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Background: Traditional models of shock classify severity based on the volume of hemorrhage. Clinically, hemorrhage occurs at a variable rate, usually slowing as blood pressure drops; however most animal experimental models use a constant rate of hemorrhage. Our hypothesis was that rapid bleeding followed by slower bleeding using a fixed total volume would result in a greater physiologic insult., Materials and Methods: Yorkshire pigs (S and S Farms, Ranchita, CA) underwent placement of jugular and femoral catheters after anesthesia. All animals were hemorrhaged a total of 30 mL/kg. The animals were divided into constant rate hemorrhage over 10 min (Constant-10) (3 mL/kg/min), constant rate hemorrhage over 20 min (Constant-20) (1.5 mL/kg/min), or a varying rate of hemorrhage of 2.15 mL/kg/min over 7 min, and then 1.15 mL/kg/min over the remaining 13 min (Physiologic-20). Shock, mean arterial pressure (MAP) < or = 20 mmHg, was maintained for 60 min. Resuscitation was performed with Ringer's lactate (RL) and shed blood (2:1 ratio), until shed blood was exhausted and then only RL to maintain a MAP > or =60 mmHg for 3 h., Results: Physiologic-20 shock resulted in significantly increased maximal heart rate, peak serum lactate, and volume of required RL resuscitation. Adequacy of resuscitation was ensured by MAP, urine output, and clearance of serum lactate., Conclusions: A more physiologic method of fixed volume hemorrhagic shock results in a significantly increased physiologic response as demonstrated by increased volume of fluid resuscitation. This differential physiologic response may represent an improved hemorrhagic shock model, and could have implications for future hemorrhagic shock studies.

Purpose: To evaluate the healing process of gastric suture in rats using hydroalcoholic aroeira (Schinus terebinthifolius Raddi) extract., Methods: Forty adult male rats, divided into two groups of 20 animals were operated and named as follows: aroeira group (Ga), and the control group (Gc). Each group was divided into two subgroups (SG) of 10 animals (SGa and SGc) according to the time of provoked death (three and seven days). The same surgical procedure was performed in all animals consisting in incision and simple suture of the stomach (Prolene(R) 6-0). The only difference was on the type of medical treatment. The aroeira group received a single 100 mg/kg of aroeira extract in an intraperitoneal dose and the animals from the control group received the same quantity in milliliters (ml) of the isotonic saline solution. The evaluated parameters were: macroscopic alterations, microscopic healing process and toleration to atmospheric air insufflation., Results: All animals had good healing process of abdominal wall with no clinical evidence of infection, dehiscence, abscesses and peritonitis. Both groups presented adherences to gastric suture line area with surrounding organs, mainly the liver, lower intestines and the abdominal wall. Microscopic analysis showed only chronic inflammation significant difference between the aroeira and control groups on the third day of observation. Resistance tests did not present significant statistical differences in the studied groups., Conclusion: The use of aroeira (Schinus terebinthifolius Raddi) hydro-alcoholic extract did not alter the stomach healing process, considered on macroscopic, tensiometric and microscopic assessment.

Background: Endotoxemia is accompanied by pro-inflammatory cytokine production, generation of reactive oxygen species, and end-organ injury. Pentoxifylline (PTX), a methylxanthine derivative and phosphodiesterase inhibitor, is known for its anti-inflammatory properties, including down-regulation of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha synthesis. Its effects on liver function and hepatic histology following acute endotoxemia have not been investigated fully. We hypothesized that PTX would preserve liver architecture and function after intravenous lipopolysaccharide (LPS) injection., Methods: Anesthetized Sprague-Dawley rats received an i.v. bolus injection of LPS (5 mg/kg), LPS + PTX (25 mg/kg), or saline (sham). Plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNF-alpha, IL-6, and nitrite were measured at different time points after LPS injection. Liver injury was graded according to a scoring system in a blinded fashion from 0 (normal) to 4 (severe) for hepatocellular necrosis, hemorrhage, and parenchymal and sinusoidal inflammatory infiltrates. Neutrophil infiltration was measured by counting myeloperoxidase (MPO)-positive stained cells. Nuclear factor (NF)-kappaB p-65 was measured by counting positive stained nuclei of hepatocytes and Kupffer cells (KC). Inducible nitric oxide synthase (iNOS) was evaluated by positively stained KC. Data are presented as mean +/- SEM. Analysis of variance with p < 0.05 was considered statistically significant., Results: Animals treated with PTX showed a significant reduction in liver injury score and neutrophil infiltration. Treatment with PTX significantly decreased TNF-alpha, IL-6, and the concentrations of AST and ALT when compared to LPS alone. In addition, a significant decrease in NF-kappaB-positive staining in hepatocytes and KC, as well as in KC iNOS immunostaining was observed in PTX-treated animals compared to the LPS group., Conclusions: Pentoxifylline downregulates the inflammatory response significantly and decreases liver injury in acute endotoxemia.

Background: Excessive production of reactive oxygen species by PMN is associated with tissue damage during inflammation. LPS interacts with the cell surface receptor CD14, which generates transmembrane signals through Toll-like protein 4 leading to mitogen activated protein kinase (MAPK) p38 activation, cytokine synthesis, PMN beta2-integrin expression and oxidative burst. Phosphodiesterase inhibition decreases proinflammatory cytokine production and tissue injury after LPS challenge. Its effects on PMN function after LPS stimulation, however, have not been fully investigated. We hypothesized that LPS-induced TNF-alpha synthesis and subsequent PMN beta2-integrin expression and oxidative burst are downregulated by concomitant treatment with the non-specific phosphodiesterase inhibitor pentoxifylline (PTX)., Methods: Whole blood was incubated with HBSS (control), LPS (100 microg/mL), fMLP (1 micromol/L), LPS+PTX (2 mmol/L) and fMLP+PTX for different time intervals at 37C. Oxidative burst, CD14, and CD-11b expression were measured by flow cytometry. Serum TNF-alpha levels were measured by ELISA. In an attempt to localize the site of action of PTX (proximal or distal to PKC) cell surface receptors were bypassed by PMA stimulation (1 microg/mL) and oxidative burst was measured with and without PTX., Results: Up-regulation of CD14 expression was similar in LPS and LPS+PTX groups. LPS stimulation caused a significant increase in PMN oxidative burst, CD11b expression, and TNF-alpha serum levels. In addition, PMA and fMLP stimulation also caused significant increase in oxidative burst compared with controls. Concomitant addition of PTX to LPS led to a significant decrease in PMN oxidative burst (65%; p < 0.0001), PMN CD11b expression (20%; p = 0.012), and TNF-alpha levels (93%; p < 0.0001). Also, PMA- and fMLP-induced PMN oxidative burst were significantly decreased by PTX [77.5% (p < 0.0001) and 50% (p < 0.01), respectively]., Conclusions: These results suggest that PTX-inhibition of oxidative burst occurs distal to PKC and may be either due to direct inhibition of NADPH oxidase or inhibition of MAPK phosphorylation, leading to decreased adhesion molecule expression and TNF-alpha synthesis. Its use in clinical scenarios in which PMN are primed may be of clinical relevance.