MATHEMATICAL MODELING OF POSTHEMORRHAGE INFLAMMATION IN MICE: STUDIES USING A NOVEL, COMPUTER-CONTROLLED, CLOSED-LOOP HEMORRHAGE APPARATUS.
Torres, Andres *; Bentley, Timothy +; Bartels, John ++; Sarkar, Joydeep ++; Barclay, Derek *; Namas, Rajaie *; Constantine, Gregory [S]; Zamora, Ruben *; Puyana, Juan Carlos *[//][P]; Vodovotz, Yoram [//]*
32(2):172-178, August 2009.
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Hemorrhagic shock (HS) elicits a global acute inflammatory response, organ dysfunction, and death. We have used mathematical modeling of inflammation and tissue damage/dysfunction to gain insight into this complex response in mice. We sought to increase the fidelity of our mathematical model and to establish a platform for testing predictions of this model. Accordingly, we constructed a computerized, closed-loop system for mouse HS. The intensity, duration, and time to achieve target MAP could all be controlled using a software. Fifty-four male C57/black mice either were untreated or underwent surgical cannulation. The cannulated mice were divided into 8 groups: (a) 1, 2, 3, or 4 h of surgical cannulation alone and b) 1, 2, 3, or 4 h of cannulation HS (25 mmHg). MAP was sustained by the computer-controlled reinfusion and withdrawal of shed blood within /-2 mmHg. Plasma was assayed for the cytokines TNF, IL-6, and IL-10 as well as the NO reaction products NO2-/NO3-. The cytokine and NO2-/NO3- data were compared with predictions from a mathematical model of post-hemorrhage inflammation, which was calibrated on different data. To varying degrees, the levels of TNF, IL-6, IL-10, and NO2-/NO3- predicted by the mathematical model matched these data closely. In conclusion, we have established a hardware/software platform that allows for highly accurate, reproducible, and mathematically predictable HS in mice.
(C)2009The Shock Society