Advertisement
Research Article| Volume 29, ISSUE 2, P189-201, August 1980

Download started.

Ok

Sepsis and septic shock—A review of laboratory models and a proposal

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Study of the pathophysiology of infection requires the use of animal models in order to separate the many variables. Meaningful controlled studies of septic patients are difficult because of the diversity of diseases, different organisms, and multiplicity of variables encountered in the clinical setting. Endotoxin animal models, although reproducible, do not adequately simulate many of the circulatory and metabolic alterations produced by sepsis. Numerous sepsis models utilizing bacterial infection have been developed without any standardization of approach and there are often problems of reproducibility. When we began to study sepsis, we found that many of the proposed and reported small animal models of sepsis could not be reproduced in our laboratory. This led us through a long period of trial and error in order to develop a reproducible and satisfactory small animal sepsis model. Because of this, and the need for review and standardization, previously used models of sepsis such as the administration of endotoxin, intravenous infusion of live organisms, the administration of fecal material into the peritoneal cavity, the placement of infected foreign material into the soft tissues of the extremity, and surgical operations that partially destroy the normal barriers of the gastrointestinal tract are reviewed. Modifications of an existing sepsis model in the rat are also presented, and criteria for future models for the study of sepsis such as reproducibility of the model, clinical signs of sepsis, positive blood cultures, and alterations of vital signs are proposed.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Archer L.T.
        Hypoglycemia in conscious dogs in liver E. coli septicemia: A chronic study.
        Circ. Shock. 1976; 3: 93
        • Bartlett J.G.
        • Onderdonk A.B.
        • Louie T.
        • et al.
        Lessons from an animal model of intra-abdominal sepsis.
        Arch. Surg. 1978; 113: 853
        • Baue A.E.
        Recent developments in the study and treatment of shock.
        Surg. Gynecol. Obstet. 1968; 127: 849
        • Baue A.E.
        The treatment of septic shock: A problem intensified by advancing science.
        Surgery. 1969; 65: 850
        • Baue A.E.
        Multiple, progressive or sequential systems failure.
        in: A syndrome of the 1970's. 3rd ed. Arch. Surg.110. 1975: 779
        • Beeson P.B.
        • McDermott W.
        3rd ed. Textbook of Medicine. Saunders, Philadelphia1975: 904
        • Blakiston
        3rd ed. Blakiston's Gould Medical Dictionary. McGraw-Hill, New York1972
        • Boivin A.
        Bacteries et Virus.
        Presses Universitaires de France, Paris1941
        • Borden C.W.
        • Hall W.H.
        Fatal transfusion reactions from massive bacterial contamination of blood.
        N. Engl. J. Med. 1951; 245: 760
        • Braude A.E.
        • Siemienski J.
        • Williams D.
        • Sanford J.P.
        Overwhelming bacteremic shock produced by gram-negative bacilli: A report of four cases with one recovery.
        Univ. Mich. Med. Bull. 1953; 19: 23
        • Browne M.K.
        • Leslie G.B.
        Animal models of peritonitis.
        Surg. Gynecol. Obstet. 1976; 143: 738
        • Chaudry I.H.
        • Wichterman K.A.
        • Baue A.E.
        Effect of sepsis on tissue adenine nucleotide levels.
        Surgery. 1979; 85: 205
        • Chaudry I.H.
        • Hirasawa H.
        • Baue A.E.
        Impairment of reticuloendothelial system function with sepsis and its improvement with ATP-MgCl2 and glucose administration.
        in: Schumer W. Spitzer J.J. Marshall B.E. 5th ed. Advances in Shock Research. Vol. 2. Liss, New York1979: 153
        • Clowes G.H.A.
        • Zuschneid W.
        • Turner M.
        • et al.
        Observations on the pathogenesis of the pneumonitis associated with severe infection in other parts of the body.
        Ann. Surg. 1968; 167: 630
        • Clowes G.H.A.
        • O'Donnell T.F.
        • Blackburn G.L.
        • et al.
        Energy metabolism and proteolysis in traumatized and septic man.
        Surg. Clin. North Amer. 1976; 56: 1169
        • Cowie D.M.
        • Calhoun H.
        Non-septic therapy in arthritis and infections.
        Arch. Intern. Med. 1919; 23: 69
        • Cryer P.E.
        • Herman C.M.
        • Sode J.
        Carbohydrate metabolism in the baboon subjected to gram-negative (E. Coli) septicemia.
        Ann. Surg. 1971; 174: 91
        • Decker G.A.G.
        • Daniel A.M.
        • Blevings S.
        • Maclean L.D.
        Effect of peritonitis on mitochondrial respiration.
        J. Surg. Res. 1971; 11: 528
        • Eiseman B.
        • Bogart R.
        • Norton K.
        Multiple organ failure.
        Surg. Gynecol. Obstet. 1977; 144: 323
        • Filkins J.P.
        • Cornell R.P.
        Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxin shock.
        Amer. J. Physiol. 1974; 227: 778
        • Fischer R.P.
        • Polk H.C.
        Changing etiologic patterns of renal insufficiency in surgical patients.
        Surg. Gynecol. Obstet. 1975; 140: 85
        • Greenfield L.J.
        • Jackson R.H.
        • Elkins R.C.
        • et al.
        Cardiopulmonary effects of volume loading in primates in endotoxin shock.
        Surgery. 1974; 76: 560
        • Greisman S.E.
        • Hornick R.B.
        • Wagner Jr., H.N.
        • et al.
        The role of endotoxin during typhoid fever and tularemia in man-IV. The integrity of the endotoxin tolerance mechanism during infection.
        J. Clin. Invest. 1969; 48: 613
        • Gump F.E.
        • Long C.
        • Killian P.
        • et al.
        Studies of glucose intolerance in septic injured patients.
        J. Trauma. 1974; 14: 378
        • Gump F.E.
        • Long C.L.
        • Gieger J.W.
        • et al.
        The significance of altered gluconeogenesis in surgical catabolism.
        J. Trauma. 1976; 15: 193
        • Hau T.
        • Simmons R.L.
        Surgical pros and cons.
        Surg. Gynecol. Obstet. 1977; 144: 755
        • Hermreck A.S.
        • Berg R.A.
        • Ruhlen J.R.
        • MacArthur R.I.
        Renal response to sepsis.
        Arch. Surg. 1973; 197: 1969
        • Hermreck A.S.
        • Thai A.P.
        Mechanisms for the high circulatory requirements in sepsis and septic shock.
        Ann. Surg. 1969; 170: 677
        • Hinshaw L.B.
        Concise review—The role of glucose in endotoxin shock.
        Circ. Shock. 1976; 3: 1
        • Hirasawa H.
        • Chaudry I.H.
        • Baue A.E.
        Beneficial effect of ATP-MgCl2-glucose administration on survival following sepsis.
        Surg. Forum. 1978; 29: 11
        • Holtzman S.
        • Schuler J.J.
        • Earnest W.
        Carbohydrate metabolism in endotoxemia.
        Circ. Shock. 1974; 1: 99
        • Imamura M.
        • Clowes G.H.A.
        Hepatic blood flow and oxygen consumption in starvation and septic shock.
        Surg. Gynecol. Obstet. 1975; 141: 27
        • LaNoue K.F.
        • Mason A.D.
        • Daniels J.P.
        The impairment of gluconeogenesis by gramnegative infection.
        Metabolism. 1968; 17: 606
        • Long C.L.
        • Kinney J.M.
        • Geiger J.W.
        Nonsuppressability of gluconeogenesis by glucose in septic patients.
        Metabolism. 1976; 25: 193
        • MacLean L.D.
        • Mulligan W.G.
        • McLean A.P.H.
        • et al.
        Patterns of septic shock in man—A detailed study of 56 patients.
        Ann. Surg. 1967; 160: 543
        • MacNicol M.F.
        • Clowes G.H.A.
        Comparison of proteolysis induced by starvation, sepsis and infusion of bradykinen or endotoxin.
        Surg. Forum. 1972; 25: 45
        • Martinez G.L.A.
        • Quintiliani R.
        • Tilton R.C.
        Clinical experience on the detection of endotoxemia with the limulus test.
        J. Infect. Dis. 1973; 127: 102
        • McGill M.W.
        • Porter P.J.
        • Kass E.H.
        The use of bioassay for endotoxin in clinical infections.
        J. Infect Dis. 1970; 121: 103
        • McCabe W.R.
        Gram-negative bacteremia.
        Adv. Intern. Med. 1974; 19: 135
        • Morgan H.R.
        Preparation of antigenic material inducing leucopenia from Eberthella typhosa in a synthetic medium.
        in: 5th ed. Proc. Soc. Exp. Biol. Med.43. 1949: 529
        • O'Donnell T.F.
        • Clowes G.H.A.
        • Ryan N.T.
        • et al.
        Experimental endotoxemia: Does it stimulate metabolism in septic shock.
        Surg. Forum. 1957; 26: 25
        • Onderdonk A.B.
        • Weinstein W.M.
        • Sullivan N.M.
        • et al.
        Experimental intraabdominal abscesses in rats: Quantitative bacteriology of infected animals.
        Infect. Immun. 1974; 10: 1256
        • Onderdonk A.B.
        • Bartlett J.G.
        • Louis T.
        • et al.
        Microbial synergy in experimental intra-abdominal abscess.
        Infect. Immun. 1976; 13: 22
        • Pappova E.
        • Urbascheck B.
        • Heitmann L.
        • et al.
        Energy-rich phosphate and glucose metabolism in early endotoxin shock.
        J. Surg. Res. 1971; 11: 506
        • Perbellini A.
        • Shatney C.H.
        • DacCarter D.J.
        • Lillehi R.C.
        A new model for the study of septic shock.
        Surg. Gynecol. Obstet. 1978; 147: 68
        • Perkash I.
        • Satpati P.
        • Agawal K.C.
        • et al.
        Prolonged peritoneal lavage and fecal peritonitis.
        Surgery. 1970; 58: 842
        • Pitcarin M.
        • Schuler J.
        • Erve P.R.
        • et al.
        Glucocorticoid and antibiotic effect on experimental gram-negative bacteremic shock.
        Arch. Surg. 1975; 110: 1012
        • Polk H.C.
        • Shields C.L.
        Remote organ failure: A valid sign of occult intra-abdominal infection.
        Surgery. 1977; 81: 310
        • Postel J.
        • Schloerb P.R.
        • Furtado D.
        Pathophysiologic alterations during bacterial infusions for the study of bacteremic shock.
        Surg. Gynecol. Obstet. 1975; 141: 683
        • Postel J.
        • Schloerb P.R.
        Metabolic effects of experimental bacteremia.
        Ann. Surg. 1977; 185: 475
        • Robertson R.C.
        • Yu H.
        Leukopenia and the toxic substances of B. typhosus.
        J. Hyg. (Camb.). 1938; 38: 299
        • Ryan N.T.
        • Blackburn G.L.
        • Clowes G.H.A.
        Differential tissue sensitivity to elevated endogenous insulin levels during experimental peritonitis in rats.
        Metabolism. 1974; 23: 1081
        • Sleeman H.K.
        • Diggs J.W.
        • Hayes D.K.
        • Hamit H.F.
        Values of antibiotics, corticosteroids and peritoneal lavage in the treatment of experimental peritonitis.
        Surgery. 1969; 66: 1960
        • Stumacher R.J.
        • Kovnat M.J.
        • McCabe W.R.
        Limitation of the usefulness of the limulus assay for endotoxin.
        N. Engl. J. Med. 1973; 288: 1261
        • Swan K.G.
        • Jacobson E.D.
        Hemodynamics of endotoxin shock in the conscious animal.
        Surg. Gynecol. Obstet. 1967; 125: 1041
        • Swan K.G.
        • Reynolds D.G.
        Blood flow to the liver and spleen during endotoxin shock in the baboon.
        Surgery. 1972; 72: 388
        • Thal A.P.
        • Robinson R.G.
        • Pruett R.
        • et al.
        The critical relationship in intravascular blood volume and vascular capacitance in sepsis.
        Surg. Gynecol. Obstet. 1976; 143: 17
        • Thal A.P.
        5th ed. Rhoad's Textbook of Surgery—Principles and Practice. Lippincott, Philadelphia/Toronto1977: 84
        • Waisbren B.A.
        Gram-negative shock and endotoxin shock.
        Amer. J. Med. 1964; 36: 819
        • Walker H.L.
        • Mason A.D.
        • Raulston G.L.
        Surface infection with Pseudomonas aeruginosa.
        Ann. Surg. 1964; 160: 297
        • Wichterman K.A.
        • Chaudry I.H.
        • Baue A.E.
        Studies of peripheral glucose uptake during sepsis.
        Arch. Surg. 1979; 114: 740
        • Weinstein W.M.
        • Onderdonk A.B.
        • Bartlett J.G.
        • et al.
        Experimental intra-abdominal abscesses in rats: Development of an experimental model.
        Infect. Immun. 1974; 10: 1250
        • Willerson J.T.
        • Trelstad R.L.
        • Pincus T.
        • et al.
        Subcellular localization of Salmonella enteridis endotoxin in liver and spleen of mice and rats.
        Infect. Immun. 1970; 1: 440
        • Wolff S.M.
        • Bennett J.V.
        Gram-negative-rod bacteremia.
        N. Engl. J. Med. 1974; 291: 733
        • Wright C.J.
        • Duff H.J.
        • MacLean A.P.H.
        • et al.
        Regional capillary blood flow and oxygen uptake in severe sepsis.
        Surg. Gynecol. Obstet. 1971; 132: 637