PEG-Albumin Plasma Expansion Increases Expression of MCP-1 Evidencing Increased Circulatory Wall Shear Stress: An Experimental Study

Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS), decreasing endothelial nitric oxide (NO) production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb) causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer’s lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa) in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1), a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity

Influences of Forest Structure, Climate and Species Composition on Tree Mortality across the Eastern US

Few studies have quantified regional variation in tree mortality, or explored whether species compositional changes or within-species variation are responsible for regional patterns, despite the fact that mortality has direct effects on the dynamics of woody biomass, species composition, stand structure, wood production and forest response to climate change. Using Bayesian analysis of over 430,000 tree records from a large eastern US forest database we characterised tree mortality as a function of climate, soils, species and size (stem diameter). We found (1) mortality is U-shaped vs. stem diameter for all 21 species examined; (2) mortality is hump-shaped vs. plot basal area for most species; (3) geographical variation in mortality is substantial, and correlated with several environmental factors; and (4) individual species vary substantially from the combined average in the nature and magnitude of their mortality responses to environmental variation. Regional variation in mortality is therefore the product of variation in species composition combined with highly varied mortality-environment correlations within species. The results imply that variation in mortality is a crucial part of variation in the forest carbon cycle, such that including this variation in models of the global carbon cycle could significantly narrow uncertainty in climate change predictions

The Effects of Short-Term Propofol and Dexmedetomidine on Lung Mechanics, Histology, and Biological Markers in Experimental Obesity.

BACKGROUND: Administering anesthetics to the obese population requires caution because of a variety of reasons including possible interactions with the inflammatory process observed in obese patients. Propofol and dexmedetomidine have protective effects on pulmonary function and are widely used in short- and long-term sedation, particularly in intensive care unit settings in lean and obese subjects. However, the functional and biological effects of these drugs in obesity require further elucidation. In a model of diet-induced obesity, we compared the short-term effects of dexmedetomidine versus propofol on lung mechanics and histology, as well as biological markers of inflammation and oxidative stress modulation in obesity. METHODS: Wistar rats (n = 56) were randomly fed a standard diet (lean) or experimental diet (obese) for 12 weeks. After this period, obese animals received sodium thiopental intraperitoneally and were randomly allocated into 4 subgroups: (1) nonventilated (n = 4) for molecular biology analysis only (control); (2) sodium thiopental (n = 8); (3) propofol (n = 8); and (4) dexmedetomidine (n = 8), which received continuous IV administration of the corresponding agents and were mechanically ventilated (tidal volume = 6 mL/kg body weight, fraction of inspired oxygen = 0.4, positive end-expiratory pressure = 3 cm H2O) for 1 hour. RESULTS: Compared with lean animals, obese rats did not present increased body weight but had higher total body and trunk fat percentages, airway resistance, and interleukin-6 levels in the lung tissue (P = 0.02, P = 0.0027, and P = 0.01, respectively). In obese rats, propofol, but not dexmedetomidine, yielded increased airway resistance, bronchoconstriction index (P = 0.016, P = 0.02, respectively), tumor necrosis factor-\u3b1, and interleukin-6 levels, as well as lower levels of nuclear factor-erythroid 2-related factor-2 and glutathione peroxidase (P = 0.001, Bonferroni-corrected t test). CONCLUSIONS: In this model of diet-induced obesity, a 1-hour propofol infusion yielded increased airway resistance, atelectasis, and lung inflammation, with depletion of antioxidative enzymes. However, unlike sodium thiopental and propofol, short-term infusion of dexmedetomidine had no impact on lung morphofunctional and biological variables

Sevoflurane, Compared With Isoflurane, Minimizes Lung Damage in Pulmonary but Not in Extrapulmonary Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: Volatile anesthetics modulate inflammation in acute respiratory distress syndrome (ARDS). However, it is unclear whether they act differently depending on ARDS etiology. We hypothesized that the in vivo and in vitro effects of sevoflurane and isoflurane on lung damage would not differ in pulmonary (p) and extrapulmonary (exp) ARDS. METHODS: Twenty-four Wistar rats were randomized to undergo general anesthesia (1-2 minutes) with sevoflurane and isoflurane. Animals were then further randomized to receive Escherichia coli lipopolysaccharide (LPS) intratracheally (ARDSp) or intraperitoneally (ARDSexp), and 24 hours after ARDS induction, they were subjected to 60 minutes of sevoflurane or isoflurane anesthesia at 1 minimal alveolar concentration. The primary outcome measure was interleukin (IL)-6 mRNA expression in lung tissue. Secondary outcomes included gas exchange, lung mechanics, histology, and mRNA expression of IL-10, nuclear factor erythroid 2-related factor-2 (Nrf2), surfactant protein (SP)-B, vascular cell adhesion molecule-1, epithelial amiloride-sensitive Na+-channel subunits \u3b1 and \u3b3, and sodium-potassium-adenosine-triphosphatase pump subunits \u3b11 (\u3b11-Na,K-ATPase) and \u3b21 (\u3b21-Na,K-ATPase). Additional ARDSp and ARDSexp animals (n = 6 per group) were anesthetized with sodium thiopental but not mechanically ventilated (NV) to serve as controls. Separately, to identify how sevoflurane and isoflurane act on type II epithelial cells, A549 human lung epithelial cells were stimulated with LPS (20 \ub5g/mL) for 24 hours, and SP-B expression was quantified after further exposure to sevoflurane or isoflurane (1 minimal alveolar concentration ) for 60 minutes. RESULTS: In ARDSp, sevoflurane reduced IL-6 expression to a greater degree than isoflurane (P = .04). Static lung elastance (P = .0049) and alveolar collapse (P = .033) were lower in sevoflurane than isoflurane, whereas Nrf2 (P = .036), SP-B (P = .042), and \u3b21-Na,K-ATPase (P = .038) expressions were higher in sevoflurane. In ARDSexp, no significant differences were observed in lung mechanics, alveolar collapse, or molecular parameters between sevoflurane and isoflurane. In vitro, SP-B expression was higher in sevoflurane than isoflurane (P = .026). CONCLUSIONS: Compared with isoflurane, sevoflurane did not affect lung inflammation in ARDSexp, but it did reduce lung inflammation in ARDSp