Abstract
Sepsis, life-threatening organ dysfunction due to a dysregulated host response to infection, is positively correlated with platelet activation. Furthermore, clinical studies have also shown that platelet activation is associated with sepsis severity, suggesting a role for platelets in sepsis pathophysiology. Despite this correlation, the underlying mechanisms by which activated platelets contribute to sepsis are under investigated. In preliminary studies, we set out to determine if platelet activation is associated with multi-organ dysfunction and injury in a rat model of chronic polymicrobial abdominal sepsis. Sepsis was induced via cecal ligation and puncture (CLP) followed by cecum removal 24 hours post-CLP. At 72 hours post-CLP, blood, urine, and tissues were collected for analysis. Platelet activation was measured via flow cytometry. Lung wet/dry ratio and plasma creatinine were measured to assess lung edema and renal injury, respectively. Platelet activation doubled in CLP rats versus Sham rats. Activated platelets increased from 3.8±1.7% of the gated population in Sham animals (n=5) to 9.2±1.9% of the gated population in CLP animals (n=5; p=0.07). Lung wet/dry ratio significantly increased from 3.9±0.2 in Sham (n=8) to 6.7±1 in CLP rats (n=8; p<0.05). Furthermore, plasma creatinine increased by 33% from 0.55±0.3 mg/dL in Sham animals (n=6) to 0.73±0.06 mg/dL in CLP rats (n=8; p<0.05), indicating a decrease in renal function. These data demonstrate, for the first time, an increase in platelet activation in response to CLP, and identifies an association of activated platelets with pulmonary edema and reduced renal function in the cecal ligation and puncture rat model of abdominal polymicrobial sepsis. Future studies will investigate the underlying mechanisms by which activated platelets contribute to multi-organ dysfunction and injury in sepsis.
Published Version
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