when compared with primary anastomosis, as it diminishes intestineischemia time, provides sufficient blood supply, maintainshemodynamics stable, and improves early survival rate.

doi:10.1016/j.jcrc.2008.03.023

A closed loop model of pulmonary gas exchange

Angela Reynolds, Gilles Clermont, G. Bard ErmentroutDepartment of Mathematics, University of Pittsburgh, Scaife 606B,Pittsburgh, PA 15260Department of Critical Care, University of Pittsburgh, Scaife 606B,Pittsburgh, PA 15260

Objectives: To model acute lung injury (ACI), we previouslydeveloped a partial differential equation (PDE) model of gasexchange and inflammation on a respiratory unit (RU). We increasebiological fidelity by incorporating metabolism. We explored thecomputational and theoretical challenges of this more realisticclosed loop system of gas exchange under inflammatory stress.Method: First, we added the loss of O2 and gain of CO2 duringmetabolism to the PDE model creating time-dependent boundaryconditions on pulmonary arterial PO2 and PCO2. Then, the PDEmodel for gas exchange and inflammation on a single RU wassimplified mathematically to a system of ordinary differentialequations. The model was reduced such that arterial PO2 and PCO2reflect the combined effects of metabolism and inflammation.Computational gains allow themodel to operate in a closed loop, andwith more biological fidelity.Results: The output of the ordinary differential equation full lungmodel (multiple linked RUs) matches those seen in the PDE fullmodel when heterogeneity of the lung is introduced via a normaldistribution of tidal volumes over the total number of RUs. Thereduced form of the RU allows heterogeneity in the full lung bychanging both alveolar ventilation and perfusion. As with theprevious model, we see the shunting is a major contributor to thereduction of PO2 during inflammation.Conclusions: The reduction of our previous model is the final stepin developing a useable multiscale model of the lung. The results ofthis reduced multi-RU model are comparable to time courses ofACI. This model will be linked with an organ model to explore thespread of inflammation.

doi:10.1016/j.jcrc.2008.03.024

Mesenteric microcirculatory dysfunction associated with

indigenous bacterial translocation after intestinal obstruction

and ischemia in rats

P. Sannomiya, F.L. Zanoni, S. Benabou, K.V. Greco, A.C. Moreno,J.W.M.C. Cruz, F.P. Filgueira, M.B. Martinez, L.F. Poli deFigueiredo, M. Rocha e SilvaInstitute of Heart (InCor), LIM-11, University of São Paulo MedicalSchool, 05403-000 São Paulo, Brazil

Objective: To investigate mesenteric microcirculatory dysfunctionand its relationship with bacterial translocation (BT) in a rat modelof intestinal obstruction and ischemia (OI).Methods: Anesthetized (pentobarbital 50 mg/kg, ip) male Wistarrats (250-350 g) were submitted to OI (ligature at 1.5 cm proximalto the ileocecal valve, and ligation of mesenteric vessels that supply

7-10 cm of ileal loop) or laparotomy (Sham), and evaluated 24 hoursthereafter. Bacterial translocation was accessed by bacterial cultureof mesenteric lymph nodes, liver, spleen, and blood. Leukocyte-endothelial interactions at the mesenteric microcirculation wereaccessed by intravital microscopy.Results: Rats with OI presented increased numbers of rollingleukocytes (320.9 ± 15.1/10 min), adhered leukocytes (14.0 ± 0.6/100 μm), and migrated cells (11.2 ± 0.4/5000 μm2) vs Sham rats(rollers, 135.9 ± 2.9/10 min; adhered cells, 2.6 ± 0.4/100 μm;migrated cells, 0.5 ± 0.2/5000 μm2; P b .05). About 86% of OI ratspresented positive cultures for E coli in samples of mesentericlymph nodes, liver, and spleen, and 57% had positive hemocultures.In addition, OI rats exhibited decreased PaCO2, alkalosis, hyperlac-tatemia, hyperglycemia, increased blood potassium, hepatic enzymeactivity, serum urea, creatinine, and bilirubin. A high mortality ratewas observed after OI (83%) vs Sham (0%) at 72 hours.Conclusion: Intestinal obstruction and ischemia in rats is a relevantmodel for the in vivo study of mesenteric microcirculatorydysfunction associated with BT and parallels the events implicatedin multiple organ failure and death.

doi:10.1016/j.jcrc.2008.03.025

Immune response to influenza A

Ian Price, David Swigon, Bard Ermentrout, Ted Ross, FranklinToapanta, Gilles ClermontDepartments of Critical Care Medicine and Mathematics,University of Pittsburgh, Pittsburgh, PA 15260

In mammals, influenza A virus first triggers innate immunity and thenadaptive immunity. Yet, an exaggerated response is harmful to tissueand does not aid in eliminating virus. This project seeks to model theimmune response and identify methods of preventing lung failure andimproving recovery. The model expands upon existing models ofadaptive immune response to influenza A virus, adding a dynamicinnate immune response and relevant biological compartments. Theproject uses an equation-based model to study the dynamics ofregulation between virus, immune and respiratory cells, and macro-molecules. The model is calibrated to a greatly expanded data set thatincludes blood, lung and spleen cytokine levels, chemokine levels, cellpopulations, as well as organ function, and survival. Mathematicaltechniques explore solutions to the inverse problem and addressuncertainties and lapses in data in a fully stochastic framework. Themodel, as developed, gives us a metric relating initial infection,immune responses, and total lung damage. Decoding the pathways ofviral immune response allows us to measure the effect on overalldamage and time of recovery of changing multiple pathways, andmotivates experimental study of interventions successful in the model.

doi:10.1016/j.jcrc.2008.03.026

Lipopolysaccharide-caused neurodegenerative diseases

Ines NiehausKiel, Germany

Lipopolysaccharides (LPS or endotoxin) are part of the outer cellwall of Gram-negative bacteria. Lipopolysaccharide-inducedsystemic inflammation triggers sepsis with multiple-organ failureand death in the worst case. Signs of cerebral and sysResearch

270 Abstracts