Endothelins mediate intestinal hypoperfusion during bacteremia.

We have previously reported that Escherichia coli bacteremia induces hypoperfusion and vasoconstriction of the rat small intestinal microcirculation. However, the mechanisms which mediate these responses are not clearly defined. Because serum levels of endothelins, a family of potent vasoconstrictor peptides, are increased during bacteremia, we postulated that endothelins contribute to intestinal hypoperfusion during infection. Using intravital microscopy, we characterized the effects of topically applied recombinant endothelin-1 on small intestinal arteriolar diameters and blood flow. Dose-dependent vasoconstriction of both large (A1) and small (A3) arterioles and hypoperfusion were observed. To assess whether endothelins contribute to alterations of the intestinal microcirculation during bacteremia, antiserum was used to inhibit endothelins during E. coli bacteremia. Endothelin inhibition resulted in restoration of blood flow and attenuation of vasoconstriction. Our results suggest that endothelins contribute to intestinal hypoperfusion and arteriolar vasoconstriction during bacteremia.

Microvascular vasoconstriction and mucosal hypoperfusion of the rat small intestine during bacteremia.

Our previous studies have demonstrated that bacteremia induces vasoconstriction and hypoperfusion of the small intestinal microcirculation. The present study used time-transit doppler flowmetry, intravital microscopy, and laser doppler fluximetry to measure superior mesenteric artery (SMA) blood flow, intestinal microvascular blood flow, and mucosal perfusion. The aim of this study was to determine the relative importance of the intestinal macro- and microcirculations in the development of mucosal hypoperfusion. Animals were infused with 5 x 10(8) colony-forming units of Escherichia coli/100 g body weight or saline as control. Bacteremia induced a normotensive, normodynamic state. SMA blood flow was unaffected by bacteremia, but arteriolar vasoconstriction (approximately -30%) and microvascular hypoperfusion (approximately -70%) occurred. Mucosal perfusion decreased by 40% from baseline, and was temporally correlated with microvascular hypoperfusion. From these data, we conclude that the microcirculation has a central role in the development of mucosal hypoperfusion during bacteremia.

Pentoxifylline preserves small-intestine microvascular blood flow during bacteremia.

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.