SHOCK AND HEMORRHAGE: AN OVERVIEW OF ANIMAL MODELS

Shock resulting from life-threatening blood loss (hemorrhage) remains a common complication of traumatic injury. Intensive experimental efforts are needed if we are to understand the pathological effect(s) of hemorrhagic shock, alone or in association with traumatic tissue injury, and to reverse this deleterious process in trauma patients. Here, we overview selected studies that are representative of the different hemorrhagic shock models, considering their advantages and disadvantages from a scientific and clinical perspective. Fixed-pressure versus fixed-volume versus uncontrolled hemorrhage models, with or without tissue injury, will be discussed, as well as small versus large animal models. Most of these models are nonlethal in nature, and allow the researcher to understand the changes that contribute to increased susceptibility to subsequent infection or the development of multiple organ failure. We also consider some of the confounders in these models, including anesthesia, the nature of resuscitation, and the use of anticoagulants. The selection of model must take into consideration not only the need for experimental control but must also adequately reflect the clinical pathobiology of shock if we are to develop better pharmacological interventions.

[1]  F. Taylor,et al.  Prolonged shock in the baboon subjected to infusion of E. coli endotoxin. , 1978, Circulatory shock.

[2]  G. Machiedo,et al.  Endotoxemia and Bacteremia During Hemorrhagic Shock The Link Between Trauma and Sepsis? , 1988, Annals of surgery.

[3]  C. Svensen,et al.  Lower Dose of Hypertonic Saline Dextran Reduces the Risk of Lethal Rebleeding in Uncontrolled Hemorrhage , 2002, Shock.

[4]  O. Levang,et al.  The influence of thoracic epidural analgesia alone and in combination with general anesthesia on cardiovascular function and myocardial metabolism in patients receiving beta-adrenergic blockers. , 1993, Anesthesia and analgesia.

[5]  D. Scott,et al.  Vaccines against Campylobacter jejuni. , 1997, The Journal of infectious diseases.

[6]  Arthur S Slutsky,et al.  Effects of albumin and Ringer’s lactate on production of lung cytokines and hydrogen peroxide after resuscitated hemorrhage and endotoxemia in rats , 2003, Critical care medicine.

[7]  Xu Wang,et al.  Multiple resuscitation regimens in a near-fatal porcine aortic injury hemorrhage model. , 1995, Academic Emergency Medicine.

[8]  I. Chaudry,et al.  Immune dysfunction following trauma-haemorrhage: influence of gender and age. , 2000, Cytokine.

[9]  G. Shires,et al.  The effects of varying fluid volume and rate of resuscitation during uncontrolled hemorrhage. , 1999, The Journal of trauma.

[10]  M. Giroud,et al.  Man-in-the-barrel syndrome after hemorrhagic shock. , 2003, The Journal of trauma.

[11]  D. Tweardy,et al.  Activation of STAT proteins in the lung of rats following resuscitation from hemorrhagic shock , 1998, Archives of Orthopaedic and Trauma Surgery.

[12]  A. Crane,et al.  Local Changes in Cerebral Glucose Utilization during Ketamine Anesthesia , 1982, Anesthesiology.

[13]  A. Sauaia,et al.  Postinjury multiple organ failure: a bimodal phenomenon. , 1996, The Journal of trauma.

[14]  C. Wade,et al.  The detrimental effects of intravenous crystalloid after aortotomy in swine. , 1991, Surgery.

[15]  W. Cioffi,et al.  Differential Effects of Macrophage Inflammatory Chemokine-2 and Keratinocyte-Derived Chemokine on Hemorrhage-Induced Neutrophil Priming for Lung Inflammation: Assessment by Adoptive Cells Transfer in Mice , 2003, Shock.

[16]  D. Devereux,et al.  Heparin pretreatment suppresses norepinephrine concentrations in dogs in endotoxic shock. , 1977, Clinical chemistry.

[17]  A. Baue,et al.  Mitochondrial metabolism of succinate, beta-hydroxybutyrate, and alpha-ketoglutarate in hemorrhagic shock. , 1971, The American journal of physiology.

[18]  P. Renshaw,et al.  Metabolic and ionic changes in muscle during hemorrhagic shock. , 1988, Circulatory shock.

[19]  T. Eisenstein,et al.  Morphine induces sepsis in mice. , 1997, The Journal of infectious diseases.

[20]  W. L. Read,et al.  In vivo coagulation; a probable cause of irreversible shock. , 1955, The American journal of physiology.

[21]  A. Peitzman,et al.  Effects of hemodilution on long-term survival in an uncontrolled hemorrhagic shock model in rats. , 1997, The Journal of trauma.

[22]  G. T. Shires,et al.  Cellular transport defects in hemorrhagic shock. , 1971, Surgery.

[23]  M. Rocha e Silva,et al.  Fluid resuscitation improves hemodynamics without increased bleeding in a model of uncontrolled hemorrhage induced by an iliac artery tear in dogs. , 2002, The Journal of trauma.

[24]  V. Pugh,et al.  Preoptic hypothalamic lesions reduce adrenergic vascular compensation during hemorrhagic shock. , 1990, Circulatory shock.

[25]  D. Boggs,et al.  Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice , 1985, American journal of hematology.

[26]  A. Peitzman,et al.  Improved outcome with fluid restriction in treatment of uncontrolled hemorrhagic shock. , 1995, Journal of the American College of Surgeons.

[27]  P. Wang,et al.  Resuscitation after uncontrolled venous hemorrhage: Does increased resuscitation volume improve regional perfusion? , 1998, The Journal of trauma.

[28]  W. Loomis,et al.  Hypertonic saline resuscitation decreases susceptibility to sepsis after hemorrhagic shock. , 1997, The Journal of trauma.

[29]  H. Phelan,et al.  Impact of alcohol intoxication on hemodynamic, metabolic, and cytokine responses to hemorrhagic shock. , 2002, The Journal of trauma.

[30]  J. Vincent Prevention and Therapy of Multiple Organ Failure , 1996, World Journal of Surgery.

[31]  B. Altura DPAVP: a vasopressin analog with selective microvascular and RES actions for the treatment of circulatory shock in rats. , 1976, European journal of pharmacology.

[32]  O. Götze,et al.  Complement Activation During Hemorrhagic Shock and Resuscitation in Swine , 2003, Shock.

[33]  N. Abumrad,et al.  Mammalian opiate alkaloid synthesis: lessons derived from plant biochemistry. , 1999, Shock.

[34]  H. Redl,et al.  Procalcitonin release patterns in a baboon model of trauma and sepsis: Relationship to cytokines and neopterin , 2000, Critical care medicine.

[35]  C. Jacobs,et al.  An assay for the quantitative measurement of in vitro phagocytosis of early apoptotic thymocytes by murine resident peritoneal macrophages. , 1999, Journal of immunological methods.

[36]  I. Chaudry,et al.  Protective effects of preheparinization on the microvasculature during and after hemorrhagic shock. , 1992, The Journal of trauma.

[37]  L. F. Poli de Figueiredo,et al.  Blood loss after fluid resuscitation with isotonic or hypertonic saline for the initial treatment of uncontrolled hemorrhage induced by spleen rupture. , 2003, The Journal of trauma.

[38]  G. Duff,et al.  Interleukin 1: the first interleukin. , 1990, Immunology today.

[39]  P. F. Hill,et al.  A PORCINE MODEL OF SEPSIS RESULTING FROM THE COMBINED INSULTS OF HEMORRHAGE AND PERITONITIS , 2000, Shock.

[40]  W. Mcbride,et al.  An investigation of the effects of heparin, low molecular weight heparin, protamine, and fentanyl on the balance of pro‐ and anti‐inflammatory cytokines in in‐vitro monocyte cultures , 1996, Anaesthesia.

[41]  S. Keller,et al.  Perflubron Emulsion Improves Hepatic Microvascular Integrity and Mitochondrial Redox State After Hemorrhagic Shock , 2003, Shock.

[42]  V. Engelhard,et al.  Demonstration of a calcium influx in cytolytic T lymphocytes in response to target cell binding. , 1987, Journal of immunology.

[43]  I. Chaudry,et al.  Trauma-haemorrhage-induced alterations in thymic prolactin receptor expression: implications in immune dysfunction. , 2002, Cytokine.

[44]  E. Abraham,et al.  Hemorrhage produces abnormalities in lymphocyte function and lymphokine generation. , 1989, Journal of immunology.

[45]  D. Livingston,et al.  Bone marrow failure after hemorrhagic shock. , 1990, Circulatory shock.

[46]  B. Zingarelli,et al.  Amelioration by mercaptoethylguanidine of the vascular and energetic failure in haemorrhagic shock in the anesthetised rat. , 1997, European journal of pharmacology.

[47]  L. Mela,et al.  Defective oxidative metabolism of rat liver mitochondria in hemorrhagic and endotoxin shock. , 1971, The American journal of physiology.

[48]  Collins Ja The pathophysiology of hemorrhagic shock. , 1982 .

[49]  R. Hahn,et al.  Central and regional hemodynamics during crystalloid fluid therapy after uncontrolled intra-abdominal bleeding. , 1998, The Journal of trauma.

[50]  I. Chaudry,et al.  Mechanism of immunosuppression following hemorrhage: defective antigen presentation by macrophages. , 1989, The Journal of surgical research.

[51]  C. H. Baker,et al.  Microvascular responses of intact and adrenal medullectomized rats to hemorrhagic shock. , 1988, Circulatory shock.

[52]  I. Chaudry,et al.  Trauma-induced suppression of antigen presentation and expression of major histocompatibility class II antigen complex in leukocytes. , 1996, Shock.

[53]  P E Pepe,et al.  Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. , 1994, The New England journal of medicine.

[54]  W. Penfield THE TREATMENT OF SEVERE AND PROGRESSIVE HEMORRHAGE BY INTRAVENOUS INJECTIONS , 1919 .

[55]  A. Peitzman,et al.  Essential Role of Induced Nitric Oxide in the Initiation of the Inflammatory Response after Hemorrhagic Shock , 1998, The Journal of experimental medicine.

[56]  A. M. Lefer,et al.  Salutary consequences of blockade of platelet activating factor in hemorrhagic shock. , 1988, European journal of pharmacology.

[57]  K. Tian,et al.  Effect of initial fluid resuscitation on subsequent treatment in uncontrolled hemorrhagic shock in rats. , 2004, Shock.

[58]  I. Chaudry,et al.  Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis. , 2001, Cytokine.

[59]  Cora K. Ogle,et al.  Beneficial effects of aggressive protein feeding in severely burned children. , 1980 .

[60]  J. Marshall,et al.  Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung: role in pulmonary inflammation following lipopolysaccharide. , 1998, Journal of immunology.

[61]  Y. Kamiyama,et al.  Pathophysiology of hemorrhagic shock. II. Anoxic metabolism of the rat liver following acute blood loss in the rat. , 1981, Circulatory shock.

[62]  R. L. Fulton,et al.  The predisposition to infection following hemorrhagic shock. , 1977, Surgery, gynecology & obstetrics.

[63]  G. A. LE PAGE The effects of hemorrhage on tissue metabolites. , 1946, The American journal of physiology.

[64]  M. Devidas,et al.  Production of interleukin-10 in human fracture soft-tissue hematomas. , 1996, Shock.

[65]  D. Tweardy,et al.  Amplification of the proinflammatory transcription factor cascade increases with severity of uncontrolled hemorrhage in swine. , 2003, The Journal of surgical research.

[66]  H. Redl,et al.  Hemorrhagic Shock Induces an S 100 B Increase Associated With Shock Severity , 2003, Shock.

[67]  A. Faden,et al.  Selective cardiorespiratory effects mediated by mu opioid receptors in the nucleus ambiguus , 1984, Neuropharmacology.

[68]  R. Berg,et al.  Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation. , 1988, Surgery.

[69]  W. Schumer Localization of the energy pathway block in shock. , 1968, Surgery.

[70]  M. Todd,et al.  A Comparison of the Cerebrovascular and Metabolic Effects of Halothane and Isolflurane in the Cat , 1984, Anesthesiology.

[71]  H. M. Lazarus,et al.  Effects of hemorrhagic shock on nuclear DNA. , 1979, Surgery.

[72]  C. Wiggers THE PRESENT STATUS OF THE SHOCK PROBLEM , 1942 .

[73]  R. Prielipp,et al.  Total parenteral nutrition increases mortality after hemorrhage , 1991, Critical care medicine.

[74]  M. Healey,et al.  Irreversible shock is not irreversible: a new model of massive hemorrhage and resuscitation. , 2001, The Journal of trauma.

[75]  S. Cheng,et al.  Effects of anesthesia on intermediary metabolism. , 1975, Annual review of medicine.

[76]  I. Chaudry,et al.  Prolonged immunodepression after trauma and hemorrhagic shock. , 1998, The Journal of trauma.

[77]  Joel W. Cohen,et al.  Spending and service use among people with the fifteen most costly medical conditions, 1997. , 2003, Health affairs.

[78]  S. Vogel,et al.  Induction of Early Inflammatory Gene Expression in a Murine Model of Nonresuscitated, Fixed-Volume Hemorrhage , 2002, Shock.

[79]  Jeffrey S. Young,et al.  Improved resuscitation minimizes respiratory dysfunction and blunts interleukin-6 and nuclear factor-&kgr;B activation after traumatic hemorrhage* , 2002, Critical care medicine.

[80]  R. Cowley,et al.  Different response of hepatic energy change and adenine nucleotide concentrations to hemorrhagic shock , 1976, Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie.

[81]  J. Gottlieb,et al.  Gastrointestinal complications in critically ill patients: the intensivists' overview. , 1986, The American journal of gastroenterology.

[82]  J. Marshall,et al.  Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock. , 1998, Journal of immunology.

[83]  T. Billiar,et al.  Neutrophil accumulation and damage to the gastric mucosa in resuscitated hemorrhagic shock is independent of inducible nitric oxide synthase. , 1999, Shock.

[84]  I. Chaudry,et al.  Testosterone and/or low estradiol: normally required but harmful immunologically for males after trauma-hemorrhage. , 1997, The Journal of trauma.

[85]  W. Bickell,et al.  Fluid replacement for hypotensive injury victims: how, when and what risks? , 1998, Current opinion in anaesthesiology.

[86]  B. Altura Microcirculatory approach to the treatment of circulatory shock with a new analog of vasopressin, (2-phenylalanine, 8-ornithine)vasopressin. , 1976, The Journal of pharmacology and experimental therapeutics.

[87]  G. Shires,et al.  Liver cell membrane alterations during hemorrhagic shock in the rat. , 1981, The Journal of surgical research.

[88]  R. S. Rhodes,et al.  Mitochondrial dysfunction of the liver and hypoglycemia in hemorrhagic shock. , 1980, Surgery, gynecology & obstetrics.

[89]  P. Molina,et al.  Hemorrhage alters neuroendocrine, hemodynamic, and compartment-specific TNF responses to LPS. , 2001, Shock.

[90]  E. Arias,et al.  Deaths: final data for 2001. , 2003, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[91]  M. L. Bay,et al.  Effects of sevoflurane general anesthesia: immunological studies in mice. , 2002, International immunopharmacology.

[92]  Z. Ba,et al.  Trauma-hemorrhage and resuscitation in the mouse: effects on cardiac output and organ blood flow. , 1993, The American journal of physiology.

[93]  A. Pope,et al.  Fluid Resuscitation: State of the Science for Treating Combat Casualties and Civilian Injuries , 1999 .

[94]  J. Collins,et al.  The effects of the concentration and function of hemoglobin on the survival of rats after hemorrhage. , 1979, Surgery.

[95]  J. Russell,et al.  BIOCHEMICAL STUDIES ON SHOCK : II. THE ROLE OF THE PERIPHERAL TISSUES IN THE METABOLISM OF PROTEIN AND CARBOHYDRATE DURING HEMORRHAGIC SHOCK IN THE RAT. , 1944 .

[96]  I. Chaudry,et al.  Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage. , 1997, The American journal of physiology.

[97]  M. Krausz,et al.  Improved Survival in Uncontrolled Hemorrhagic Shock Induced by Massive Splenic Injury in the Proestrus Phase of the Reproductive Cycle in the Female Rat , 2003, Shock.

[98]  Z. Żukowska-Grójec,et al.  Effect of pentobarbital anesthesia on the pressor response to agonists in vivo in normal and endotoxemic rats. , 1995, Research Communications in Molecular Pathology and Pharmacology.

[99]  I. Chaudry,et al.  Defective macrophage antigen presentation following haemorrhage is associated with the loss of MHC class II (Ia) antigens. , 1990, Immunology.

[100]  B. Zweifach,et al.  Beneficial action of pretreatment with chlorpromazine on survival following graded hemorrhage in the rat. , 1955, Surgery, gynecology & obstetrics.

[101]  D. Remick,et al.  Low molecular weight heparin is associated with greater cytokine production in a stimulated whole blood model. , 1998, Shock.

[102]  P. W. Willis,et al.  Some side effects of heparin, heparinoids, and their antagonists , 1966, Clinical pharmacology and therapeutics.

[103]  E. Abraham,et al.  Effects of hemorrhage on interleukin-1 production. , 1988, Circulatory shock.

[104]  L. Ga The effects of hemorrhage on tissue metabolites. , 1946 .

[105]  E. Deitch,et al.  Gut injury and gut-induced lung injury after trauma hemorrhagic shock is gender and estrus cycle specific in the rat. , 2003, The Journal of trauma.

[106]  W. Cioffi,et al.  Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. , 2002, The American journal of pathology.

[107]  I. Chaudry,et al.  Differences in the expression of LPS-receptors are not responsible for the sex-specific immune response after trauma and hemorrhagic shock. , 2004, Cellular immunology.

[108]  E. Deitch,et al.  Sex hormones modulate distant organ injury in both a trauma/hemorrhagic shock model and a burn model. , 2005, Surgery.

[109]  D. Prough,et al.  Near-infrared spectroscopy-guided closed-loop resuscitation of hemorrhage. , 2003, The Journal of trauma.

[110]  P. Pelosi,et al.  Resuscitation from hemorrhagic shock: Experimental model comparing normal saline, dextran, and hypertonic saline solutions , 2003, Critical care medicine.

[111]  P. Rhee,et al.  Ketone and pyruvate Ringer's solutions decrease pulmonary apoptosis in a rat model of severe hemorrhagic shock and resuscitation. , 2003, Surgery.

[112]  J. Alexander,et al.  Beneficial Effects of Aggressive Protein Feeding in Severely Burned Children , 1980, Annals of surgery.

[113]  M. Krausz,et al.  Bolus versus continuous fluid resuscitation and splenectomy for treatment of uncontrolled hemorrhagic shock after massive splenic injury. , 2003, The Journal of trauma.

[114]  H. L. Stone,et al.  Cardiovascular effects of halothane, methoxyflurane, pentobarbital, and thiamylal. , 1971, Journal of applied physiology.

[115]  R. Bandler,et al.  Haemodynamic response to haemorrhage: distinct contributions of midbrain and forebrain structures , 2003, Autonomic Neuroscience.

[116]  M H Weil,et al.  Experimental and Clinical Studies on Lactate and Pyruvate as Indicators of the Severity of Acute Circulatory Failure (Shock) , 1970, Circulation.

[117]  T. Scalea,et al.  Detrimental Effects of Rapid Fluid Resuscitation on Hepatocellular Function and Survival After Hemorrhagic Shock , 2002, Shock.