Abstract
Background. Altered intestinal blood flow during systemic inflammation leads to organ dysfunction.
Mucosal ischemia occurs during sepsis despite an increase in portal blood flow. We
hypothesized that separate mechanisms are active in the large resistance and small
mucosal microvessels to account for this dichotomy. Methods. Chronic infection was induced in rats by bacterial inoculation (Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge. Separate groups were studied at 24 and 72 hours
after a single inoculation of bacterium or 24 hours after a second inoculation (ie,
72 hours of sepsis). Time-matched controls were used for each group. Intravital microscopy
of the terminal ileum was used to assess endothelial-dependent vasodilation to acetylcholine
(10−9 to 10−5 mol/L) in resistance (A1) and premucosal (A3) arterioles. Threshold sensitivity (-log of 20% response dose) was calculated from
dose response curves for each animal. Results. Vasodilator sensitivity to acetylcholine in A1 arterioles was significantly decreased at 24 hours, and these changes persisted up
to 72 hours after a single bacterial inoculation. There was no change in the dilator
sensitivity of A3 arterioles after a single inoculation. When there was a challenge with a second bacterial
inoculation, there was a reversal of the A1 dilator response and an increase in A3 sensitivity. Conclusions. An initial septic event results in a decrease in dilator reactivity in the resistance
A1 arterioles that persists for at least 72 hours. A sustained septic challenge results
in increased dilator reactivity in both A1 and A3 vessels. This enhanced sensitivity during sepsis suggests that more than 1 therapeutic
approach to preservation of intestinal blood flow will be necessary. (Surgery 2000;128:513-9.)
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References
- Spectrum of cardiovascular function during gram-negative sepsis.Prog Cardiovasc Dis. 1981; 23: 279-297
- Intrinsic myocardial dysfunction during endotoxemia: dependent or independent of myocardial ischemia?.Circ Shock. 1990; 30: 63-76
- EDRF as a possible mediator of sepsis-induced arteriolar dilation in skeletal muscle.Am J Physiol. 1992; 31: H880-H887
- Nitric oxide: physiology, pathophysiology, and pharmacology.Pharmacol Rev. 1991; 43: 109-142
- Evidence of increased nitric oxide production in patients with the sepsis syndrome.Circ Shock. 1993; 41: 77-81
- The discovery of nitric oxide in the vessel wall: a unifying concept in the pathogenesis of sepsis.Arch Surg. 1993; 128: 396-401
- Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock.Lancet. 1991; 338: 1557-1558
- Effects of cytokines tumor necrosis factor α and interleukin 1β on endotoxin-mediated inhibition of endothelium-derived relaxing factor bioactivity and nitric oxide production in vascular endothelium.Shock. 1994; 1: 73-78
- Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia.Circ Res. 1993; 72: 539-551
- Endothelium-dependent relaxation is depressed at the macro- and microcirculatory levels during sepsis.Am J Physiol. 1995; 269: R988-R994
- Subacute sepsis impairs vascular smooth muscle contractile machinery and alters vasoconstrictor and dilator mechanisms.J Surg Res. 1999; 83: 75-80
- Chronic hyperdynamic sepsis in the rats: characterization of the animal model.Circ Shock. 1988; 25: 231-244
- Absorptive hyperemia restores intestinal blood flow during Escherichia coli sepsis in the rat.Arch Surg. 1990; 125: 1573-1576
- Preparation of the rat intestinal muscle and mucosa for quantitative microcirculatory studies.Microvasc Res. 1976; 11: 103-110
- Detrimental hemodynamic effects of nitric oxide synthase inhibition in septic shock.Arch Surg. 1994; 129: 149-156
- Inhibition of nitric oxide synthesis is detrimental during endotoxemia.Arch Surg. 1994; 129: 142-148
- Differential induction of nitric oxide synthase in hepatocytes during endotoxemia and the acute-phase response.Arch Surg. 1994; 129: 165-171
- Differential effects of acetylcholine and bradykinin on prostanoid release from the rat mesenteric bed: role of endothelium and of nitric oxide.Prostaglandins Leukot Essent Fatty Acids. 1997; 56: 253-258
- Endothelium-derived hyperpolarizing factor but not NO reduces smooth muscle Ca2+ during acetylcholine-induced dilation of microvessels.Br J Pharmacol. 1999; 128: 124-134
- Pentobarbital-sensitive EDHF comediates ACH-induced arteriolar dilation in the hamster microcirculation.Am J Physiol. 1999; 276: H1527-H1534
- Enhanced prostanoid-mediated vasorelaxation in pulmonary arteries isolated during experimental endotoxemia.Shock. 1999; 11: 436-442
- Glucose-induced intestinal hyperemia is mediated by nitric oxide.J Surg Res. 1997; 72: 146-154
- Glucose and glutamine gavage increase portal vein nitric oxide metabolite levels via adenosine A2b activation.J Surg Res. 1999; 84: 57-63
- Vasomotion induces regular major oscillations in jejeunal mucosal tissue oxygenation.Am J Physiol. 1994; 266: G978-G986
- Rotavirus-induced changes in the microcirculation of intestinal villi of neonatal mice in relation to the induction and persistence of diarrhea.J Pediatr Gastroenterol Nutr. 1991; 12: 111-120
Article info
Footnotes
*Supported by VA Merit Review Funding (DAS and RNG).
**Reprint requests: David A. Spain, MD, Department of Surgery, University of Louisville, Louisville, KY 40292.
★Surgery 2000;128:513-9
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
