title: Mathematical modeling of posthemorrhage inflammation in mice: studies using a novel, computer-controlled, closed-loop hemorrhage apparatus.
abstract: 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.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Torres
authors.forename: Timothy
authors.initials: T
authors.lastname: Bentley
authors.forename: John
authors.initials: J
authors.lastname: Bartels
authors.forename: Joydeep
authors.initials: J
authors.lastname: Sarkar
authors.forename: Derek
authors.initials: D
authors.lastname: Barclay
authors.forename: Rajaie
authors.initials: R
authors.lastname: Namas
authors.forename: Gregory
authors.initials: G
authors.lastname: Constantine
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Puyana
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D006470:Hemorrhage / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008954:Models, Biological; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D012984:Software
chemical_list: D016207:Cytokines; D009569:Nitric Oxide