Microvascular changes explain the "two-hit" theory of multiple organ failure

Area of Science:

• Physiology
• Microcirculation
• Endothelial Function

Background:

• Sepsis following hemorrhagic shock can lead to multiple system organ failure (MSOF).
• The
• two-hit
• theory suggests sequential insults exacerbate organ damage.
• Intestinal vasoconstriction and hypoperfusion occur during bacteremia.

Purpose of the Study:

• To investigate intestinal microvascular endothelial cell function after sequential hemorrhage and bacteremia.
• To determine how prior hemorrhage affects the microvascular response to subsequent bacteremia.
• To explore the
• two-hit
• pathogenesis of MSOF.

Main Methods:

• Rats underwent hemorrhage and resuscitation, followed by Escherichia coli bacteremia.
• In vivo videomicroscopy assessed small intestine microcirculation.
• Endothelial-dependent (acetylcholine) and independent (nitroprusside) vasodilation were measured.

Main Results:

• Bacteremia caused arteriolar constriction, which was blunted after prior hemorrhage.
• Premucosal A3 vessels showed dilation after hemorrhage and bacteremia.
• Hemorrhage followed by bacteremia enhanced endothelial-dependent dilation in A3 vessels.

Conclusions:

• Hemorrhage alters intestinal microvascular endothelial control, favoring dilation in premucosal vessels.
• Enhanced dilator sensitivity in small premucosal vessels was observed.
• These findings support the
• two-hit
• theory, where initial stress modifies responses to subsequent inflammation.