Oleic Acid Infusion Research Articles

Comparative Study of the Viscosities and Thermal Conductivities of Groundnut and Coconut Oils Dispersed with Graphene Particles Reinforced with Oleic Acid

This study addresses some challenges accrued using mineral oil as cutting fluid and suggest alternatives to suitable, eco-friendly, non-toxic and biodegradable solution using vegetable oil. Oils extracted from vegetables are environmentally friendly, biodegradable, and non-toxic compared with mineral oils. To investigate their optimal use for industrial applications, this study tested base oil's thermal-physical properties (kinematic viscosity and thermal conductivity). Temperatures of 400C and 1000C were considered for kinematic viscosity, and it was improved with the infusion of graphene nanoparticles and oleic acid. The thermal conductivities of the base oils at temperatures of 500C, 600C, and 700C were tested against the addition of graphene nanoparticles at the same temperatures with compositions of 0.001%, 0.003%, and 0.005%. Thermal conductivity of the groundnut oil at 50, 60 and 700C were 0.495, 0.320 and 0.225 Wm-1K-1. The average of the compositions at 50, 60 and 700C were 0.527, 0.33 and 0.25 Wm-1K-1. Compare to coconut oil at 50, 60 and 700C were 0.534, 0.318 and 0.214 Wm-1K-1, and the average of the compositions at 50, 60 and 700C were 0.622, 0.36 and 0.24 Wm-1K-1. Kinematic viscosity increments of coconut oil performed better than groundnut oil at 0.001wt% with 400C is 7.15% and 3.68% for groundnut oil. Groundnut edged coconut oil at 0.003wt% at 400C 17.98% and 11.83%. Similarly, with 0.005wt% at 1000C coconut oil improve with 63.70% compare 59.73% of groundnut oil. Groundnut oil has a higher viscosity index than coconut oil without the addition of nano-lubricant 436.3 and 209. With the infusion of nano-lubricant the average viscosity index for groundnut oil is 535.17 compare to 406.25 of the coconut oils. It can be verified that the infusion of graphene nanoparticles in both oils can be deployed in machining applications to reduce the friction between contacting surfaces and dissipate heat from the cutting zone.

Differential changes in expression of inflammatory mRNA and protein after oleic acid-induced acute lung injury

Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. Methods: Nineteen juvenile female swine were included in the study. ARDS defined by a PaO2/FiO2 ratio < 300 was induced by continuous oleic acid infusion. Arterial blood was drawn before and during oleic acid infusion, and when ARDS was established. Cytokine expression in WBC was analyzed by RT-qPCR and plasma protein expression by ELISA. Results: The median concentration of IFN-γ mRNA was estimated to be 59% (p = 0.006) and of IL-6 to be 44.4% (p = 0.003) of the baseline amount. No significant changes were detected for TNF-α, IL-17, and IL-10 mRNA expression. In contrast, the concentrations of plasma IFN-γ and IL-6 were significantly higher (p = 0.004 and p = 0.048 resp.), and TNF-α was significantly lower (p = 0.006) at ARDS compared to baseline. Conclusions: The change of proinflammatory cytokines IFN-γ and IL-6 expression is different comparing mRNA and plasma proteins at oleic acid-induced ARDS compared to baseline. The migration of cells to the lung may be the cause for this discrepancy.

A Porcine Model of Acute Respiratory Failure with a Continuous Infusion of Oleic Acid

A Porcine Model of Acute Respiratory Failure with a Continuous Infusion of Oleic Acid

Indirect cardiac output assessment in a swine pediatric acute respiratory distress syndrome model

PurposeTo investigate the correlation between volume of carbon dioxide elimination (V̇CO2) and end-tidal carbon dioxide (PETCO2) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model. MethodsRespiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion. ResultsPrior to ARDS induction, mean (SD) CO, V̇CO2, PETCO2, and dead space to tidal volume ratio (Vd/Vt) were 4.16 (1.10) L/min, 103.69 (18.06) ml/min, 40.72 (3.88) mmHg and 0.25 (0.09) respectively. Partial correlation coefficients between average CO, V̇CO2, and PETCO2 were 0.44 (95% confidence interval: 0.18–0.69) and 0.50 (0.18–0.74), respectively. After ARDS induction, mean CO, V̇CO2, PETCO2, and Vd/Vt were 3.33 (0.97) L/min, 113.71 (22.97) ml/min, 50.17 (9.73) mmHg and 0.40 (0.08). Partial correlations between CO and V̇CO2 was 0.01 (−0.31 to 0.37) and between CO and PETCO2 was 0.35 (−0.002 to 0.65). ConclusionARDS may limit the utility of volumetric capnography to monitor CO.

Abstract 185: Regional Oxygen Saturation and Capnography Monitoring During Resuscitation After Cardiac Arrest in a Swine Pediatric ARDS Model

Introduction: Survival and outcomes after cardiac arrest (CA) depend largely on the effectiveness of cardiopulmonary resuscitation (CPR). Traditional invasive methods of monitoring CPR can be challenging out-of-hospital and are lacking in more than 50% of in-hospital pediatric CA. Regional oxygen saturation (rSO 2 ) monitoring with Near Infrared Spectroscopy (NIRS) and volumetric capnography offers a noninvasive approach that could potentially overcome these challenges. Aim: To determine the feasibility and effectiveness of NIRS and volumetric capnography monitoring in a swine model of pediatric hypoxia induced CA. Approach: Juvenile pigs were sedated and mechanically ventilated. Mild to moderate Acute Respiratory Distress Syndrome (ARDS) was induced by continuous oleic acid infusion. Respiratory and hemodynamic variables were monitored using invasive and noninvasive (NIRS and capnography) monitoring to assess efficacy of CPR. Animals were randomized into one of the two groups: High-quality CPR (hqCPR) to achieve coronary perfusion pressure of 25-30 mmHg and low-quality CPR (lqCPR) to achieve coronary perfusion pressure of 10-15 mmHg. Trajectories over time were analyzed using regression analyses. The discriminatory ability to distinguish between groups based on trajectories were analyzed using receiver operating characteristics curve (ROC) analysis. Results: 39 animals (23±3 kg) were included in our study. In the hqCPR group, there are generally higher values for cerebral and renal rSO 2 , ETCO 2 , volume of CO 2 elimination (VCO 2 ), and carotid blood flow, compared to the lqCPR group (p&lt;0.0001). Cerebral and renal rSO 2 values increase over time, while ETCO 2 , VCO 2 , and carotid flow values decrease in the hqCPR group. Cerebral rSO2 had a ROC AUC of 0.76 (95% CI: 0.58-0.94), whereas renal rSO2 had a ROC AUC of 0.54 (95% CI: 0.22-0.87) representing nearly no discrimination ability. ETCO 2 had a ROC AUC of 0.66 (95% CI: 0.49-0.84), whereas VCO 2 had a ROC AUC of 0.62 (95% CI: 0.38-0.85). Conclusions: Higher mean cerebral rSO2 values during CPR might be used to assess quality of CPR effectiveness and provide real-time adjustments as needed. This could guide healthcare providers in optimizing CPR quality and improving outcomes for cardiac arrest patients.

Effect and mechanical mechanism of spontaneous breathing on oxygenation and lung injury in mild or moderate animal ARDS

ObjectiveThe present study aimed to determine the effect and mechanical mechanism of spontaneous breathing during mechanical ventilation on oxygenation and lung injury using Beagles dogs mild or moderate acute respiratory distress syndrome (ARDS) model.MethodsAfter inducing mild or moderate ARDS by infusion of oleic acid, Eighteen Beagles dogs were randomly split into Spontaneous breathing group (BIPAPSB, n = 6), and Complete muscle paralysis group (BIPAPPC, n = 6),Six Beagles without ventilator support comprised the control group. Both groups were ventilated for 8 h under BIPAP mode. High-pressure was titrated TV to 6 ml/kg. A multi-pair esophageal balloon electrode catheter was used to measure respiratory mechanics and electromyogram. End-expiratory lung volume (EELV), gas exchange and respiratory variables were recorded in the process of mechanical ventilation. The contents of Interleukin (IL)-6 and IL-8 in lung tissue were measure using qRT-PCR. Besides, lung injury score was calculated in the end of mechanical ventilation.ResultsBased on the comparable setting of ventilator, BIPAPSB group exhibited higher safety peak transpulmonary pressure, abdominal pressure, EELV and P/F(PaO2/FiO2) than BIPAPPC group, whereas mean transpulmonary pressure, the mRNA levels of the IL-6 and IL-8 in the lung tissues and lung injury score in BIPAPSB group were lower than those in BIPAPPC group.ConclusionIn mild to moderate ARDS animal models, during mechanical ventilation, SB may improve respiratory function and reduce ventilator-induced lung injury. The mechanism may be that spontaneous inspiration up-regulates peak transpulmonary pressure and EELV; Spontaneous expiration decreases mean transpulmonary pressure by up-regulating intra-abdominal pressure, thereby reducing stress and strain.

A novel speckle-tracking echocardiography parameter assessing left ventricular afterload.

Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.

Abomasal infusion of oleic acid and exogenous emulsifier alter fatty acid digestibility and production responses of lactating dairy cows

We evaluated the effects of abomasal infusion of cis-9 C18:1 (oleic acid) and an exogenous emulsifier (polysorbate-C18:1) on fatty acid (FA) digestibility and production responses of dairy cows. Eight rumen-cannulated multiparous cows (96 ± 23 d in milk) were assigned to a 2 × 2 factorial arrangement of treatments in 4 × 4 Latin squares with 18-d periods consisting of 7 d of washout and 11 d of infusion. Treatments were abomasal infusions of water carrier only (CON), 45 g/d oleic acid (OA), 20 g/d polysorbate-C18:1 (T80), or both 45 g/d OA and 20 g/d T80 (OA+T80). The OA treatments were dissolved in ethanol and the T80 treatments in water. To deliver the daily dose for each treatment, the infusate solution was divided into 4 equal infusions per day, occurring every 6 h. Cows were fed the same diet, which contained [% of dry matter (DM)] 30.3% neutral detergent fiber (NDF), 16.3% crude protein, 30% starch, and 3.2% FA (including 1.8% DM from a FA supplement containing 34.4% C16:0 and 47.7% C18:0). Infusion of T80 increased NDF digestibility compared with all other treatments (3.57 percentage units), whereas OA+T80 decreased NDF digestibility compared with CON (3.30 percentage units). Compared with CON, OA (4.90 percentage units) and T80 (3.40 percentage units) increased total FA digestibility, whereas OA+T80 had no effect on total FA digestibility. We did not observe differences between OA and T80 for total FA digestibility. Infusion of OA (3.90 percentage units) and T80 (2.80 percentage units) increased 16-carbon FA digestibility compared with CON. Digestibility of 16-carbon FA did not differ between OA and T80 or between CON and OA+T80. Compared with CON, OA increased (5.60 percentage units) and T80 tended to increase 18-carbon FA digestibility. Digestibility of 18-carbon FA did not differ between OA and T80 or between CON and OA+T80. Compared with CON, all treatments increased or tended to increase the absorption of total and 18-carbon FA. Infusion of OA and T80 increased the yields of milk fat (both increased 0.10 kg/d), 3.5% fat-corrected milk (1.90 and 2.50 kg/d), and energy-corrected milk (1.80 and 2.60 kg/d) compared with CON. We did not observe differences between OA and T80 or between CON and OA+T80 for yields of milk fat, 3.5% fat-corrected milk, or energy-corrected milk. Infusing OA tended to increase plasma insulin concentration compared with CON. Compared with the other treatments, OA+T80 decreased the yield of de novo milk FA (31.3 g/d). Compared with CON, OA tended to increase the yield of de novo milk FA. Compared with OA+T80, CON and OA tended to increase the yield of mixed milk FA, whereas T80 increased it (83 g/d). Compared with CON, all emulsifier treatments increased the yield of preformed milk FA (52.7 g/d). In conclusion, abomasally infusing either 45 g of OA or 20 g of T80 improved digestibility and similarly favored the production parameters of dairy cows. In contrast, providing both (45 g of OA + 20 g of T80) had no additional benefits and moderated the positive responses observed in the individual treatments with OA and T80.

Intestinal Synthesis and Lymphatic Secretion of Apolipoprotein A–IV Vary with Chain Length of Intestinally Infused Fatty Acids in Rats

To evaluate the hypothesis that stimulation of intestinal apolipoprotein (apo) A–IV by dietary fat depends upon assembly and transport of chylomicrons, we examined the effect of duodenal infusion of fatty acids of graded chain length on mucosal synthesis and lymphatic output of lipid and apo A–IV. Rats with duodenal cannulas and mesenteric lymph fistulas were given 8-h duodenal infusions of lipid emulsions containing either butyric (4:0), caprylic (8:0), lauric (12:0), myristic (14:0), stearic (18:0), oleic (18:1), linoleic (18:2) or arachidonic (20:4) acids, or tributyrin, tricaprylin or triolein. Lymph outputs of triglyceride, phospholipid and apo A–IV were measured at 0, 2, 4, 5, 6, 7 and 8 h after the start of lipid infusion. Significant increases in lymph lipid (triglyceride, phospholipid) and apo A–IV output were observed in response to long-chain fatty acids (14:0, 18:0, 18:1, 18:2, 20:4) or triolein; short- or medium-chain fatty acids (4:0, 8:0, 12:0) or tributyrin or tricaprylin produced no significant increase in lymph lipid output above basal levels. Similarly, increased jejunal mucosal synthesis of apo A–IV was observed in response to duodenal infusion of oleic acid but not butyric or caprylic acid. These results provide direct support for the hypothesis that stimulation of apo A–IV by dietary fat depends upon transport of absorbed lipid via chylomicrons in lymph.

Individualised flow-controlled versus pressure-controlled ventilation in a porcine oleic acid-induced acute respiratory distress syndrome model.

A continuous gas flow provided by flow-controlled ventilation (FCV) facilitates accurate dynamic compliance measurement and allows the clinician to individually optimise positive end-expiratory and peak pressure settings accordingly. The aim of this study was to compare the efficiency of gas exchange and impact on haemodynamics between individualised FCV and pressure-controlled ventilation (PCV) in a porcine model of oleic acid-induced acute respiratory distress syndrome (ARDS). Randomised controlled interventional trial conducted on 16 pigs. Animal operating facility at the Medical University Innsbruck. ARDS was induced in lung healthy pigs by intravenous infusion of oleic acid until moderate-to-severe ARDS at a stable Horowitz quotient (PaO 2 FiO 2-1 ) of 80 to 120 over a period of 30 min was obtained. Ventilation was then either performed with individualised FCV ( n = 8) established by compliance-guided pressure titration or PCV ( n = 8) with compliance-guided titration of the positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 6 ml kg -1 over a period of 2 h. Gas exchange parameters were assessed by the PaO 2 FiO 2-1 quotient and CO 2 removal by the PaCO 2 value in relation to required respiratory minute volume. Required catecholamine support for haemodynamic stabilisation was measured. The FCV group showed significantly improved oxygenation [149.2 vs. 110.4, median difference (MD) 38.7 (8.0 to 69.5) PaO 2 FiO 2-1 ; P = 0.027] and CO 2 removal [PaCO 2 7.25 vs. 9.05, MD -1.8 (-2.87 to -0.72) kPa; P = 0.006] at a significantly lower respiratory minute volume [8.4 vs. 11.9, MD -3.6 (-5.6 to -1.5) l min -1 ; P = 0.005] compared with PCV. In addition, in FCV-pigs, haemodynamic stabilisation occurred with a significant reduction of required catecholamine support [norepinephrine 0.26 vs. 0.86, MD -0.61 (-1.12 to -0.09) μg kg -1 min -1 ; P = 0.037] during 2 ventilation hours. In this oleic acid-induced porcine ARDS model, individualised FCV significantly improved gas exchange and haemodynamic stability compared with PCV. Protocol no.: BMBWF-66.011/0105-V/3b/2019).

Intestinal GPR119 activation by microbiota-derived metabolites impacts feeding behavior and energy metabolism

ObjectiveThe gastrointestinal tract affects physiological activities and behavior by secreting hormones and generating signals through the activation of nutrient sensors. GPR119, a lipid sensor, is indirectly involved in the secretion of incretins, such as glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, by enteroendocrine cells, while it directly stimulates insulin secretion by pancreatic beta cells. Since GPR119 has the potential to modulate metabolic homeostasis in obesity and diabetes, it has attracted interest as a therapeutic target. However, previous studies have shown that the deletion of Gpr119 in mice does not affect glucose homeostasis and appetite in either basal or high-fat diet-fed conditions. Therefore, the present study aimed to explore the role of GPR119 signaling system in energy metabolism and feeding behavior in mice. MethodsGpr119 knockout (KO) mice were generated using CRISPR-Cas9 gene-editing technology, and their feeding behavior and energy metabolism were evaluated and compared with those of wild type (WT) mice. ResultsUpon inducing metabolic stress via food deprivation, Gpr119 KO mice exhibited lower blood glucose levels and a higher body weight reduction compared to WT mice. Although food intake in WT and KO mice were similar under free-feeding conditions, Gpr119 KO mice exhibited increased food intake when they were refed after 24 h of food deprivation. Further, food-deprived Gpr119 KO mice presented shorter post-meal intervals and lower satiety for second and later meals during refeeding, resulting in increased food intake. Associated with this meal pattern, levels of oleoylethanolamide (OEA), an endogenous agonist of GPR119, in the luminal contents of the distal gastrointestinal tract were elevated within 2 h after refeeding. The large-intestinal infusion of OEA prolonged post-meal intervals and increased satiety in the first meal, but not the second meal. On the other hand, infusion of oleic acid increased cecal OEA levels at 2 h from the beginning of infusion, while prolonging post-meal intervals and increasing satiety on the meals that occurred approximately 2 h after the infusion. Cecal OEA levels were low in antibiotic-treated mice, suggesting that the gut microbiota partially synthesizes OEA from oleic acid. ConclusionsCollectively, our results indicate that the activation of gastrointestinal GPR119 by microbiota-produced OEA derived from oleic acid is associated with satiety control and energy homeostasis under energy shortage conditions.

Comparison of two porcine acute lung injury models: a post-hoc analysis

BackgroundAcute respiratory distress syndrome (ARDS) is a common disease in intensive care medicine. Despite intensive research, mortality rates are high, not even in COVID-19 ARDS. Thereby, pigs offer some advantages to study the characteristics of ARDS. Many different ARDS models exist. Most of the articles published focused on histopathological and microscopic lung alterations to identify the most suitable animal ARDS model. “Macroscopic” observations and descriptions are often missing. Therefore, we performed a post-hoc comparison of two common ARDS models for pigs: lipopolysaccharide (LPS) vs. a double-hit model (bronchoalveolar lavage + oleic acid infusion). We investigated hemodynamic, spirometric and laboratory changes as another main clinical part of ARDS.ResultsThe groups were compared by two-way analysis of variance (ANOVA) with a post-hoc Student–Newman–Keuls test. A p value lower than 0.05 was accepted as significant. All animals (n = 8 double-hit ARDS; n = 8 LPS ARDS) survived the observation period of 8 h. ARDS induction with reduced oxygen indices was successful performed in both models (76 ± 35/225 ± 54/212 ± 79 vs. 367 ± 64; T0/T4/T8 vs. BLH for double-hit; 238 ± 57/144 ± 59 vs. 509 ± 41; T4/T8 vs. BLH for LPS; p < 0.05). ARDS induced with LPS leads to more hemodynamic (mean arterial pulmonary pressure 35 ± 3/30 ± 3 vs. 28 ± 4/23 ± 4; T4/T8 LPS vs. double-hit; p < 0.05; doses of norepinephrine 1.18 ± 1.05 vs. 0.11 ± 0.16; LPS vs. double-hit for T8; p < 0.05) and inflammatory (pulmonary IL-6 expression: 2.41e−04 ± 1.08e−04 vs. 1.45e−05 ± 7.26e−06; LPS vs. double-hit; p < 0.05) alterations. ARDS induced by double-hit requires a more invasive ventilator strategy to maintain a sufficient oxygenation (PEEP at T4: 8 ± 3 vs. 6 ± 2; double-hit vs. LPS; p < 0.05).ConclusionsBoth animal ARDS models are feasible and are similar to human presentation of ARDS. If your respiratory research focus on hemodynamic/inflammation variables, the LPS-induced ARDS is a feasible model. Studying different ventilator strategies, the double-hit ARDS model offers a suitable approach.

Abomasal infusion of oleic acid increases fatty acid digestibility and plasma insulin of lactating dairy cows

Our objective was to determine whether abomasal infusions of increasing doses of oleic acid (cis-9 C18:1; OA) improved fatty acid (FA) digestibility and milk production of lactating dairy cows. Eight rumen-cannulated multiparous Holstein cows (138 d in milk ± 52) were randomly assigned to treatment sequence in a replicated 4 × 4 Latin square design with 18-d periods consisting of 7 d of washout and 11 d of infusion. Production and digestibility data were collected during the last 4 d of each infusion period. Treatments were 0, 20, 40, or 60 g/d of OA. We dissolved OA in ethanol before infusions. The infusate solution was divided into 4 equal infusions per day, occurring every 6 h, delivering the daily cis-9 C18:1 for each treatment. Animals received the same diet throughout the study, which contained (percent diet dry matter) 28% neutral detergent fiber, 17% crude protein, 27% starch, and 3.3% FA (including 1.8% FA from a saturated FA supplement containing 32% C16:0 and 52% C18:0). Infusion of OA did not affect intake or digestibility of dry matter and neutral detergent fiber. Increasing OA from 0 to 60 g/d linearly increased the digestibility of total FA (8.40 percentage units), 16-carbon FA (8.30 percentage units), and 18-carbon FA (8.60 percentage units). Therefore, increasing OA linearly increased absorbed total FA (162 g/d), 16-carbon FA (26.0 g/d), and 18-carbon FA (127 g/d). Increasing OA linearly increased milk yield (4.30 kg/d), milk fat yield (0.10 kg/d), milk lactose yield (0.22 kg/d), 3.5% fat-corrected milk (3.90 kg/d), and energy-corrected milk (3.70 kg/d) and tended to increase milk protein yield. Increasing OA did not affect the yield of mixed milk FA but increased yield of preformed milk FA (65.0 g/d) and tended to increase the yield of de novo milk FA. Increasing OA quadratically increased plasma insulin concentration with an increase of 0.18 μg/L at 40 g/d OA, and linearly increased the content of cis-9 C18:1 in plasma triglycerides by 2.82 g/100 g. In conclusion, OA infusion increased FA digestibility and absorption, milk fat yield, and circulating insulin without negatively affecting dry matter intake. In our short-term infusion study, most of the digestion and production measurements responded linearly, indicating that 60 g/d OA was the best dose. Because a quadratic response was not observed, improvements in FA digestibility and production might continue with higher doses of OA, which deserves further attention.

Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS).

Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial infusion of oleic acid, infusion of endotoxins or bacteria, cecal ligation and puncture, various pneumonia models, lung ischemia/reperfusion models and, of course, surfactant depletion models, among others. Surfactant depletion produces a rapid, reproducible deterioration of pulmonary gas exchange and hemodynamics and can be induced in anesthetized pigs using repeated lung lavages with 0.9% saline (35 mL/kg body weight, 37 °C). The surfactant depletion model supports investigations with standard respiratory and hemodynamic monitoring with clinically applied devices. But the model suffers from a relatively high recruitability and ventilation with high airway pressures can immediately reduce the severity of the injury by reopening atelectatic lung areas. Thus, this model is not suitable for investigations of ventilator regimes that use high airway pressures. A combination of surfactant depletion and injurious ventilation with high tidal volume/low positive end-expiratory pressure (high Tv/low PEEP) to cause ventilator induced lung injury (VILI) will reduce the recruitability of the resulting lung injury. The advantages of a timely induction and the possibility to perform experimental research in a setting comparable to an intensive care unit are preserved.

Early restrictive fluid resuscitation has no clinical advantage in experimental severe pediatric acute respiratory distress syndrome.

Intravenous fluids are widely used to treat circulatory deterioration in pediatric acute respiratory distress syndrome (PARDS). However, the accumulation of fluids in the first days of PARDS is associated with adverse outcome. As such, early fluid restriction may prove beneficial, yet the effects of such a fluid strategy on the cardiopulmonary physiology in PARDS are unclear. In this study, we compared the effect of a restrictive with a liberal fluid strategy on a hemodynamic response and the formation of pulmonary edema in an animal model of PARDS. Sixteen mechanically ventilated lambs (2-6 wk) received oleic acid infusion to induce PARDS and were randomized to a restrictive or liberal fluid strategy during a 6-h period of mechanical ventilation. Transpulmonary thermodilution determined extravascular lung water (EVLW) and cardiac output (CO). Postmortem lung wet-to-dry weight ratios were obtained by gravimetry. Restricting fluids significantly reduced fluid intake but increased the use of vasopressors among animals with PARDS. Arterial blood pressure was similar between groups, yet CO declined significantly in animals receiving restrictive fluids (P = 0.005). There was no difference in EVLW over time (P = 0.111) and lung wet-to-dry weight ratio [6.1, interquartile range (IQR) = 6.0-7.3 vs. 7.1, IQR = 6.6-9.4, restrictive vs. liberal, P = 0.725] between fluid strategies. Both fluid strategies stabilized blood pressure in this model, yet early fluid restriction abated CO. Early fluid restriction did not limit the formation of pulmonary edema; therefore, this study suggests that in the early phase of PARDS, a restrictive fluid strategy is not beneficial in terms of immediate cardiopulmonary effects.

Nutrient infusion in the dorsal vagal complex controls hepatic lipid and glucose metabolism in rats

SummaryHypothalamic regulation of lipid and glucose homeostasis is emerging, but whether the dorsal vagal complex (DVC) senses nutrients and regulates hepatic nutrient metabolism remains unclear. Here, we found in rats DVC oleic acid infusion suppressed hepatic secretion of triglyceride-rich very-low-density lipoprotein (VLDL-TG), which was disrupted by inhibiting DVC long-chain fatty acyl-CoA synthetase that in parallel disturbed lipid homeostasis during intravenous lipid infusion. DVC glucose infusion elevated local glucose levels similarly as intravenous glucose infusion and suppressed hepatic glucose production. This was independent of lactate metabolism as inhibiting lactate dehydrogenase failed to disrupt glucose sensing and neither could DVC lactate infusion recapitulate glucose effect. DVC oleic acid and glucose infusion failed to lower VLDL-TG secretion and glucose production in high-fat fed rats, while inhibiting DVC farnesoid X receptor enhanced oleic acid but not glucose sensing. Thus, an impairment of DVC nutrient sensing may lead to the disruption of lipid and glucose homeostasis in metabolic syndrome.

Influence of unsaturated to saturated ratio of fatty acids reaching the duodenum on postruminal digestion of stearic acid in Holstein steers fed a high-fat finishing diet.

Objective:To evaluate the influence of the unsaturated to saturated ratio of fatty acids (FAs) reaching the duodenum on postruminal digestion of FAs, mainly focused on stearic acid (C18:0).Materials and Methods:Six Holstein steers [208 ± 3 kg initial live weight (LW)] with cannulas in the abomasum and proximal duodenum were used in a replicated 3 × 3 Latin square design. Steers were fed a fixed amount of a basal steam-flaked corn-based diet containing 8% supplemental fat and were daily infused via abomasum with 0, 67, and 165 gm oleic acid (C18:1). The experiment lasted for 42 days.Results:The daily total FA (TFA) intake (dietary FA intake plus abomasal infusion of oleic acid) represented a 1.78, 2.10, and 2.56 gm TFA/kg LW ratio. The unsaturated to saturated ratio of FAs entering the duodenum increased (p < 0.01) as level C18:1 infusion into the abomasum increased. Infusion of C18:1 tended (quadratic component, p = 0.07) to improve postruminal TFA digestion, being maximal for the 67 gm/day infusions. This increase in TFA digestion was due to increased (quadratic component, p = 0.03) postruminal C18:0 digestion (postruminal digestion of the other FAs was not different, p ≥ 0.13). Conclusion:Increasing the unsaturated to saturated ratio of FAs entering the small intestine will enhance intestinal C18:0 digestion. This positive effect is expected to be more likely beneficial when FA intake is high (and thus, the duodenal flow of FA is high), but this benefit looks diminished when the quantity of TFA reaching the intestine exceeds the proportion of 2.13 gm FA/kg LW.

Mechanical Ventilation with Room Air is Feasible in a Moderate Acute Respiratory Distress Syndrome Pig Model - Implications for Disaster Situations and Low-Income Nations.

Patients with respiratory failure are usually mechanically ventilated, mostly with fraction of inspired oxygen (FiO2) > 0.21. Minimizing FiO2 is increasingly an accepted standard. In underserved nations and disasters, salvageable patients requiring mechanical ventilation may outstrip oxygen supplies. The hypothesis of the present study was that mechanical ventilation with FiO2 = 0.21 is feasible. This assumption was tested in an Acute Respiratory Distress Syndrome (ARDS) model in pigs. Seventeen pigs were anesthetized, intubated, and mechanically ventilated with FiO2 = 0.4 and Positive End Expiratory Pressure (PEEP) of 5cmH2O. Acute Respiratory Distress Syndrome was induced by intravenous (IV) oleic acid (OA) infusion, and FiO2 was reduced to 0.21 after 45 minutes of stable moderate ARDS. If peripheral capillary oxygen saturation (SpO2) decreased below 80%, PEEP was increased gradually until maximum 20cmH2O, then inspiratory time elevated from one second to 1.4 seconds. Animals developed moderate ARDS (mean partial pressure of oxygen [PaO2]/FiO2 = 162.8, peak and mean inspiratory pressures doubled, and lung compliance decreased). The SpO2 decreased to <80% rapidly after FiO2 was decreased to 0.21. In 14/17 animals, increasing PEEP sufficed to maintain SpO2 > 80%. Only in 3/17 animals, elevation of FiO2 to 0.25 after PEEP reached 20cmH2O was needed to maintain SpO2 > 80%. Animals remained hemodynamically stable until euthanasia one hour later. In a pig model of moderate ARDS, mechanical ventilation with room air was feasible in 14/17 animals by elevating PEEP. These results in animal model support the potential feasibility of lowering FiO2 to 0.21 in some ARDS patients. The present study was conceived to address the ethical and practical paradigm of mechanical ventilation in disasters and underserved areas, which assumes that oxygen is mandatory in respiratory failure and is therefore a rate-limiting factor in care capacity allocation. Further studies are needed before paradigm changes are considered.

Histopathological Evidence of Multiple Organ Damage After Simulated Aeromedical Evacuation in a Swine Acute Lung Injury Model

Rapid aeromedical evacuation (AE) is standard of care in current conflicts. However, not much is known about possible effects of hypobaric conditions. We investigated possible effects of hypobaria on organ damage in a swine model of acute lung injury. Lung injury was induced in anesthetized swine via intravenous oleic acid infusion. After a stabilization phase, animals were subjected to a 4 hour simulated AE at 8000feet (HYPO). Control animals were kept at normobaria. After euthanasia and necropsy, organ damage was assessed by combined scores for hemorrhage, inflammation, edema, necrosis, and microatelectasis. Hemodynamic, neurological, or hematologic measurements were similar prior to transport. Hemodynamic instability became apparent during the last 2 hours of transport in the HYPO group. Histological injury scores in the HYPO group were higher for all organs (lung, kidney, liver, pancreas, and adrenal glands) except the brain, with the largest difference in the lungs (P<0.001). Swine with mild acute lung injury subjected to a 4 hour simulated AE showed more injury to most organs and, in particular, to the lungs compared with ground transport. This may exacerbate otherwise subclinical pathology and, eventually, manifest as abnormalities in gas exchange or possibly end-organ function.

174-OR: Dorsal Vagal Complex Is a Site for Brain Lipid Sensing to Regulate Lipid Homeostasis

Obesity and diabetes are characterized by dyslipidemia due partly to an overproduction of hepatic triglyceride-rich very-low-density lipoproteins (VLDL-TG). The hypothalamus regulates whole-body lipid homeostasis in rodents but whether extra-hypothalamic brain regions can impact lipid homeostasis remain unclear. We here assessed whether the dorsal vagal complex (DVC), a region in the brainstem which contains a circumventricular organ termed the area postrema, as well as the nucleus of the solitary tract and the dorsal motor nucleus of the vagus, senses oleic acids to regulate whole-body lipid homeostasis. We first surgically implanted a guide cannula into the DVC of male 280-300g rats for vehicle (3% cyclodextrin in saline) or oleic acid (1 mM dissolved in vehicle) infusion, followed by catheter placements (7 days after) in the left carotid artery and right jugular vein for sampling and infusion. After an additional 5 days of recovery, 10h-fasted rats received either vehicle or oleic acid pre-infusion to the DVC for 10 min, and DVC infusion was maintained for an additional 150 min after an i.v. injection of poloxamer (600 mg/kg; a lipoprotein lipase inhibitor), while plasma samples were collected every 15 min for TG measurement. The rate of plasma TG appearance as a function of time (slope) reflects the rate of VLDL-TG secretion in the current experimental context. DVC oleic acid vs. vehicle infusion (0.33 ul/h) lowered VLDL-TG secretion (mM/min) in healthy rats (0.032±0.003, n=7 vs. 0.049±0.006, n=5; p&amp;lt;0.001), but interestingly failed to do so in high-fat fed rats. Taken together, our findings indicate that: (i) the DVC is a novel site of fatty acid sensing that impacts whole-body lipid homeostasis by regulating hepatic VLDL-TG secretion, and (ii) a disruption in DVC fatty acid sensing may contribute to the overproduction of hepatic VLDL-TG and a disruption in lipid homeostasis in obesity and diabetes. Disclosure B. Batchuluun: None. T. Waise: None. J.T. Yue: None. T.K. Lam: None. Funding Canadian Institutes of Health Research