Intralipid Group Research Articles

Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart

BackgroundInsulin resistance has been independently related to heart failure. However, the specific mechanisms of high FFA levels in the pathophysiology of heart failure in insulin-resistant states are remain largely unclear. This study investigated whether elevated circulating free fatty acids (FFA) levels result in impaired cardiac structure and function in vivo via insulin-related signaling pathways in myocardium.MethodsMale Wistar rats were randomly divided into the intralipid group (20% intralipid plus heparin infusion) and the control group (glycerol infusion). Blood samples were collected before and after 6-, 12-, and 24-h infusions. Cardiac structure and function were measured using echocardiography. Maximum velocity of myocardial contraction (+dP/dt max) and diastole (−dP/dt max) were measured using a physiological polygraph in vivo. Heart tissues were collected for western blotting.ResultsCompared with the control group, plasma FFA, plasma glucose, and serum insulin levels increased significantly in the intralipid group. With increasing infusion time, cardiac function in the intralipid group decreased gradually compared with the control group. After a 24-h infusion, early (E’, cm/s) diastolic peak velocities and (−dP/dt max) decreased significantly. Protein expression of phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt, and phosphorylated Akt in myocardium increased after a 6-h infusion and decreased significantly after a 24-h infusion in the intralipid group. Protein expression of glucose transporter type 4 (GLUT4), Adenosine 5′-monophosphate -activated protein kinase (AMPK), phosphorylated AMPK(p-AMPK), and endothelial nitric oxide synthase (eNOS) in myocardium gradually decreased in the intralipid group.ConclusionsElevated FFA levels may impair cardiac function and cardiac dysfunction might result from myocardial insulin resistance with significant changes to PI3K-Akt-GLUT4 and AMPK-eNOS signaling pathways with increasing FFA levels.

The Protective Effect of Propofol Against Ischemia–Reperfusion Injury in the Interlobar Arteries: Reduction of Abnormal Cx43 Expression as a Possible Mechanism

Background/Aims: This experimental study aims to observe whether the protective effect of propofol against renal ischemia–reperfusion injury (IRI) in the rat interlobar artery occurs through altered expression of the gap junction protein connexin 43 (Cx43). Methods: This study randomly divided male Sprague Dawley (SD) rats into an untreated control group, a sham-operated control group (sham group), an ischemia–reperfusion group (IR group), a propofol group (propofol+IR group) and a fat emulsion group (Intralipid group). The ischemia/reperfusion model was prepared through resection of the right kidney and noninvasive arterial occlusion of the left kidney. Forty-five minutes after renal ischemia–reperfusion, an automatic biochemical analyzer was employed to measure blood urea nitrogen (BUN) and serum creatinine (SCr); changes in renal tissue pathology were observed using hematoxylin and eosin (HE) staining, and the vasomotor activity of the interlobar artery was detected using a pressure mechanogram technique. The protein expression of Cx43 in renal artery cross-sections was determined through western blotting. Results: The experimental study confirmed that the BUN and SCr of rats markedly increased after ischemia–reperfusion injury; additionally, we observed some coagulation necrosis and shedding of cells, some solidification of nuclear chromatin, degeneration of cytoplasmic vacuoles, high renal interstitial vascular congestion and obvious inflammatory cell infiltration, characterized by focal hemorrhages. Furthermore, the contraction activity of the renal interlobar artery greatly decreased, and the tension of the arteries in the renal lobe increased remarkably. After the gap junction blocking agents 2-APB and Gap27 were applied, the systolic velocity of blood vessels and the vascular contraction rate both decreased. In addition, the expression of Cx43 in kidney tissues increased markedly. The damage was more severe after 24 h of ischemic reperfusion than after only 4 h. However, after pretreatment with propofol, regardless of whether ischemia–reperfusion was applied for 4 h or 24 h, the previously increased expression of Cx43 decreased obviously, and all forms of renal damage were reversed. Conclusion: Our research suggests new ways for propofol to relieve ischemia–reperfusion injury by decreasing the abnormal expression of the gap junction protein Cx43. This study reveals a novel mechanism for the action of propofol against IRI, and we hope this finding will lead to new treatments for IRI.

The effect of intralipid infusion as postconditioning agent to reduce the myocardial reperfusion injury in coronary surgery patients

Background Intralipid is a safe fat emulsion for human use, it has been proved that administration of intralipid at the onset of reperfusion protect isolated heart against ischemic/reperfusion and resulted in reduction of infarction size. The current study investigated the efficacy of intralipid as a postconditioning agent to attenuate myocardial injury in patients undergoing coronary artery bypass graft surgery. Patients and methods Fifty patients undergoing coronary artery bypass graft operation were randomly assigned into two groups. Intralipid group (IL group), which received 1.5 ml/kg intralipid 20% after aortic cross clamping removal and the control group (C group), which received normal saline 0.9% in the same volume. The primary outcome of the study is the postischemic myocardial injury assessed by measuring cardiac troponin (CTnI) and cardiac-specific creatine kinase (CK-MB) pre-CPB (cardiopulmonry bypass) than every 6 h till 48 h post-CPB. The secondary outcomes are the haemodynamic effect of intralipid on systemic and pulmonary circulation and clinical effect on inotropic uses and stay in ICU and hospital for all patients. Results Throughout the study there was no significant changes in the mean arterial blood pressure, heart rate, central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, systemic vascular resistance (P>0.05). Cardiac index significantly increased at post-CPB from the pre-CPB in the intralipid group compared to the control group (P Conclusion Intralipid could be a safe pharmacological postconditioning agent for the critical reperfusion time and can reduce the postischemic reperfusion injury indicated by the reduction in postischemic cardiac enzymes CTnI and CK-MB.

A comparison of lipid minimization strategies in children with intestinal failure

PurposeThe purpose of this study was to compare outcomes of lipid minimization with either Intralipid (IL) or Omegaven® in children with intestinal failure (IF) who developed intestinal failure-associated liver disease (IFALD) while receiving parenteral nutrition (PN). MethodsA retrospective review of children with IF requiring PN who developed IFALD (direct bilirubin >2 mg/dL) while receiving IL (2009–2016) was performed. Clinical characteristics, nutritional, and laboratory values were compared between children treated with reduced IL or Omegaven®. Results16 children were reviewed (8 treated with IL and 8 treated with Omegaven® at a median dose of 1g/kg/d). Both groups had similar demographics, small bowel length, and parenteral nutritional intake during the study (82.9±27.1 kcal/kg/d vs. 75.9±16.5 kcal/kg/d, p=0.54). The mean direct bilirubin (DBili) prior to initiating treatment was 7.8±4.3 mg/dL and 7.5±3.5 mg/dL (p=0.87) in the IL and Omegaven® groups, respectively. The IL group took a median of 113 days to achieve a DBili <0.5 mg/dL compared to 124 days in the Omegaven® group (p=0.49). There were no differences in markers of liver function or growth trajectories among groups. ConclusionsLipid minimization with either IL or Omegaven® has similar success in achieving a normal DBili in children with IF and IFALD without major differences in nutritional status or growth. Type of studyTreatment Study Level of evidenceIII.

The effects of propofol on the growth behavior of hepatoma xenografts in Balb/c mice

ObjectiveStudies on the effects of propofol on the growth of hepatoma xenografts in Balb/c mice. MethodsIn an effort to establish a hepatoma-xenograft model of BALB/C mice, human hepatocellular carcinoma cells SMMC-7721 were inoculated subcutaneously into BALB/C mice. Forty mice were randomly divided into five different groups (n=8): control group (C group), Intralipid group (Y group), low dose (50mg/kg) propofol group (P1 group), medium dose (100mg/kg) propofol group (P2 group) and high dose (150mg/kg) propofol group (P3 group). The tumor volume was measured before treatment and every 3days after treatment (T0d-T18d, T0 represents time point before treatment, T3d-T18d represent time points every 3days after treatment for a total of 18 days). All mice were sacrificed 19days after drug withdrawal. The tumor masses were extracted, weighed, and the tumor inhibition rate of propofol was calculated. The protein levels of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in the xenografted tumors were analyzed by immunohistochemistry staining. ResultsNo statistical significance in the tumor volume at T0d (before treatment), T3d (3days after treatment), and T6d (6days after treatment) among the five groups (P>0.05) could be determined. Compared to group C, the tumor volumes in the P1, P2, and P3 groups were found to be significantly decreased in size upon increasing the propofol dosages (P<0.05). There was no statistical significance at time points T9d-T18d in group Y compared to group C (P>0.05). The tumor weights in the P1, P2, and P3 groups were found to be significantly lower as the propofol dosages increased (P<0.05), with no statistical significance determined in group Y (P>0.05). MMP-2 and VEGF protein levels were found to be significantly lower in the P1, P2, and P3 groups as the propofol dosages increased (P<0.05), with no statistical significance in group Y (P>0.05). ConclusionWithin a certain range, propofol was found to inhibit tumor growth and expression of MMP-2 and VEGF proteins in hepatoma xenografts in BALB/C mice in a dose-dependent manner.

Intralipid Vehicle Does Not Interfere with the Efficacy of Progesterone in Attenuating Edema following Traumatic Brain Injury.

The recent disappointing results of phase III trials for progesterone (PROG) in traumatic brain injury (TBI) have triggered speculation about reasons for the negative outcomes. One confounding factor may have been the vehicle used to administer PROG. Virtually all of the many pre-clinical experiments informing the clinical trials and reporting beneficial PROG effects used more soluble 2-hydroxypropyl-b-cyclodextrin as a vehicle given intraperitoneally or subcutaneously rather than a lipid formulation given intravenously (IV). The present investigation compared the effect of PROG infusion with that of lipid emulsion (Intralipid®) as a carrier/vehicle on edema following TBI in rats. Eight-mg/kg doses of PROG with 20% Intralipid were given IV via central venous catheter beginning 1 h post-injury over a 1 h duration (1.2 mL/h). Animals were killed and brains removed at 24 h post-injury. All the brain-injured groups showed more edema compared with the control group. However, PROG+Intralipid significantly attenuated cerebral swelling compared with Intralipid alone. No difference was observed between the TBI-alone and Intralipid groups. Although this study used much a smaller volume and shorter duration of Intralipid infusion than the clinical trials (up to 5 days of continuous infusion), our results suggest that the use of Intralipid in rats did not prevent or mask the beneficial effect of PROG.

Effect of emulsified isoflurane post-conditioning on mitochondrial function during lung ischemia-reperfusion in rats: an in vitro experiment

Objective To evaluate the effect of emulsified isoflurane post-conditioning on the mitochondrial function during lung ischemia-reperfusion (I/R) in rats in an in vitro experiment. Methods Twenty-four SPF healthy male Sprague-Dawley rats, weighing 250-300 g, were used in the study.After the animals were anesthetized, the lungs were removed, connected to the perfusion system and then divided into 4 groups (n=6 each) using a random number table: control group (group C), group I/R, emulsified isoflurane post-conditioning group (group EI) and intralipid post-conditioning group (group IL). After 20 min of equilibration, the lungs were continuously perfused for 105 min in group C, and the lungs were subjected to 45 min ischemia followed by 60 min reperfusion to establish the model of lung I/R injury in the other three groups.During the reperfusion period, the common perfusate was used in group I/R, the perfusate containing 1.68 mmol/L emulsified isoflurane was used in group EI, and the equal volume of perfusate containing 30% intralipid was used in group IL.At the end of the equilibration (T0), immediately after beginning of reperfusion (T1) and at 30 and 60 min of reperfusion (T2, 3), the arterial oxygen partial pressure (PaO2), airway resistance, pulmonary compliance and tidal volume (VT) were recorded.The right upper lobe of the lung was removed at T3 for determination of wet to dry weight ratio (W/D ratio). The right middle lobe of the lung was removed at T3 for pathologic examination with light microscope.The contents of reactive oxygen species (ROS), NAD+ and ATP in lung tissues were detected. Results Compared with group C, the PaO2, pulmonary compliance and VT were significantly decreased, and the airway resistance was increased at T1-3, and the W/D ratio and ROS content were increased, and NAD+ and ATP contents were decreased at T3 in I/R, EI and IL groups (P<0.05). Compared with I/R and IL groups, the PaO2, pulmonary compliance and VT were significantly increased, and the airway resistance was decreased at T2, 3, and the W/D ratio and ROS content were decreased, and NAD+ and ATP contents were increased at T3 in group EI (P<0.05). The pathologic changes of lungs were significantly attenuated in group EI as compared with group I/R. Conclusion The mechanism by which emulsified isoflurane post-conditioning attenuates lung I/R injury is related to decrease in mitochondrial dysfunction in rats in an in vitro experiment. Key words: Isoflurane; Fat emulsions, intravenous; Reperfusion injury; Lung; Mitochondrial; Ischemia post-conditioning

Effect of prolonged propofol infusion on myocardial enzyme, mitochondrial cytochrome C and adenosine triphosphate in rabbits

To explore the effect of long-time propofol infusion on myocardial enzymes, mitochondrial cytochrome C and ATP in rabbits. Methods: A total of 18 New Zealand rabbits were randomly divided into 3 groups: a control group, a propofol group and an intralipid group. The rabbits were continuously infused with 0.9% normal saline in the control group, 1% propofol in the propofol group, and 10% intralipid in the intralipid group, respectivey. The arterial blood was collected at 0, 8, 16 h and the end of experiment to examine creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the end, the myocardial mitochondria from myocardial tissues was separated by differential centrifugation, and mitochondrial cytochrome C content and adenosine triphosphate (ATP) levels were examined by high performance liquid chromatography. Results: Compared with the control group, the release of cytochrome C from mitochondria were increased in the propofol group and the intralipid group (both P<0.05), but there was no significant difference between them (P>0.05). There was also no significant difference in the ATP content of the mitochondria among the 3 groups (P>0.05). The levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group compared with that before the infusion (all P<0.05); compared with the control group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group and the intralipid group (all P<0.05); compared with the intralipid group, the levels of CK were increased at 8, 16 and 24 h after infusion in the propofol group (all P>0.05); compared with the control group, the levels of CK-MB were obviously increased in the infusion of propofol for 24 h in the propofol group (P<0.05). Conclusion: The levels of serum CK increase after the infusion of propofol and intralipid for a long time, and the levels of CK-MB also elevate in the infusion of propofol. Propofol and intralipid can increase the release of myocardial mitochondrial cytochrome C, but they don't affect the ATP production in myocardial mitochondrial.

Intralipid supplementation in women with recurrent spontaneous abortion and elevated levels of natural killer cells

ObjectiveTo investigate the efficacy of intralipid supplementation in women with recurrent spontaneous abortion (RSA) and elevated natural killer cell activity undergoing in vitro fertilization/intracytoplasmic sperm injection. MethodsBetween February 10, 2013, and April 30, 2015, a double-blind randomized controlled study was conducted at a center in Egypt. Women with unexplained secondary infertility, RSA, and elevated levels of natural killer cells (>12%) were enrolled and randomly assigned to receive intralipid (2mL diluted at 20% in 250mL saline) or saline (250mL) infusion on the day of oocyte retrieval using random numbers and sealed envelopes. Patients and attending physicians were masked to group assignment. The infusions were repeated within 1week of a positive pregnancy test and then every 2weeks until the end of the first trimester. The primary outcome was chemical pregnancy 14days after embryo transfer. Analyses were by intention-to-treat. ResultsOverall, 296 women were enrolled. Chemical pregnancy was recorded for 84 (58.3%) of 144 women in the intralipid group and 76 (50.0%) of 152 in the control group (P=0.129). ConclusionIntralipid supplementation did not increase frequency of chemical pregnancy. However, findings related to ongoing pregnancy and live birth should be investigated further.ClinicalTrials.gov:NCT01788540

Effects of propofol on lung injury secondary to traumatic brain injury in rats

Objective To evaluate the effect of propofol (PPF) on stress response and lung injury in rats with traumatic brain injury (TBI). Methods A total of 36 SD rats were randomly(random number) divided into sham group, intralipid group, TBI group, PPF1 h group, PPF 2 h group, PPF 6 h group (n=6 in each group). Fluid percussion brain injury models were used. By intraperitoneal injection, intralipid was administered in intralipid group after sham operations, while propofol 100 mg·kg-1 was given to rats in PPF1 h group, PPF 2 h group and PPF 6 h group 1, 2, 6 hours following injury, respectively. Nerve motor function were scored at different intervals, serum concentrations of adrenocorticotropic hormone (ACTH), cortisol (COR) and norepinephrine (NE) were measured 12 h after injury. Seventy-two hours later, all rats were sacrificed and brains were harvested for TTC staining, and lungs taken were stained with HE staining for observation under light microscope and electron microscopy. Results Compared with sham and intralipid group, nerve motor function scores were significantly decreased, and serum concentrations of ACTH, COR and NE were increased significantly in rats after injury. Compared with TBI group, the above biomarkers were improved significantly after propofol injection. There were no significant differences in above biomarkers between PPF 1 h and PPF 2 h group (t= -0.816, t= -0.208, t=0.582, P>0.05) . The differences in COR and NE concentrations between PPF 2 h and PPF 6 h group were statistically significant (t=3.018, P=0.013; t=3.662, P=0.004). Light microscopy demonstrated abundant inflammatory cell infiltration and massive thickening of the alveolar walls, Electron microscopy showed TypeⅡlung epithelial cell swelling, vacuolar degeneration, osmiophilic lamellar corpuscle emptying in cytoplasm, microvilli protrusions decreases in some cytoplasm in TBI group, and pathological damage was improved significantly in PPF 2 h group. Conclusions Propofol may inhibit stress and protect the lung tissue from damage in TBI rats. Key words: Traumatic brain injury; Propofol; Stress; Lung injury; Adrenocorticotropic hormone; Cortisol; Norepinephrine; Pathology

Abstract 253: Complete Reversal of Xylazine-induced Bradycardia With Intralipid in Female Mice

Sudden cardiac arrest accounts for 300 000 to 400 000 deaths annually in united states both in men and women. Cardiac arrest could be due to abnormally slow heart rate known as bradycardia. Bradycardia is a catastrophic event which is associated with significant mortality and morbidity. We have previously shown that Intralipid, an emulsion of soy bean oil, egg yolk phospholipids and glycerol, protects the heart against ischemia/reperfusion injury as well as Bupivacaine induced cardiotoxicity. Here we examined whether intralipid can protects the heart against bradycardia. Wild type female mice C57/Bl6 (2-4 month old) were anesthetized by isoflurane after heparinization. The heart was removed immediately and placed in cold Krebs-Henseleit buffer. The aorta was cannulated and the isolated heart (Langendorff) was perfused with Krebs-Henseleit at 37°C for 15 min for stabilization. Xylazine (100-300 mg) was directly applied to the heart surface for 1-2 min until bradycardia was achieved. The heart was then perfused with either Krebs-Henseleit (KH) solution (control group), or 1% ILP (intralipid group). Hemodynamic parameters and heart rates were recorded with a catheter directly inserted into left ventricle (n=5-8 per group). The heart rates at the baseline before inducing bradycardia was 224±7 beats/min and the left ventricular pressures was 64±4 mmHg. Administration of Xylazine decreased the heart rate significantly to 81±9 beats/min and left ventricular pressure to 5±2 mmHg (p&lt;0.001). Perfusion of the heart with intralipid rapidly restored the heart rate to 209±30 and left ventricular pressure to 59±4 which were not significantly different than their values before inducing bradycardia at the baseline. In the hearts that received Krebs-Henseleit after bradycardia, the heart rate (81±10 beats/min) and left ventricular pressure (20±8 mmHg) were significantly lower than intralipid group. In conclusion Intralipid has the ability to rapidly reverse bradycardia in female mice.

Abstract 442: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis via Mir122 Induction

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.

Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester (CAPE) on Hepatotoxicity and Pancreatic Injury Caused by Dichlorvos in Rats.

The present study was aimed to the investigate the protective effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity and pancreatic injury caused by acute dichlorvos (D) intoxication in rats. Forty-eight Wistar rats were randomly divided into seven groups each containing seven rats except control groups. The groups included control, D, CAPE, IL, D+CAPE, D+IL, and D+CAPE+IL. Total antioxidant status and total oxidative stress levels were measured by automated colorimetric assay. Tissues were evaluated using hematoxylin and eosin (H&E) staining. Tissues were analyzed with hematoxylin and eosin by using standard protocols. Also, Bcl-2, Bax and caspase-3 were evaluated by immunohistochemical method in liver tissue. Total oxidant status in control, CAPE, and IL groups were significantly lower, and total antioxidant status in the D+CAPE, D+IL, and D+IL+CAPE groups were significantly higher compared to the D group. CAPE and IL treatment decreased the apoptotic and mitotic cell count in liver tissue. Parenchymal necrosis caused by dichlorvos is observed in pancreas tissues of rats. Mild congestion and edema formation occurred in pancreas tissues following D+CAPE and D+IL therapies. These results indicate that CAPE and IL have the potential to decrease oxidative stress and hepatic and pancreatic injuries caused by acute dichlorvos intoxication. These drugs can be considered as a new method for supportive and protective therapy against pesticide intoxication.

Adding Emulsified Isoflurane to Cardioplegia Solution Produces Cardiac Protection in a Dog Cardiopulmonary Bypass Model.

This study investigated whether caridoplegia solution with Emulsified Isoflurane (EI) could improve cardiaoprotection in a dog CPB model of great similarity to clinical settings. Adult dogs were randomly assigned to receive one of the following cardioplegia solutions: St. Thomas with EI (group ST+EI), St. Thomas with 30% Intralipid (group ST+EL) and St. Thomas alone (group ST). The aorta was cross-clamped for two hours followed by reperfusion for another two hours, during which cardiac output was measured and dosages of positive inotropic agent to maintain normal hemodynamics were recorded. Serum level of cardiac troponin I (cTnI) and CK-MB were measured. Deletion of cardiac mitochondrial DNA was examined at the end of reperfusion. Compared with ST, ST+EI decreased the requirement of dopamine support while animals receiving ST+EI had a significantly larger cardiac output. ST+EI reduced post-CPB release of cTnI and CK-MB. Mitochondrial DNA loss was observed in only one of the tested animals from group ST+EI while it was seen in all the tested animals from group ST+EL and ST. Addition of emulsified isoflurane into cardioplegia solution protects against myocardial ischemia reperfusion injury. This protective effect might be mediated by preserving mitochondrial ultrastructure and DNA integrity.

Propofol administration improves neurological function associated with inhibition of pro-inflammatory cytokines in adult rats after traumatic brain injury

BackgroundNeurological deficits following traumatic brain injury (TBI) result in dramatic impacts on the survivors, but the effect of propofol and associated mechanism are waiting to be determined. MethodsAdult male Sprague–Dawley rats were randomly assigned into Sham, TBI, TBI+Intralipid and TBI+Propofol group. Modified Feeney method was adopted to generate TBI model from free hammer fall injury, and animals in TBI+Propofol group were immediately treated with propofol administration for 2hours after TBI, rats after TBI without propofol treatment was used as injury control, intralipid as vehicle in propofol was injected in TBI+intralipid group. Then, neurological severity scores (NSS) were evaluated at 1, 3, 7 and 14days. Moreover, the expressions of IL-1β, IL-6 and TNF-α mRNA and protein were examined using quantitative real time-polymerase chain reaction and Western blot, immunohistochemical staining was used to localize cytokines. ResultsThe NSS increased greatly in the rats induced by TBI, while propofol could effectively decreased NSS, confirming the neuroprotective effect of propofol. Moreover, the mRNA expressions of IL-1β, IL-6 and TNF-α, at 1, 3, 7days after operation (dpo), were significantly augmented in the injured cortex, compared with sham one. But there was no difference between TBI and TBI+Intralipid group, but markedly decreased after propofol treatment. Additionally, the protein level of IL-1β, IL-6 and TNF-α in four groups determined by Western blot and immunohistochemistry showed the similar change with mRNA expression. ConclusionPropofol treatment could elicit a robust neuroprotective response, resulting in significant neurological function improvement for TBI rats, which was independent with intralipid. The underlying molecular mechanism may be partially associated with an inhibition of pro-inflammatory cytokines.

Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial

BackgroundParenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations.ObjectiveTo confirm the safety and demonstrate efficacy of the immediate introduction of the recommended daily intake of amino acids (Imm-RDI) and soya bean oil, medium-chain triglycerides, olive oil and fish oil lipid in PN to increase non-adipose (lean) body mass and decrease intrahepatocellular lipid (IHCL) content.DesignMulticentre, double-blind, 2 × 2 factorial and randomised controlled trial (RCT).SettingNeonatal units in London and south-east England, UK.ParticipantsExtremely preterm infants born before 31 weeks of gestation without major congenital or life-threatening abnormalities who could to be randomised to receive PN within 24 hours of birth.InterventionsInfants were randomised within 24 hours of birth to receive PN containing either high [RDI of amino acids (Imm-RDI)] or low [incremental amino acids (Inc-AA) control] levels of amino acids. In addition, infants were randomised to receive either 20% SMOFlipid®(Fresenius Kabi AG, Richmond Hill, ON, Canada) or 20% Intralipid®(Fresenius Kabi AG, Richmond Hill, ON, Canada) (control). This resulted in four groups: (1) Inc-AA/Intralipid, (2) Inc-AA/SMOFlipid, (3) Imm-RDI/Intralipid and (4) Imm-RDI/SMOFlipid. The intervention was continued until infants were receiving 150 ml/kg/day of enteral feeds for 24 hours.Primary outcome measureFor the amino acid intervention, this was non-adipose or lean body mass measured by magnetic resonance imaging. For the lipid composition intervention, this was IHCL content as measured by hepatic magnetic resonance spectroscopy. Primary outcomes were measured at term age equivalent, between 37 and 44 weeks postmenstrual age.ResultsWe randomised 168 infants born before 31 weeks of gestation. We evaluated outcomes, at term, in 133 infants. There were no significant differences in non-adipose mass between the Imm-RDI and Inc-AA groups [adjusted mean difference 1.0 g, 95% confidence interval (CI) –108 to 111 g] or in levels of IHCLs between the SMOFlipid and Intralipid groups (adjusted mean SMOFlipid to Intralipid ratio 1.1, 95% CI 0.8 to 1.6). Infants receiving the Imm-RDI were more likely than Inc-AA infants to have blood urea nitrogen levels &gt; 7 mmol/l [75% vs. 49% (p &lt; 0.01)] and &gt; 10 mmol/l [49% vs. 18% (p &lt; 0.01)]. Furthermore, head circumference at term was smaller in the Imm-RDI group (mean difference –0.8 cm, 95% CI –1.5 to –0.1 cm;p = 0.02). There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, weight, length and mortality.LimitationsNot all eligible babies were available for recruitment, as pharmacy staff trained in clinical trial procedures were unavailable at weekends in three of the four centres. We were able to assess brain volumes in only one-third of participants, as imaging was carried out while the participants were sleeping naturally and we measured primary outcomes first and continued to brain imaging only if the infant remained asleep.ConclusionsImmediate delivery of the recommended daily intake of parenteral amino acids does not benefit body composition or growth to term and may be harmful; SMOFlipid does not affect IHCL content.Future workThe long-term functional outcomes of early administration of RDI of amino acids and the use of SMOFlipid, including neurodevelopment, body composition and metabolic health, should be evaluated.Trial registrationCurrent Controlled Trials ISRCTN29665319 and EudraCT 2009-016731-34.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid.

To examine whether SMOFlipid prevents progression of intestinal failure-associated liver disease (IFALD) in parenteral nutrition (PN)-dependent infants with early IFALD (conjugated bilirubin 17-50 µmol/L, 1-3 mg/dL). Pilot multicenter blinded randomized controlled trial comparing SMOFlipid with Intralipid. Patients received the trial lipid for up to 12 weeks, unless they achieved full enteral tolerance sooner. The primary clinical outcome was the serum conjugated bilirubin. Twenty-four infants (mean age, 6 weeks) participated in the trial (13 Intralipid and 11 SMOFlipid). At the time of trial enrollment, patients in both groups were receiving 90% of their calories by PN. Mean duration on trial was 8 weeks and did not differ according to treatment ( P = .99). At trial conclusion, patients who received SMOFlipid had a lower conjugated bilirubin than those who received Intralipid (mean difference, -59 µmol/L; P = .03). Patients receiving SMOFlipid were also more likely to have a decrease in serum conjugated bilirubin to 0 µmol/L than those in the Intralipid group over the entire observation period (hazard ratio, 10.6; 95%; P = .03). The time to achievement of full enteral tolerance did not differ statistically (hazard ratio, 1.3; P = .59) between the groups. There was no significant difference in safety outcomes between the groups. Compared with Intralipid, SMOFlipid reduces the risk of progressive IFALD in children with intestinal failure. This trial was registered at clinicaltrials.gov as NCT00793195.

Effects of intralipid and caffeic acid phenyl esther (CAPE) against hepatotoxicity and nephrotoxicity caused by glyphosate isopropylamine (GI)

This study was aimed to investigate the protective effects of caffeic acid phenyl esther (CAPE) and Intralipid (IL) against hepatotoxicity and nephrotoxicity caused by acute intoxication of glyphosate (N-phosphonomethyl)glycine) (GI) in rats. Forty-nine Wistar Albino rats were randomly divided into seven groups as: I, Control; II, Intralipid (IL) (18.6 mL/kg, orally); III, CAPE (10 µmol/kg, intraperitoneally); IV, GI (4 mg/kg/day, intraperitoneally); V, GI + IL; VI, GI+CAPE; and VII, GI + IL + CAPE. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured in serum samples. Tissues were analyzed with hematoxylin and eosin (H&amp;E) staining protocol. Bcl-2, Bax, and caspase-3 were evaluated by immunohistochemical method. The results revealed that, in hepatic tissues, the TAS levels were lower and the TOS levels were higher in the GI group compared to other groups. In renal tissues, the TAS levels were significantly lower in the GI group than in the control, IL, CAPE, and GI + IL + CAPE groups. The TOS levels were significantly higher in the GI group than in the control group. Moreover, histopathological analysis revealed severe hepatotoxicity in the GI group. In the GI + CAPE + IL group, hepatotoxicity recovered significantly. Nephrotoxicity was also observed in the GI group and moderately reduced in the GI + CAPE group. Biochemical results were confirmed by histopathologic examination. The results also revealed that CAPE and IL, due to their antioxidant effects, have a decreasing effect against both hepatotoxicity and nephrotoxicity caused by GI. Therefore, CAPE and IL may function as potential agents for supportive therapy since they decrease organ damage, or may facilitate the therapeutic effects of the routine treatment of patients with GI poisoning.

Emulsified Isoflurane Produces Cardioprotection against Severe Burn-Induced Cardiac Shock

Background: Cardiac shock, occurring at the early stage of severe burns, causes cardiac insufficiency. Cardiac dysfunction after severe burn is associated with myocardial injury. Emulsified isoflurane (EIso) has been demonstrated to have cardioprotective effect against ischemia and reperfusion injury. Whether burn-induced cardiac dysfunction is influenced by EIso is currently unknown. We tested the hypothesis that EIso decreases myocardial damage in rat model with severe burn.Methods: In an in vivo study, sprague dawley rats, weighting 250-300 g, were randomized into four groups: 1) sham-burn group (sham, saline), 2) burn group (CON, saline, 30% total body surface area [TBSA] full-thickness burn), 3) burn+30% intralipid (IL, vehicle for EIso) group, and 4) burn+8% EIso of 1.5 ml/kg (EIso) group. Lactated ringers solution was immediately injected intraperitoneally to all rats after burn injury according to Parkland formula (4.0 ml/kg/1%TBSA), followed by continuous intravenous infusion of isovolumetric saline, intralipid and EIso for 30 minutes in each group. Hemodynamic parameters were constantly monitored throughout the experiment. 3 hours post-burn, hearts were excised for determination of enzyme activity and apoptosis.Results: Under baseline conditions, no significant differences in systemic hemodynamics were observed among the groups. Heart rate decreased after burn injury in the CON, EIso and IL groups. Compared with the sham group, burn injury was accompanied by a reduction of systolic function in left ventricular systolic pressure (LVSP) and maximum rate of increase in left ventricular pressure (dP/dtmax), and an increase in maximum rate of decrease in left ventricular pressure (-dP/dtmax). 2 to 3 hours after burn, EIso attenuated decreases in LVSP and dP/dtmax. Malondialdehyde (MDA) was reduced from 2.55±0.29 mmol/mg prot in CON group and 2.21±0.23 in IL group to 1.79±0.28 in EIso group (P<0.01 vs. CON and P<0.05 vs. IL). EIso also increased the level of superoxide dismutase (SOD) (162.5±10.5 U/mg prot), compared with CON group (140.4 ±12.1, P<0.01). However, there was no difference regarding the changes of apoptotic protein (Bcl-2 and Bax) expression among groups. Meanwhile, no apoptotic cells were detected throughout the experiment in any groups.Conclusions: EIso could protect hearts against severe burns during the early stage post-burn, which may be independent from the involvement of apoptosis. Citation: Zhao-Yang Hu, Ya-Dong Fang, Ze-Gang Yin, Bai-Xing Li, Yue-Sheng Huang, Jin Liu. Emulsified isoflurane produces cardioprotection against severe burn-induced cardiac shock. J Anesth Perioper Med 2016; 3: 11-17. doi: 10.24015/JAPM.2016.0002This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Analysis of the temporal regression of the QRS widening induced by bupivacaine after intralipid administration. Study in an experimental porcine model

ObjectiveThe principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. Material and methodsTwelve pigs were anesthetized with intravenous sodium thiopental 5mgkg−1 and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4–6mgkg−1 was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5mLkg−1 of IL over 1min, followed by an infusion of 0.25mLkgmin−1. Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30min after Intralipid/saline administration. ResultsBupivacaine (4.33±0.81mg/kg in IL group and 4.66±1.15mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184±62% in IL group, and 230±56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After 10min of the administration of IL, the mean QRS interval decreased to 132±56% vs. 15±76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. ConclusionIntralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10min. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored.