Abstract
Objective: To perform a reproducible long-term (10 days) large animal model of multiple systems organ failure without necessity of a continuous stimulus.
Design: Adult female merino sheep submitted to a 5-day stimulation period followed by a 5-day observation period. Day 1: Hemorrhagic shock was combined with a traumatic surgical insult (reamed intra-medullary femoral nailing), followed by serial administrations every 12 h for 5 days of a combination of endotoxin and zymosan activated plasma. Organ function was followed for 5 further days.
Results: Cardiac index increased significantly during the study (day 1: 491 ± 8 mmHg; day 10: 427 ± 20, p<0.05). Liver function was impaired and bilirubin levels increased significantly (day 1: 2.9 ± 0.3 µmol/1; day 10: 7.2 ± 0.9; p<0.05). Creatinine clearance decreased initially (day 1: 54 ± 7 ml/min), increased to a peak on day 2 (104 ± 27), and then deteriorated again (day 10: 53 ± 18).
Conclusion: This new large animal model of trauma-induced MOF is reproducible and may be suitable for the study of new therapeutic approaches to therapy.
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References
Baue AE (1975) Multiple, progressive, or sequential system failure: a syndrome for the 1970s. Arch Surg 110:779–788
Knaus WA, Wagner DP (1989) Multiple systems organ failure: epidemiology and prognosis. Crit Care Clin 5: 221–232
Chaudry IH, Wang P, Singh G, Hauptman JG, Ayla A (1993) Rat and mouse models of hypovolemic-traumatic shock. In: G Schlag, H Redl H (eds) Pathophysiology of shock, sepsis and organ failure. Springer, Berlin, New York, London, pp 371–392
Goris RJA, Boekholtz WKF, Van Bebber IPT, Nuytinck JKS, Schillings PHM (1986) Multiple organ failure and sepsis without bacteria. Arch Surg 121: 897–903
Pape H-C, Dwenger A, Regel G, Schweitzer G, Remmers D, Pape D, Sturm JA (1994) Pulmonary damage after recurrent administration of endotoxin and zymosan activated plasma — a sheep model. Theor Surg 9: 82–89
Pape H-C, Dwenger A, Regel G, Schweitzer G, Remmers D, Pape D, Sturm JA (1993) Hemorrhagic shock, endotoxin and complement activation induce late organ failure in sheep. Theor Surg 8: 21–28
Schlag G, Redl H, Davies J, Van Vuuren CCJ, Smuts P (1993) Live Escherichia coli sepsis models in Baboons. In: Schlag G, Redl H, (eds) Pathophysiology of shock, sepsis and organ failure. Springer Berlin, Heidelberg, New York, pp 1093–1107
Steinberg S, Flynn W, Kelley K, Sharma P, Hassett J, Price R, Flint L (1989) Development of a bacteria-independant model of the multiple organ failure syndrome. Arch Surg 124:1390–1394
Bickhardt K (1987) Organ distribution pattern and plasma half-life times of diagnostically important enzymes in the sheep. Berl Munch Tierärztl Wochenschr 100:155–161
Kox W, Schindler HG, Brug E (1979) Biochemische und histologische Veränderungen nach Trauma und Schock — tierexperimentelle Untersuchungen zur Pathogenese des akuten Lungenversagens und der sogenannten Fettembolie. Hefte Unfallheilkunde 138: 272–275
Rana MW, Sing G, Wang P (1992) Protective effects of preheparinzation on microvasculature during and following hemorrhagic shock. J Trauma 32: 420–425
Pretorius JP, Schlag G, Redl H (1987) The ‘lung in shock’ as a result of hypovolemic-traumatic shock. J Trauma 27: 1344–1352
Pape H-C, Regel G, Dwenger A, Sturm JA (1990) Does additional lung injury and hemorrhagic shock aggravate lung damage from intrameduallary nailing in sheep? Circ Shock 31: 54
Demling RH, Lalonde CC, Jin LJ, Albes J, Fiori N (1986) The pulmonary and systemic response to recurrent endotoxemia in the adult sheep. Surgery 100:876–883
Lang CH, Spitzer JA (1987) Glucose kinetics and development of endotoxin tolerance during long-term endotoxin infusion. Metabolism 36: 469–474
Egan TM, Saunders NR, Luk SC, Cooper JD (1988) Complement mediated pulmonary edema in sheep. J Surg Res 45: 204–214
Doerschuk CM, Allard MF, Hogg JC (1989) Neutrophil kinetics in rabbits during infusion of zymosan activated plasma. J Appl Physiol 67: 88–95
Nuytinck JK, Goris RJ, Weerts JGE, Schillings PHM, Schurmanns JH (1986) Acute generalized microvascular injury by activated complement and hypoxia: the basis of the adult respiratory distress syndrome and multiple organ failure? Br J Exp Pathol 67: 548–553
Deitch EA, Berg RD (1987) Endotoxin but not malnutrition promotes bacterial translocation of the gut flora in burned mice. J Trauma 27, 2:161–166
Regel G, Nerlich ML, Dwenger A, Sturm JA (1989) Induction of pulmonary injury by PMNL after bone marrow fat injection and endotoxemia: a sheep model. Theor Surg 4: 22–30
Pape H-C, Dwenger A, Regel G, Schweitzer G, Jonas M, Remmers D, Krumm K, Sturm JA, Tscherne H (1992) Pulmonary damage after intra-medullary femoral nailing in traumatized sheep — is there any effect of different nailing methods? J Trauma 33: 574–578
Pape H-C, Regel G, Tscherne H (1996) Local and systemic effects of fat embolization after intramedullary reaming and its influence by cofactors. Techniques in Orthop 11,1: 2-13
Pape H-C, Auf m’Kolck M, Paffrath T, Regel G, Sturm JA, Tscherne H (1993) Primary intramedullary femur fixation in multiple trauma patients with associated lung contusion — a cause of post-traumatic ARDS? J Trauma 34, 4: 540–548
Heideman M, Kaiser B, Gelin LE (1978) Complement activation by homogenized muscle tissue. J Surg Res 25: 518–523
Zilow G, Sturm JA, Rother U, Kirsch-fink M (1990) Complement activation and the prognostic value of C3a in patients at risk of adult respiratory distress syndrome. Clin Exp Immun 79:151–155
Deitch EA, Ma WJ, Ma L (1989) Endotoxin-induced bacterial translocation: a study of mechanisms. Surgery 106: 300–302
Pape H-C, Regel G, Dwenger A, Schweitzer G, Krettek K, Sturm JA, Tscherne H (1993) Influences of different methods of intramedullary femoral nailing on lung function in patients with multiple trauma. J Trauma 35, 5: 709-715
Pape H-C, Dwenger A, Grotz M, Kaever V, Negatsch R, Kleemann W, Sturm JA, Tscherne H (1994) Does the reamer type influence the degree of lung dysfunction after femoral nailing following severe trauma? An animal study. J Orthop Trauma 8, 4: 300-309
Wichterman KA, Baue AE, Chaudry IH (1980) Sepsis and septic shock — a review of laboratory models and a proposal. J Surg Res 29:189–201
Goris RJ, Boeckhorst PA, Nuytinck KS (1985) Multiple organ failure: generalized autodestructive inflammation. Arch Surg 20:1109–1120
Pape H-C, Remmers D, Kleemann W, Goris RJA, Tscherne H (1994) Post-traumatic multiple organ failure — a report on clinical and autopsy findings. Shock 1: 228–234
Pape H-C, Dwenger A, Regel G, Goollub F, Wisner D, Sturm JA, Tscherne H (1994) Increased gut permeability after multiple trauma. Br J Surg 81: 850–852
Chaudry IH, Blasko KA, Wagner PA (1989) A clinically relevant model of hemorrhagic shock and resuscitation in the rat. Circ Shock 27: 318–319
Dwenger A, Remmers D, Grotz M, Pape H-C, Gruner A, Jochum M, Regel G (1996) Aprotinin prevents the development of trauma induced MOF in a chronic sheep model. Eur J Clin Chem Clin Biochem 34, 3: 207-214
Remmers D, Dwenger A, Grotz M, Pape H-C, Gruner A, Regel G (1996) Attenuation of multiple organ dysfunction in a chronic sheep model by the 21-aminosteroid U74389 G. J Surg Res 62,2: 278-273
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Supported by “Deutsche Forschungsge-meinschaft”, Proj. No. Re 1015/1-1 and /1-2
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Pape, H.C., Grotz, M., Remmers, D. et al. Multiple organ failure (MOF) after severe trauma — A sheep model. Intensive Care Med 24, 590–598 (1998). https://doi.org/10.1007/s001340050620
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DOI: https://doi.org/10.1007/s001340050620