Platelet-activating factor and sepsis-induced small intestinal microvascular hypoperfusion

Area of Science:

• Gastroenterology
• Microcirculation
• Sepsis Pathophysiology

Background:

• Sepsis and Platelet-Activating Factor (PAF) induce small intestinal (SI) hypoperfusion, potentially causing mucosal injury.
• PAF is suspected to impair SI microvascular blood flow during sepsis, but mechanisms remain unclear.
• Previous findings show sepsis causes SI arteriolar and venular constriction, contrasting with PAF's known arteriolar dilating effect in other tissues.

Purpose of the Study:

• To investigate the microvascular mechanisms by which PAF impairs SI blood flow.
• To determine if PAF mediates the microvascular effects observed during bacteremia through PAF receptor antagonism.

Main Methods:

• Intravital microscopy and velocimetry were used to measure SI arteriolar and venular diameters and red blood cell velocity.
• Animals were administered live Escherichia coli intravenously or topical PAF to the SI.
• PAF receptor antagonism was employed to assess PAF's role in bacteremia-induced microvascular changes.

Main Results:

• Both PAF and sepsis significantly reduced SI blood flow.
• Sepsis induced both arteriolar and venular constriction, while PAF primarily caused venular constriction.
• PAF receptor antagonism abolished the microvascular alterations associated with bacteremia, maintaining normal blood flow and venular diameter.

Conclusions:

• PAF impairs SI blood flow mainly through venular constriction.
• PAF is a key mediator of sepsis-induced microvascular dysfunction in the small intestine.
• Targeting PAF may be a therapeutic strategy to mitigate SI injury during sepsis.