Mimicry of human sepsis in a rat model--prospects and limitations
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Mimicry of human sepsis in a rat model--prospects and limitations. / Stahl, Oliver; Löffler, Bettina; Haier, Joerg; Mardin, Wolf Arif; Mees, Soeren Torge.
In: J SURG RES, Vol. 179, No. 1, 01.2013, p. e167-75.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Mimicry of human sepsis in a rat model--prospects and limitations
AU - Stahl, Oliver
AU - Löffler, Bettina
AU - Haier, Joerg
AU - Mardin, Wolf Arif
AU - Mees, Soeren Torge
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/1
Y1 - 2013/1
N2 - BACKGROUND: Sepsis and systemic inflammatory response syndrome (SIRS) continue to represent critical conditions with persistently high mortality and continue to need experimental and clinical research. We developed a rat model of gram-positive and gram-negative SIRS/sepsis with in vivo visualization of the pulmonary microcirculation to evaluate the optimal dosage and application path for SIRS/sepsis-inducing agents.METHODS: Male Sprague-Dawley rats (n = 8 per group) were assigned to control, lipopolysaccharide (LPS), alphatoxin, or living Staphylococcus aureus (strain 68/50) groups. SIRS/sepsis was induced by intraperitoneal injection of the differing agents. The onset of SIRS was determined through human sepsis parameters and fluorescence video microscopy-based measurement of platelet and leukocyte velocity within the pulmonary vascular system (injection of 5 × 10(6) calcein AM-labeled nonactivated platelets; leukocytes labeled in vivo by rhodamine).RESULTS: The optimal dosage to induce SIRS was 30 mg/250 g body weight for LPS (bolus injection) and 60 μg/250 g body weight for alphatoxin (2 h continuous perfusion). Sepsis was not achieved by injection of living S. aureus. The onset of SIRS was seen after 2-5 h for LPS and after 2-4 h for alphatoxin after intraperitoneal administration with a significantly increased heart rate, breathing rate, and body temperature (P < 0.05) and significantly decreased cell velocity (P < 0.05).CONCLUSION: Our study represents an effective approach for a gram-negative (LPS) and gram-positive (alphatoxin) SIRS model to mimic human sepsis. Human sepsis-based criteria were used to define SIRS in our rats to achieve an optimal analogy for the human system. In our model, higher dosages were needed for SIRS induction than have been previously reported. The resulting, considerable heterogeneity of current SIRS-inducing models suggests that additional studies in this field are required to define standard procedures.
AB - BACKGROUND: Sepsis and systemic inflammatory response syndrome (SIRS) continue to represent critical conditions with persistently high mortality and continue to need experimental and clinical research. We developed a rat model of gram-positive and gram-negative SIRS/sepsis with in vivo visualization of the pulmonary microcirculation to evaluate the optimal dosage and application path for SIRS/sepsis-inducing agents.METHODS: Male Sprague-Dawley rats (n = 8 per group) were assigned to control, lipopolysaccharide (LPS), alphatoxin, or living Staphylococcus aureus (strain 68/50) groups. SIRS/sepsis was induced by intraperitoneal injection of the differing agents. The onset of SIRS was determined through human sepsis parameters and fluorescence video microscopy-based measurement of platelet and leukocyte velocity within the pulmonary vascular system (injection of 5 × 10(6) calcein AM-labeled nonactivated platelets; leukocytes labeled in vivo by rhodamine).RESULTS: The optimal dosage to induce SIRS was 30 mg/250 g body weight for LPS (bolus injection) and 60 μg/250 g body weight for alphatoxin (2 h continuous perfusion). Sepsis was not achieved by injection of living S. aureus. The onset of SIRS was seen after 2-5 h for LPS and after 2-4 h for alphatoxin after intraperitoneal administration with a significantly increased heart rate, breathing rate, and body temperature (P < 0.05) and significantly decreased cell velocity (P < 0.05).CONCLUSION: Our study represents an effective approach for a gram-negative (LPS) and gram-positive (alphatoxin) SIRS model to mimic human sepsis. Human sepsis-based criteria were used to define SIRS in our rats to achieve an optimal analogy for the human system. In our model, higher dosages were needed for SIRS induction than have been previously reported. The resulting, considerable heterogeneity of current SIRS-inducing models suggests that additional studies in this field are required to define standard procedures.
KW - Animals
KW - Bacterial Toxins
KW - Disease Models, Animal
KW - Hemodynamics
KW - Hemolysin Proteins
KW - Humans
KW - Injections, Intraperitoneal
KW - Lipopolysaccharides
KW - Lung
KW - Male
KW - Microcirculation
KW - Microscopy, Video
KW - Rats
KW - Rats, Sprague-Dawley
KW - Respiration
KW - Sepsis
KW - Systemic Inflammatory Response Syndrome
U2 - 10.1016/j.jss.2012.01.042
DO - 10.1016/j.jss.2012.01.042
M3 - SCORING: Journal article
C2 - 22482762
VL - 179
SP - e167-75
JO - J SURG RES
JF - J SURG RES
SN - 0022-4804
IS - 1
ER -