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Platelet-activating factor and sepsis-induced small intestinal microvascular hypoperfusion
M F Bar-Natan1, M A Wilson, D A Spain
1Department of Surgery, University of Louisville, Kentucky.
Abstract:
Platelet-activating factor (PAF) and bacteremia both cause small intestinal (SI) hypoperfusion which may contribute to mucosal injury, and PAF has been postulated to mediate impaired SI microvascular blood flow during sepsis. Our previous studies demonstrate that sepsis-induced SI hypoperfusion is associated with both arteriolar and venular constriction, but the microvascular mechanisms by which PAF impairs SI blood flow are not well defined. Microcirculation studies in other tissues indicate that PAF is an arteriolar dilator, but this effect in the SI would not explain PAF-mediated hypoperfusion. We studied the effects of PAF on SI microvessels to characterize the microvascular mechanisms which mediate PAF-induced hypoperfusion. We also determined the role of PAF as a mediator of microvascular effects in the intestine during bacteremia by PAF receptor antagonism. Animals received either 10(9) live Escherichia coli IV or PAF applied topically to the SI (30, 80, and 300 nM). Arteriolar and venular diameters and red blood cell velocity (A1, V1) were measured with intravital microscopy and velocimetry. Both PAF and sepsis resulted in impaired SI blood flow (maximum decrease in blood flow -37 and 65%, respectively), but sepsis was associated with both arteriolar and venular constriction (20 and 30% diameter reduction each), whereas PAF produced only venular constriction (50% diameter reduction). Inhibition of PAF action prevented the microvascular alterations of bacteremia (blood flow unchanged, P < 0.05; venular diameter unchanged, P < 0.05), suggesting that PAF is an important mediator of these responses.
Insights
Platelet-activating factor (PAF) causes small intestinal hypoperfusion by constricting venules. Blocking PAF prevents sepsis-induced microvascular changes, indicating PAF mediates these effects during bacteremia.
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.