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Complement activation in peritonitis. Association with hepatic and renal perfusion abnormalities. First place winner:
W J Schirmer1, J M Schirmer, G B Naff
1Department of Surgery, Veterans' Administration Medical Center, Cleveland, Ohio 44106.
Insights
Sepsis triggers complement system activation, leading to reduced liver and kidney blood flow in mice. This study links complement activation to impaired visceral perfusion during sepsis.
Area of Science:
- Immunology
- Physiology
- Sepsis Pathophysiology
Background:
- Systemic complement activation can mimic sepsis hemodynamics.
- Sepsis is associated with reduced hepatic perfusion despite normal systemic circulation.
Purpose of the Study:
- To investigate the link between complement activation and reduced effective hepatic and renal blood flow in a murine sepsis model.
- To determine if complement activation accompanies blood flow redistribution in sepsis.
Main Methods:
- Rats underwent cecal ligation and puncture (CLP) or sham surgery.
- Cardiac output, mean arterial pressure, hematocrit, effective hepatic blood flow (EHBF), and effective renal blood flow (ERBF) were measured.
- Complement activity (CH50) was assessed before and after sepsis induction.
Main Results:
- CLP-induced sepsis led to reduced EHBF and ERBF despite normal cardiac output.
- Septic animals exhibited tachycardia and hypotension.
- Complement activity (CH50) decreased significantly in septic rats, indicating massive activation.
Conclusions:
- Complement activation is associated with impaired hepatic and renal perfusion in a murine model of sepsis.
- Further research is needed to establish the temporal relationship between complement activation and visceral flow changes.
Abstract:
The authors have shown that systemic activation of the complement system with either zymosan or cobra venom factor produces some of the hemodynamic changes characteristic of sepsis, specifically, a reduction in hepatic perfusion despite a normal or hyperdynamic systemic circulation. This study was undertaken to determine whether complement activation accompanied reductions in effective hepatic and renal blood flow (EHBF and ERBF, respectively) in a septic murine model previously demonstrated to be associated with flow redistribution. Rats underwent either cecal ligation and puncture (CLP) or sham laparotomy after a baseline blood sample was collected for complement assay. Eighteen hours later, thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, EHBF by galactose clearance, and ERBF by p-aminohippurate (PAH) clearance were determined. A second blood sample was collected for measurement of total hemolytic complement (CH50) by immune hemolysis of sheep erythrocytes and was compared to the t = 0 sample for calculation of per cent change in CH50. The cardiac output and hematocrit were normal in the CLP group relative to sham. The septic animals were tachycardic and slightly hypotensive, suggesting a diminished systemic vascular resistance. EHBF and ERBF fell dramatically in the septic group despite the normal cardiac output. Residual hemolytic complement activity was reduced to less than 40% of preseptic levels in the CLP group while sham values were no different than baseline, indicating massive complement activation in the septic animals. This study demonstrates an association between complement activation and hepatic and renal perfusion abnormalities in murine peritonitis. Work is underway to establish the temporal relationship between complement activation and visceral flow changes.(ABSTRACT TRUNCATED AT 250 WORDS)