Systemic Complement Activation Produces Hemodynamic Changes Characteristic of Sepsis

Schirmer, William J.; Schirmer, James M.; Naff, George B.; Fry, Donald E.

doi:10.1001/archsurg.1988.01400270050007

Cited by 48 publications

(13 citation statements)

References 11 publications

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“…Second, complement activation can mimic sepsis. Animals inoculated with homologous serum in which the complement had been activated by exposure to zymosan developed hyperdynamic shock similar to that found in septic patients (37,44). Finally, prevention of the formation of C5a mitigates sepsis.…”

supporting

confidence: 55%

Complement Activation by Whole Endotoxin Is Blocked by a Monoclonal Antibody to Factor B

Clardy¹

1994

Critical Care Medicine

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Sepsis is both a common and, despite present-day therapy, a serious disease. The pathophysiology of the septic response is a complex, multifactorial phenomenon which in part involves the activation of complement by bacterial endotoxin. A monoclonal antibody to human complement factor B, code-named lH5, which was capable of specifically inhibiting the alternative pathway of complement activation at concentrations as low as 1 ,ug/ml, is described. This agent had no effect on the classical pathway of complement activation. It was capable of preventing the activation of complement by even high concentrations (0.1 mg/ml) of whole endotoxin; however, it was ineffective in preventing activation of complement by endotoxin derived from a rough mutant. This agent could potentially be used in the treatment of sepsis.Sepsis is a systemic inflammatory response syndrome caused by the products of infection, particularly gram-negative bacteria. It is characterized initially by hyperdynamic shock resulting from a profound decrease in systemic vascular resistance. Subsequently, perturbations of the lungs, heart, kidneys, liver, and coagulation cascade can result in multiple organ failure.

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supporting

confidence: 55%

Complement Activation by Whole Endotoxin Is Blocked by a Monoclonal Antibody to Factor B

Clardy¹

1994

Critical Care Medicine

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“…Mice in which complement was systemically activated by zymosan or cobra venom factor exhibit organ perfusion abnormalities and alterations in hemodynamic parameters similar to those abnormalities observed during sepsis [8,29,30]. These deleterious effects have been attributed primarily to the terminal components of the complement cascade, including the complementderived membrane attack complex, and complement component C5a.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas local and regulated complement activation is an important part of host defense, systemic activation of complement can result in changes in hemodynamic parameters leading to shock [8], and persistent elevations of the complement-derived chemotaxins C3a and C4a correlate with increased mortality following sepsis [9]. High levels of another complementderived chemoattractant, C5a, have also been associated with increased remote organ damage following surgical peritonitis in both rats and mice.…”

mentioning

confidence: 99%

Vaccinia Virus Complement Control Protein Increases Early Bacterial Clearance during Experimental Peritonitis

Scott

Burch²,

Jha³

et al. 2003

Surgical Infections

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“…[1][2][3][4] However, the significance of intestinal bacterial translocation in the development of systemic sepsis has been disputed. [5][6][7] Nevertheless, it currently is generally accepted that the gut-derived LPS may contribute to morbidity and mortality of the shock syndrome. In this respect, Rush et al8 demonstrated a direct relationship between the duration of the shock period and incidence of LPS occurrence in plasma after hemorrhagic shock in rats.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Endotoxin and Tumor Necrosis Factor Appearance in Portal and Systemic Circulation After Hemorrhagic Shock in Rats

Jiang¹,

Bahrami²,

Leichtfried³

et al. 1995

Annals of Surgery

139

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ObjectiveThis study was performed to investigate gut-derived bacterial translocation and the time course of endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF) appearance, both in portal and systemic circulation. Summary Background DataThe significance of intestinal bacteria/endotoxin translocation or TNF formation in the development of systemic sepsis has been disputed. MethodsA rat model of hemorrhagic shock (30-35 mm Hg for 90 min) and resuscitation was used. ResultsBacterial translocation was histologically observed in the small intestinal wall 30 minutes after resuscitation. A significant increase in LPS concentrations was found in the portal vein (91.7 ± 30.6 pg/mL) at 90 minutes, which remained steady until 150 minutes after shock. Lipopolysaccharide increased in the systemic circulation, the levels became significant at 120 minutes, and peaked (66.5 ± 39.2 pg/mL) 150 minutes after shock. Tumor necrosis factor concentrations were found to be significantly elevated in both portal and systemic circulation (75.6 ± 22.1 vs. 58.4 ± 14.1 pg/mL) at 90 minutes post-shock. Although there was no further increase in TNF concentration in the portal blood, TNF peaked (83.5 ± 17.7 pg/mL) in systemic circulation at 120 minutes and still was markedly increased at 150 minutes post-shock. In addition, higher LPS and TNF concentrations in systemic circulation were found in the nonsurvivors than in the surviving animals at the end of resuscitation. ConclusionsThese results suggest that hemorrhagic shock may lead to early bacterial translocation in the intestinal wall and transient access of gut-derived LPS and LPS-induced mediators into the circulation predominantly via the portal circulation. 100

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Systemic Complement Activation Produces Hemodynamic Changes Characteristic of Sepsis

Cited by 48 publications

References 11 publications

Complement Activation by Whole Endotoxin Is Blocked by a Monoclonal Antibody to Factor B

Complement Activation by Whole Endotoxin Is Blocked by a Monoclonal Antibody to Factor B

Vaccinia Virus Complement Control Protein Increases Early Bacterial Clearance during Experimental Peritonitis

Kinetics of Endotoxin and Tumor Necrosis Factor Appearance in Portal and Systemic Circulation After Hemorrhagic Shock in Rats

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