Mimicry of human sepsis in a rat model--prospects and limitations

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 -