Macromolecular leak from extrasplenic lymphatics during endotoxemia

Area of Science:

• Physiology
• Pathophysiology
• Microcirculation

Background:

• The spleen plays a key role in maintaining blood volume.
• Endotoxemia may cause dysfunction in the extrasplenic pathway.
• Increased lymphatic 'leakiness' may lead to fluid loss and affect blood volume homeostasis.

Purpose of the Study:

• To investigate the functionality of the extrasplenic pathway during endotoxemia.
• To determine if lipopolysaccharide (LPS) affects extrasplenic lymphatic function.
• To assess the contribution of extrasplenic fluid loss to hypovolemia in sepsis.

Main Methods:

• Intravital microscopy was used to study extrasplenic and ileal mesenteric microcirculation in anesthetized rats.
• Fluorescently labeled albumin (FITC-BSA) was used to track macromolecular leakage.
• Lipopolysaccharide (LPS) was administered to induce endotoxemia.

Main Results:

• LPS induced constriction of extrasplenic venules and dilation of lymphatics.
• Macromolecular leakage from extrasplenic venules and lymphatics was observed during endotoxemia.
• A decrease in mean arterial pressure was noted concurrently with fluid losses.

Conclusions:

• Extrasplenic lymphatics can leak large protein molecules into interstitial spaces during endotoxemia.
• This leakage represents a dysfunction in the typically unidirectional lymphatic uptake.
• Fluid loss from extrasplenic lymphatics may contribute to hypovolemia and hypotension in sepsis.