CVF-induced decomplementation: effect on lung transvascular protein flux after thrombin

Area of Science:

• Pulmonary Circulation
• Inflammation and Immunology
• Hemodynamics

Background:

• Thrombin-induced pulmonary microembolism causes significant changes in pulmonary hemodynamics and fluid exchange.
• The role of complement activation in mediating these changes is not fully understood.
• Granulocyte activation is implicated in inflammatory responses within the pulmonary vasculature.

Purpose of the Study:

• To investigate the effect of cobra venom factor (CVF), a complement inhibitor, on thrombin-induced pulmonary microembolism.
• To determine how CVF treatment influences pulmonary hemodynamics and transvascular fluid and protein exchange.
• To assess the impact of CVF on granulocyte function in response to pulmonary embolism.

Main Methods:

• Unanesthetized sheep with lung lymph fistulas were used.
• Tranexamic acid was administered to inhibit fibrinolysis.
• Thrombin was infused to induce pulmonary microembolism, with comparisons between control and CVF-treated groups.

Main Results:

• CVF treatment significantly reduced hemolytic complement activity.
• CVF-treated sheep exhibited smaller increases in pulmonary arterial pressure, pulmonary vascular resistance, and lymph protein clearance post-thrombin infusion compared to controls.
• Granulocytes from CVF-treated sheep showed reduced migration and oxygen radical generation in response to inflammatory stimuli.

Conclusions:

• Complement activation plays a key role in the hemodynamic and fluid exchange alterations following thrombin-induced pulmonary microembolism.
• CVF treatment attenuates these adverse effects, likely by inhibiting complement-mediated granulocyte activation and function.
• These findings suggest a therapeutic potential for complement inhibition in managing pulmonary microembolic events.