Surfactant Attenuates Air Embolism-Induced Lung Injury by Suppressing NKCC1 Expression and NF-κB Activation.

Excessive amounts of air can enter the lungs and cause air embolism (AE)-induced acute lung injury (ALI). Pulmonary AE can occur during diving, aviation, and iatrogenic invasive procedures. AE-induced lung injury presents with severe hypoxia, pulmonary hypertension, microvascular hyper-permeability, and severe inflammatory responses. Pulmonary AE-induced ALI is a serious complication resulting in significant morbidity and mortality. Surfactant is abundant in the lungs and its function is to lower surface tension. Earlier studies have explored the beneficial effects of surfactant in ALI; however, none have investigated the role of surfactant in pulmonary AE-induced ALI. Therefore, we conducted this study to determine the effects of surfactant in pulmonary AE-induced ALI. Isolated-perfused rat lungs were used as a model of pulmonary AE. The animals were divided into four groups (n = 6 per group): sham, air embolism (AE), AE + surfactant (0.5 mg/kg), and AE+ surfactant (1 mg/kg). Surfactant pretreatment was administered before the induction of pulmonary AE. Pulmonary AE was induced by the infusion of 0.7 cc air through a pulmonary artery catheter. After induction of air, pulmonary AE was presented with pulmonary edema, pulmonary microvascular hyper-permeability, and lung inflammation with neutrophilic sequestration. Activation of NF-κB was observed, along with increased expression of pro-inflammatory cytokines, and Na-K-Cl cotransporter isoform 1 (NKCC1). Surfactant suppressed the activation of NF-κB and decreased the expression of pro-inflammatory cytokines and NKCC1, thereby attenuating AE-induced lung injury. Therefore, AE-induced ALI presented with pulmonary edema, microvascular hyper-permeability, and lung inflammation. Surfactant suppressed the expressions of NF-κB, pro-inflammatory cytokines, and NKCC1, thereby attenuating AE-induced lung injury.

Iatrogenic cerebral arterial gas embolism from flushing of the arterial line in two calves.

BACKGROUND: Measurement of invasive blood pressure as reflection of blood flow and tissue perfusion is often carried out in animals during general anesthesia. Intravascular cannulation offers the potential for gas to directly enter the circulation and lead to arterial gas embolism. Cerebral arterial gas embolism may cause a spectrum of adverse effects ranging from very mild symptoms to severe neurological injury and death. Although several experimental models of arterial gas embolism have been published, there are no known published reports of accidental iatrogenic cerebral arterial gas embolism from flushing of an arterial line in animals. CASE PRESENTATION: A 7-day-old Red Holstein-Friesian calf (No. 1) and a 28-day-old Holstein-Friesian calf (No. 2) underwent hot iron disbudding and sham disbudding, respectively, under sedation and cornual nerve anesthesia. Invasive arterial blood pressure was measured throughout the procedure and at regular intervals during the day. Before disbudding, a sudden and severe increase of blood pressure was observed following flushing of the arterial line. Excitation, hyperextension of the limbs and rapid severe horizontal nystagmus appeared shortly thereafter. Over the following minutes, symptoms ameliorated and blood pressure normalized in both cases. Prompt diagnosis was missed in calf 1; supportive fluid therapy was provided. Severe deterioration of neurologic status occurred in the following 24 h and culminated with stupor. The calf was euthanized for ethical reasons and the histological examination revealed extensive cerebral injury. Treatment of calf 2 consisted of supportive fluid and oxygen therapy; furosemide (1 mg/kg IV) was injected twice. Calf 2 appeared clinically normal after 2 h and showed no neurologic sequelae on a 3-month-follow up period. CONCLUSIONS: There are no known reports of cerebral arterial gas embolism following flushing of the auricular arterial line in calves. The injection of a small amount of air at high pressure in a peripheral artery may lead to a significant cerebral insult. The clinical presentation is non-specific and can favour misdiagnosis and delay of therapy.

A Rare Case of Cerebral Air Embolism Caused by Pulmonary Arteriovenous Malformation After Removal of a Central Venous Catheter.

Cerebral air embolism following central venous catheter (CVC) removal is extremely rare. We report a case of cerebral air embolism with loss of consciousness after removal of CVC caused by pulmonary arteriovenous malformation (PAVM). Computed tomography revealed air bubbles in the internal carotid arteries along the sulci in the cerebral hemispheres, as well as a PAVM. The cerebral air embolism was treated with hyperbaric oxygen and intravenous thrombolytic therapy, and transcatheter embolization of the PAVM was performed. When inserting/removing CVC in a patient with a small PAVM, treatment of the PAVM, irrespective of its size, could prevent the type of complication that occurred in our present case.

Case of pneumatosis intestinalis and hepatic portal venous gas following a laparoscopic right hemicolectomy.

Hepatic portal venous gas (HPVG) in most cases signifies either mechanical migration of air into the portal system due to bowel ischaemia (pneumatosis intestinalis) or portal sepsis due to gas-forming organisms. Successful management of portal sepsis involves early identification of the condition, intensive resuscitation, broad-spectrum antibiotics and a laparotomy for possible bowel ischaemia. In this report, we discuss the case of a patient with pneumatosis intestinalis and HPVG after an elective laparoscopic right hemicolectomy. After an initial slow recovery, on postoperative day seven, the patient had profuse diarrhoea and confusion, and was hyponatraemic. A CT scan revealed pneumatosis intestinalis and HPVG. A laparotomy showed no obvious cause for HPVG and there was no ischaemic bowel. She was managed with intensive care, hyperbaric oxygen therapy, broad-spectrum antibiotics and total-parenteral nutrition. She has made a good recovery. This case highlights the presenting features, differential diagnoses, and management of pneumatosis intestinalis and HPVG.

Effects of perfluorocarbon emulsions on microvascular blood flow and oxygen transport in a model of severe arterial gas embolism.

BACKGROUND: Arterial gas embolism (AGE) is a clinical problem that occurs directly in cardiopulmonary bypass machines in open-heart surgeries, or indirectly (through cardiac or pulmonary right to left shunts) in dive accidents, resulting in serious morbidity and even death. Perfluorocarbon (PFC) emulsions have been used for the treatment of AGE in an animal model. We hypothesized that PFC emulsions enhance microvascular blood flow, speed bubble resolution, and oxygenation in AGE compared with saline in a model of cremaster muscle from anesthetized rats. MATERIALS AND METHODS: AGE was induced by direct air injection into the femoral artery ipsilateral to the studied cremaster muscle. Microhemodynamics, microvascular, and tissue oxygenation were determined before and after treatment with two different commercial PFC emulsions (C10F20, Oxycyte; Oxygen Biotherapeutics, Inc and C10F18, PHER-O2; Sanguine Corporation, Inc) compared with saline in real time using brightfield and phosphorescence microscopy. RESULTS: Blood pressure and heart rate remained unchanged. Systemic PO2, oxygen (O2) content, and glucose were higher in PFC groups, whereas hematocrit dropped in all groups. Arteriolar blood flow went up 85% and 80% of baseline after C10F20 and C10F18 treatments, respectively, versus 11% after saline treatment. Arteriolar and tissue PO2, and O2 delivery were higher in PFC groups compared with the control group. There was an increase in arteriolar blood flow, reduction in diffusional resistance of O2 in the plasma, and improved tissue oxygenation. CONCLUSIONS: Administration of PFC emulsions in AGE is superior to saline primarily because of surfactant properties along with air bubble reabsorption.

Pefluorocarbon inhibition of bubble induced Ca2+ transients in an in vitro model of vascular gas embolism.

Endothelial injury resulting from deleterious interaction of gas microbubbles occurs in many surgical procedures and other medical interventions. The symptoms of vascular air embolism (VAE), while serious, are often difficult to detect, and there are essentially no pharmaceutical preventative or post-event treatments currently available. Perfluorocarbons (PFCs), however, have shown particular promise as a therapeutic option in reducing endothelial injury both in- and ex-vivo. Recently, we demonstrated the effectiveness of Oxycyte, a third-generation PFC formulated in a phosphotidylcholine emulsion, using an in vitro model of VAE developed in our laboratory. This apparatus allows live cell imaging concurrent with precise manipulation of physiologically sized microbubbles so that they may be brought into individual contact with human umbilical vein endothelial cells dye-loaded with the Ca(2+) sensitive Fluo-4. Herein, we expand use of this fluorescence microscopy-based cell culture model. Specifically, we examined the concentration dependence of Oxycyte in reducing both the amplitude and frequency of large intracellular Ca(2+) currents that are both a hallmark of bubble contact and a quantifiable indication that abnormal intracellular signaling has been triggered. We measured dose dependence curves and fit the resultant data using a modified Black and Leff operational model of agonism. The half maximal inhibitory concentrations of Oxycyte for (i) inhibition of occurrence and (ii) amplitude reduction were 229 ± 49 µM and 226 ± 167 µM, respectively. This investigation shows the preferential gas/liquid interface occupancy of the PFC component of Oxycyte over that of mechanosensing glycocalyx components and validates Oxycyte's specific surfactant mechanism of action. Further, no lethality was observed for any concentration of this bioinert PFC, as it acts as a competitive allosteric inhibitor of syndecan activation to ameliorate cell response to bubble contact.

Surfactant reduction of cerebral infarct size and behavioral deficit in a rat model of cerebrovascular arterial gas embolism.

Gas embolism occurs commonly in cardiac and vascular surgery and decompression sickness. The goals of this study were to develop a new in vivo rat model of cerebrovascular arterial gas embolism and to determine the effects of exogenous surfactants on resultant brain infarct volume and accompanying long-term neurological dysfunction using the model. Unilateral cerebral arterial gas embolism was induced in Sprague Dawley rats, including groups receiving intravenous Pluronic F-127 (PF-127) and Oxycyte perflourocarbon surfactant pretreatment. Magnetic resonance imaging (MRI) was performed at 24 and 72 h postembolism to determine infarct volume. The elevated body swing test (EBST), limb-placement test, proprioception forelimb and hindlimb tests, whisker tactile test, and Morris Water Maze test were performed to assess motor behavior, somatosensory deficit, and spatial cognitive function out to 29 days after embolization. A stable stroke model was developed with MRI examination revealing infarction in the ipsilateral cerebral hemisphere. Gas embolized rats had significant cognitive and sensorimotor dysfunction, including approximately threefold increase in Morris Water Maze latency time, ∼20% left-sided biasing in EBST performance, 0.5 to 1.5 (mean) point score elevations in the proprioception and whisker tactile tests, and 3.0 point (mean) elevation in the limb-placement test, all of which were persistent throughout the postembolic period. Surfactant prophylaxis with either PF-127 or Oxycyte rendered stroke undetectable by MRI scanning and markedly reduced the postembolic deficits in both cognitive and sensorimotor performance in treated rats, with normalization of EBST and whisker tactile tests within 7 days.

Delayed cerebral air embolism complicating percutaneous needle biopsy of the lung.

Computed tomography-guided percutaneous needle biopsy of the lung is a common and frequently performed procedure for diagnosis of lung lesions. However, this procedure is not without risks. The major complications include pneumothorax and hemoptysis, which are mild and self-limiting. The rare complications include air embolism, tension pneumothorax, pulmonary hemorrhage, and tumor dissemination, which are severe and life threatening. Cerebral air embolism is a very rare and fatal complication. In previous reports, cerebral air embolism generally occurred during or immediately after lung biopsy. Herein, we present the first case of cerebral infarction secondary to cerebral air embolism 6 hours after computed tomography-guided lung biopsy.

Protective effects of fluoxetine on decompression sickness in mice.

Massive bubble formation after diving can lead to decompression sickness (DCS) that can result in central nervous system disorders or even death. Bubbles alter the vascular endothelium and activate blood cells and inflammatory pathways, leading to a systemic pathophysiological process that promotes ischemic damage. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory properties at the systemic level, as well as in the setting of cerebral ischemia. We report a beneficial clinical effect associated with fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90 msw for 45 min before rapid decompression. The experimental group received 50 mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46) while controls were not treated (n = 45). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine IL-6 detection. There were significantly fewer manifestations of DCS in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p = 0.004). Survivors showed a better and significant neurological recovery with fluoxetine. Platelets and red cells were significantly decreased after decompression in controls but not in the treated mice. Fluoxetine reduced circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded that fluoxetine decreased the incidence of DCS and improved motor recovery, by limiting inflammation processes.

Surfactant properties differentially influence intravascular gas embolism mechanics.

Gas bubble motion in a blood vessel causes temporal and spatial gradients of shear stress at the cell surface lining the vessel wall as the bubble approaches the cell, moves over it and passes it by. Rapid reversals occur in the sign of the shear stress imparted to the cell surface during this motion. These may result in injury to the cell. The presence of a soluble surfactant in the bulk medium reduces the level of the shear stress gradients imparted to the cell surface as compared to an equivalent surfactant-free system and is an important therapeutic aid. This is particularly true for a very small vessel. In this study, we analyze various physical and chemical properties of any given soluble surfactant to ascertain the relative significance of the property of the surfactant on the reduction in the level of the shear stress gradients imparted to the cell surface in such a vessel. While adsorption, desorption, and maximum possible monolayer interface surfactant concentration significantly impact the shear stress levels, physical properties such as the bulk or surface diffusivity do not appear to have large effects. At a given diameter, surfactants with k(a)/(k(d)d>O(10)⁻5 and Γ(∞)/C(0)d>9.5 x 10⁻4 are noted to be preferable from the point of view of an increased gap size between the bubble and vessel wall, and a corresponding reduction in the shear stress level imparted to an endothelial cell. The shear stress characteristics of nearly occluding bubbles, in contrast with smaller sized bubbles under identical conditions, are most affected by the introduction of a surfactant in regard to shear stress levels. These observations could form a basis for choosing surfactants in treating gas embolism related illnesses.

Hydrogen peroxide ingestion associated with portal venous gas and treatment with hyperbaric oxygen: a case series and review of the literature.

INTRODUCTION: Ingestion of concentrated hydrogen peroxide (H(2)O(2)) has been associated with venous and arterial gas embolic events, hemorrhagic gastritis, gastrointestinal bleeding, shock, and death. Although H(2)O(2) is generally considered a benign ingestion in low concentrations, case reports have described serious toxicity following high concentration exposures. Hyperbaric oxygen (HBO) has been used with success in managing patients suffering from gas embolism with and without manifestations of ischemia. METHODS: Poison center records were searched from July 1999 to January 2010 for patients with H(2)O(2) exposure and HBO treatment. Cases were reviewed for the concentration of H(2)O(2), symptoms, CT scan findings of portal gas embolism, HBO treatment, and outcome. RESULTS; Eleven cases of portal gas embolism were found. Ages ranged from 4 to 89 years. All but one ingestion was accidental in nature. In 10 cases 35% H(2)O(2) was ingested and in 1 case 12% H(2)O(2) was ingested. All abdominal CT scans demonstrated portal venous gas embolism in all cases. Hyperbaric treatment was successful in completely resolving all portal venous gas bubbles in nine patients (80%) and nearly resolving them in two others. Ten patients were able to be discharged home within 1 day, and one patient had a 3.5-day length of stay. CONCLUSIONS: HBO was successful in resolving portal venous gas embolism from accidental concentrated H(2)O(2) ingestions.

Successful conservative treatment of pneumatosis intestinalis and portomesenteric venous gas in a patient with septic shock.

Pneumatosis intestinalis (PI) and portomesenteric venous gas (PMVG) are alarming radiological findings that signify bowel ischemia. The management of PI and PMVG remain a challenging task because clinicians must balance the potential morbidity associated with unnecessary surgery with inevitable mortality if the necrotic bowel is not resected. The combination of PI, portal venous gas, and acidosis typically indicates bowel ischemia and, inevitably, necrosis. We report a patient with PI and PMVG caused by septic shock who completely recovered after conservative treatment.

Pneumomediastinum, stomach wall and hepatic portal vein gas secondary to partial necrosis of the stomach wall.

The combination of pneumomediastinum, gastric wall gas and hepatic portal vein gas is a challenging clinical problem. Although different causes of the individual gas sign have been reported in the literature, the cause of a triad of these signs in a single patient is less clear, and represents an extremely rare condition. A 65-year-old man presented with severe lower chest and epigastric pain of a few hours' duration. Initial assessment confirmed epigastric tenderness. Computed tomography showed pneumomediastinum, air in the stomach wall, hepatic portal vein gas and bowel dilatation. Small bowel and right colon dilatation was confirmed at laparotomy. The patient was treated subsequently with antibiotics to cover Gram-positive and Gram-negative bacteria, and anaerobes. The patient was discharged in good general condition on the 12th postoperative day. In conclusion, the triad of pneumomediastinum, gastric wall gas and hepatic portal vein gas is an extremely rare condition and associated with gastric necrosis.

A brief review of innovative uses for local anesthetics.

PURPOSE OF REVIEW: Local anesthetics are drugs which have many potentially beneficial actions, especially when used as a continuous intravenous infusion. The following review gives an update on the most recent literature along with some interesting and promising areas where systemic local anesthetics are being implemented. RECENT FINDINGS: Surprisingly little research has been conducted with the use of systemic local anesthetics when considering their cost effectiveness, good side effect profile when used in low-dose infusions, and promising results in the available literature. The in-vivo studies, ranging from case reports to randomized controlled trials, have small sample sizes, yet most have found that low-dose systemic infusions are efficacious for various conditions. SUMMARY: Local anesthetics have many beneficial properties, and promising results have been seen when low-dose infusions are implemented. This review briefly describes the anti-inflammatory properties of local anesthetics and discusses the benefits seen when used systemically for neuroprotection, postoperative ileus, decompression sickness, and glaucoma.

Hepatic portal venous gas complicating septic thrombophlebitis of the superior mesenteric vein.

Hepatic portal venous gas is a rare radiological finding with a wide spectrum of underlying pathologies. We describe a case of hepatic portal venous gas due to septic thrombophlebitis of the superior mesenteric vein. The clinical management of portomesenteric venous gas and the importance of computed tomography in delineating its underlying causes are discussed.

Reduction in air bubble size using perfluorocarbons during cardiopulmonary bypass in the rat.

BACKGROUND: Perfluorocarbon (PFC) emulsions are artificial oxygen-carrying compounds with a high solubility for gases that have experimentally been shown to ameliorate cerebral air embolism. Cerebral air embolism has been associated with adverse cerebral outcomes after cardiac surgery using cardiopulmonary bypass (CPB). We designed this study to test whether PFC emulsions could reduce the volume of bubbles within the CPB circuit. METHODS: Male Sprague-Dawley rats undergoing 60 min of normothermic nonpulsatile CPB were randomized to one of the three groups. The PFC group (n = 10) received 60% O(2)/36% N(2)/4% CO(2) via the membrane oxygenator and 2.7 g/kg (4.5 mL/kg) of PFC into the venous reservoir; the control group (n = 10) received the same gas mixture and 4.5 mL/kg of saline; the N(2)O group (n = 6) was exposed to 36% N(2)O/60% O(2)/4% CO(2) and received 4.5 mL/kg of saline. After 10 min and 35 min of CPB, 400 microL of air was injected into a bubble chamber in the CPB circuit. After 20 min, the bubble was removed for volumetric analysis. RESULTS: Compared with baseline, the bubble decreased 13% +/- 5% in size in the PFC group and increased 46% +/- 9% in the nitrous oxide group, both of these changes significantly different from the control group (P < 0.0001). CONCLUSION: The results suggest that PFC administration may be useful in reducing the volume of gaseous bubbles present during CPB.

A case of non-lethal pulmonary air embolism after leukapheresis catheter removal.

Mononuclear cell leukapheresis requires good-quality venous access. Catheter placement and removal of the catheter may be associated with life-threatening local or systemic complications. Thus, prompt recognition of these complications and appropriate therapy can be life-saving. We report the case of a young man who presented with an air embolism following removal of a jugular venous catheter after peripheral blood stem cell collection. We have reviewed the signs and symptoms presented by the patient and the methodology used to remove the catheter. Catheter removal requires careful attention in order to avoid potentially serious complications.