Systemic and lung physiological changes in rats after intravascular activation of complement

Area of Science:

• Immunology
• Pathophysiology
• Shock Research

Background:

• Systemic complement activation is observed in various shock states.
• Complement activation products contribute to shock manifestations like hypotension and acidosis.

Purpose of the Study:

• To investigate the systemic effects of complement activation using cobra venom factor (CVF) in rats.
• To assess the impact of CVF-induced complement activation on hemodynamics, metabolic acidosis, vascular permeability, and lung function.

Main Methods:

• Systemic complement activation induced with cobra venom factor (CVF) in rats.
• Monitoring of blood pressure, metabolic acidosis (HCO3- concentration), vascular permeability (albumin extravasation), and arterial oxygenation (PO2).
• Evaluation of protective effects of prior complement depletion, neutrophil depletion, and cyclooxygenase inhibition.

Main Results:

• High-dose CVF induced circulatory collapse, severe metabolic acidosis, increased vascular permeability in lungs and gut, and hypoxemia.
• Prior complement depletion significantly protected against these CVF-induced abnormalities.
• Neutrophil depletion and cyclooxygenase inhibition mitigated lung injury but not systemic hemodynamics or gut permeability.

Conclusions:

• Systemic complement activation products significantly contribute to generalized shock abnormalities.
• Complement activation induces lung injury via neutrophil- and cyclooxygenase-dependent pathways.
• Complement activation impacts gut permeability through mechanisms independent of neutrophils and cyclooxygenase.