered.

Topics: Animals; Brain; Dogs; Embolism, Fat; Kidney; Liver; Lung; Lung Diseases; Time Factors; Triolein

Pulmonary haemodynamic and arterial blood gas changes were measured in dogs subjected to either an intravenous injection of triolein or external trauma, which produced fractures of the ipsilateral femur, tibia and fibula. Musculoskeletal trauma resulted in pulmonary vasoconstriction followed by vasodilatation, arterial hypoxia with a pulmonary shunt of 30% and a 20% decrease in systemic oxygen delivery. Lipid injection produced an increased pulmonary vascular resistance, but no significant hypoxia, pulmonary shunting or inadequate tissue oxygenation. We therefore suggest that pulmonary fat embolism does not account for the pulmonary insufficiency following musculoskeletal trauma.

Topics: Animals; Blood Gas Analysis; Dogs; Embolism, Fat; Femoral Fractures; Fibula; Fractures, Bone; Fractures, Closed; Hemodynamics; Muscles; Pulmonary Valve Insufficiency; Respiratory Insufficiency; Tibial Fractures; Triolein

In human fat embolism we often find different grades of changes in both eyes of a patient. This was experimentally verified in rabbits. The anesthetized animals were held in lateral position so that one eye was continuously higher than the other. Labelled fat was injected intravenously, and then the activity in each eye was measured by a scintillation-counter. By this method a significantly higher rate of fat embolism was found in the upper eye.

Topics: Animals; Embolism, Fat; Eye Diseases; Female; Gravitation; Iodine Radioisotopes; Male; Rabbits; Scintillation Counting; Triolein

The intravenous injection of triolein in the rabbit, besides general consequences in some viscera (functional ischemic necrosis of the right ventricle, systemic cerebral and kidney embolisms), induces in the lung non specific reactions similar to those observed after other pulmonary agressions. Yet, some peculiarities are observed only in this experimental model: severe and persistent septal oedema due to early endothelial changes; intensive inflammatory response with numerous macrophages. On the other hand, except in zones with epithelio-conjonctive repair process of necrotic foci, the epithelial reaction reduced to a temporary predominance of type 2-pneumonocytes, remains of low intensity.

Topics: Animals; Disease Models, Animal; Edema; Embolism, Fat; Inflammation; Kidney Glomerulus; Lung; Rabbits; Time Factors; Triolein

Injection 125I-glyceryl trioleate (0-5 mg/kg) into the right atrium of anaesthetized greyhounds caused the following changes: sequestration of far in the right side of the heart; 95 per cent removal by the lungs in a single passage through the pulmonary circulation; subsequent release of fat into the systemic circulation; rapid overall turnover of fat trapped in the lungs and slow removal of recirculating fat by other tissues. We believe that if there is release of unemulsified fat into the circulation in traumatic fat embolism these findings are of significance in interpreting the subsequent pulmonary events.

Topics: Animals; Dogs; Embolism, Fat; Fats, Unsaturated; Lung; Time Factors; Triolein

Glyceryl trioleate has been injected into greyhounds as a model of the fat embolism syndrome. Pulmonary vascular pressures, systemic arterial pressure and cardiac output were determined at regular intervals over an 8-hour period. It has been shown that glyceryl tioleate causes an increased pulmonary vascular resistance and a fall in cardiac output. These effects are mediated partly by a direct mechanical block of pulmonary vessels and partly through a thrombogenic property of the injected fat. The relevance of these findings to the clinical situation is discussed and a sequence of events for the fat embolism syndrome is proposed.

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Embolism, Fat; Hypoxia; Lung; Myocardium; Pulmonary Artery; Time Factors; Triolein; Vascular Resistance

Pulmonary embolism was produced in rabbits by the intravenous injection of 0-5 ml/kg body-weight of glycerol trioleate and mineral oil. Lung weight, pulmonary total lipid, esterified and free fatty acids content increased in both groups, but the concentration of free fatty acids increased only in the animals injected with neutral fat. Mineral oil injection produced stasis and haemorrhage; neutral fat produced exudation of serous liquid into the alveoli and an inflammatory reaction. There are definite differences between the pulmonary effects of mineral oil embolism and neutral fat embolism. The observations support the assumption that pulmonary changes in fat embolism are due to the toxic effect of free fatty acids liberated from the embolized neutral fat.

Topics: Animals; Embolism, Fat; Fatty Acids, Nonesterified; Lipid Metabolism; Lung; Mineral Oil; Organ Size; Pulmonary Embolism; Rabbits; Triolein

Topics: Animals; Carbon Radioisotopes; Disease Models, Animal; Embolism, Fat; Glycosaminoglycans; Heparin; Heparitin Sulfate; Injections, Intravenous; Lipase; Lung; Mice; Pulmonary Embolism; Triolein

Topics: Animals; Dogs; Embolism, Fat; Lung; Respiratory Distress Syndrome; Triolein

In considering intravenous injection of lipid as a model of fat embolism, contamination is frequent and purity must be demonstrated. Musculoskeletal trauma causes mild arterial hypoxia whereas intravenous pure triolein 0.1 mg/kg does not. Trauma produced a leukocytosis and elevated sedimentation rate not found in the lipid injected dogs. Evidence for consumptive coagulopathy was found in the trauma group but only a mild thrombocytopenia resulted from intravenous triolein. The traumatized dogs demonstrated an increase in the triglyceride level, an increase in the cholesterol phopholipid ratio and an increase in the cholesterol containing beta and prebeta lipoprotein fractions, all of which could lead to formation of pulmonary fat emboli containing cholesterol.

Topics: Animals; Cholesterol; Consummatory Behavior; Disease Models, Animal; Dogs; Embolism, Fat; Hindlimb; Leukocytosis; Lipid Metabolism; Thrombocytopenia; Triglycerides; Triolein; Wounds and Injuries

The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause.

Topics: Acute Disease; Animals; Blood; Blood Circulation; Blood Pressure; Carbon Dioxide; Carbon Radioisotopes; Dogs; Embolism, Fat; Hydrogen-Ion Concentration; Hypertension, Pulmonary; Hypoxia; Liver; Lung; Pulmonary Circulation; Respiration; Triolein

Topics: Animals; Blood Vessels; Embolism, Fat; Fibrin; Lung; Microscopy, Electron; Platelet Aggregation; Pulmonary Embolism; Rats; Triolein

Topics: Animals; Centrifugation; Chromatography, Thin Layer; Disease Models, Animal; Dogs; Embolism, Fat; Fatty Acids, Nonesterified; Glycerides; Iodine Radioisotopes; Lung; Male; Perfusion; Phospholipids; Pulmonary Embolism; Sterols; Triglycerides; Triolein

Topics: Animals; Blood Volume; Embolism, Fat; Fibula; Fractures, Bone; Hematoma; Histamine; Injections, Intramuscular; Injections, Subcutaneous; Iodine Isotopes; Lipid Metabolism; Pulmonary Embolism; Rabbits; Tibial Fractures; Triolein

Topics: Animals; Biopsy; Blood Coagulation Tests; Bone and Bones; Collagen; Disease Models, Animal; Disseminated Intravascular Coagulation; Dogs; Embolism, Fat; Exudates and Transudates; Fibrin; Fractures, Bone; Hindlimb; Hypoxia; Leukocytes; Lung; Microscopy; Microscopy, Electron; Muscles; Musculoskeletal System; Pulmonary Edema; Pulmonary Embolism; Triolein

Topics: Animals; Autoradiography; Bandages; Bone Marrow; Embolism, Fat; Hematoma; Iodine Isotopes; Kidney; Lung; Oils; Pressure; Pulmonary Embolism; Rabbits; Thyroid Gland; Tibial Fractures; Triolein

Topics: Animals; Blood Coagulation; Disease Models, Animal; Disseminated Intravascular Coagulation; Embolism, Fat; Female; Male; Pulmonary Embolism; Rabbits; Triolein

Fat labeled with triolein-(131)I was introduced through a burr hole into single tibial marrow cavities and the hole was sealed. The radioactivity over the thorax was monitored for 2-5 hours. After sacrifice, the radioactivity was determined in lungs, injected tibia or leg, kidneys, brain, thyroid gland and blood. Presence of pulmonary embolic fat was verified by histologic methods. Intravasation occurred after closure of the burr hole; it was delayed in several animals and failed to occur in 1 animal. The following mean percentages of the injected activity were found: in lungs 44.8% (0.04-85.1%); in tibia 44.7% (7.1-96.8%); in other investigated tissues and organs collectively, less than 1%. In another group, the tibia was fractured either immediately after injection of the labeled fat and closure of the burr hole, or while intravasation was in progress. After 2-5 hours, the lungs contained 23.2% (0.1-65.6) of the labeled fat, which was significantly less than in animals without fracture. In 2 animals, the needle was sealed into the burr hole, and the pressure necessary to produce intravasation was measued. A pressure of 50-100 mm of H(2)O produced pulmonary fat embolism as rapidly as the fat was injected.

Topics: Animals; Blood Vessels; Bone and Bones; Bone Marrow; Embolism, Fat; Female; Injections, Intravenous; Iodine Isotopes; Lipid Metabolism; Lipids; Lung; Male; Pressure; Pulmonary Embolism; Rabbits; Radionuclide Imaging; Tibia; Time Factors; Triolein

Topics: Animals; Brain; Brain Stem; Carotid Arteries; Cheyne-Stokes Respiration; Choroid Plexus; Embolism, Fat; Eye; Hypertension; Injections, Intra-Arterial; Intracranial Embolism and Thrombosis; Iodine Isotopes; Ischemic Attack, Transient; Lung; Mesencephalon; Pons; Pulmonary Embolism; Rabbits; Spasm; Triolein; Vascular Diseases

Topics: Adult; Animals; Austria; Biopsy; Blood Volume; Embolism, Fat; Femoral Fractures; Fractures, Bone; Humans; Lung; Male; Pulse; Rabbits; Shock, Traumatic; Triolein

Topics: Animals; Blood Pressure; Capillaries; Carotid Arteries; Dogs; Embolism, Fat; Extracorporeal Circulation; Female; Injections, Intra-Arterial; Iodine Isotopes; Lung; Lung Transplantation; Male; Pulmonary Circulation; Transplantation, Homologous; Triolein

Topics: Animals; Autopsy; Dogs; Embolism, Fat; Fatty Acids, Nonesterified; Fractures, Bone; Humans; Hypoxia; Injections, Intravenous; Intracranial Embolism and Thrombosis; Iodine Isotopes; Lethal Dose 50; Lung; Oleic Acids; Oxygen; Pulmonary Embolism; Rabbits; Triolein

Topics: Animals; Brain; Dextrans; Dogs; Embolism, Fat; Heparin; Iodine Isotopes; Kidney; Lipid Metabolism; Lipids; Lung; Radionuclide Imaging; Triolein

Topics: Animals; Embolism, Fat; Hypoxia; Injections, Intra-Arterial; Injections, Intravenous; Intracranial Embolism and Thrombosis; Iodine Isotopes; Lung; Oxygen Inhalation Therapy; Pneumothorax; Pulmonary Embolism; Rabbits; Triolein

Topics: Animals; Brain Chemistry; Embolism, Fat; Hypoxia; Intracranial Embolism and Thrombosis; Iodine Isotopes; Kidney; Liver; Lung; Methods; Oxygen; Pneumothorax; Pulmonary Circulation; Pulmonary Embolism; Rabbits; Radioisotopes; Respiration; Rubidium; Triolein

Topics: Animals; Blood Cell Count; Blood Platelets; Carbon Dioxide; Dogs; Embolism, Fat; Injections, Intravenous; Lung; Lung Compliance; Models, Biological; Oleic Acids; Oxygen; Partial Pressure; Surface-Active Agents; Thrombocytopenia; Triolein

Topics: Animals; Embolism, Fat; Hypotension; Injections, Intravenous; Iodine Isotopes; Lung; Male; Pulmonary Artery; Rabbits; Radionuclide Imaging; Shock, Hemorrhagic; Triolein

Topics: Animals; Cortisone; Embolism, Fat; Hydrocortisone; Injections, Intramuscular; Injections, Intravenous; Male; Oleic Acids; Pulmonary Embolism; Rats; Triolein

Topics: Animals; Brain Chemistry; Embolism, Fat; Fatty Acids, Nonesterified; Female; Hypoxia; Iodine Isotopes; Lipase; Liver; Lung; Male; Rabbits; Respiration; Triolein

Topics: Animals; Embolism, Fat; Lipase; Lung; Male; Myocardium; Rats; Triolein

Topics: Animals; Aprotinin; Bradykinin; Cats; Embolism, Fat; Rabbits; Shock, Hemorrhagic; Triolein

Topics: Brain; Embolism, Fat; Injections, Intravenous; Iodine Isotopes; Kidney; Lipid Metabolism; Liver; Lung; Muscles; Myocardium; Organ Specificity; Pulmonary Embolism; Radioisotopes; Radionuclide Imaging; Rats; Research; Thyroid Gland; Triolein

Topics: Cats; Embolism; Embolism, Fat; Lecithins; Mineral Oil; Oleic Acid; Oleic Acids; Phosphatidylcholines; Pulmonary Embolism; Research; Starch; Surface Tension; Surface-Active Agents; Triolein

Topics: Absorption; Animals; Blood Chemical Analysis; Dogs; Embolism; Embolism, Fat; Fats; Humans; Iodine Isotopes; Lipid Metabolism; Lymph; Research; Triolein; Wounds and Injuries

Topics: Animals; Blood; Dogs; Embolism; Embolism, Fat; Femoral Fractures; Iodine Isotopes; Lipid Metabolism; Lymphatic System; Research; Triolein