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Pentoxifylline preserves small-intestine microvascular blood flow during bacteremia
G D Steeb1, M A Wilson, R N Garrison
1Department of Surgery, University of Louisville, KY 40292.
Background:
Intestinal mucosal ischemia with subsequent mucosal dysfunction has been implicated in the pathogenesis of ongoing sepsis and multiple systems organ failure. We have previously reported vasoconstriction and hypoperfusion in the intestinal microcirculation during sepsis. Efforts to improve microcirculatory blood flow during sepsis may lead to more effective treatment or prevention of multiple systems organ failure. Pentoxifylline improves survival and visceral organ perfusion in experimental sepsis and hemorrhage. The purpose of this study was to determine whether pentoxifylline would improve microvascular blood flow in the small intestine during bacteremia.
Methods:
In vivo videomicroscopy was used to quantitate alterations of the small-intestine microcirculation during Escherichia coli bacteremia in rats pretreated with either intravenous pentoxifylline or saline solution. Systemic hemodynamic and microvascular variables were measured every 15 minutes for 2 hours.
Results:
Tachycardia and increased cardiac output developed in bacteremic rats while they remained normotensive. Intestinal vasoconstriction and hypoperfusion occurred in bacteremic rats treated with saline solution. Microvessel diameters and blood flow remained within 5% to 10% of baseline in bacteremic rats pretreated with pentoxifylline. Pentoxifylline in nonbacteremic rats resulted in intestinal vasodilation and increased blood flow.
Conclusions:
Pentoxifylline prevented small-intestine vasoconstriction and preserved microvascular blood flow during hyperdynamic sepsis. Pentoxifylline in nonbacteremic rats increased microvascular blood flow.
Insights
Pentoxifylline prevents intestinal vasoconstriction and preserves microvascular blood flow during sepsis. This drug also increases blood flow in non-septic rats, suggesting a broad benefit for intestinal perfusion.
Area of Science:
- Sepsis Pathophysiology
- Microcirculation Research
- Pharmacological Interventions
Background:
- Sepsis-induced intestinal dysfunction contributes to organ failure.
- Intestinal vasoconstriction and hypoperfusion are key features of sepsis.
- Improving intestinal microcirculatory blood flow may prevent organ failure.
Purpose of the Study:
- To investigate the effect of pentoxifylline on small intestine microvascular blood flow during bacteremia.
- To determine if pentoxifylline can counteract sepsis-induced intestinal hypoperfusion.
Main Methods:
- Utilized in vivo videomicroscopy in a rat model of Escherichia coli bacteremia.
- Quantitated alterations in small intestine microcirculation.
- Measured systemic hemodynamic and microvascular variables over 2 hours.
Main Results:
- Bacteremic rats showed tachycardia and increased cardiac output but remained normotensive.
- Saline-treated bacteremic rats exhibited intestinal vasoconstriction and hypoperfusion.
- Pentoxifylline pretreatment prevented intestinal vasoconstriction, preserving microvascular blood flow.
- In non-bacteremic rats, pentoxifylline caused intestinal vasodilation and increased blood flow.
Conclusions:
- Pentoxifylline effectively prevents small intestine vasoconstriction and preserves microvascular blood flow in hyperdynamic sepsis.
- Pentoxifylline enhances microvascular blood flow in the intestine even in the absence of sepsis.