Microvascular perfusion is impaired in a rat model of normotensive sepsis.

Lam, Calvin; Tyml, Karel; Martin, Claudio M.; Sibbald, William J.

doi:10.1172/jci117562

Cited by 334 publications

(235 citation statements)

References 31 publications

(26 reference statements)

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“…21 Normotensive sepsis induces absence of capillary flow 22 and alters leukocyte-endothelium interactions. 19,23,24 Smalley et al 24 found that CLP significantly increases leukocyte adherence and infiltration into the upper gastrointestinal tract 4 hours after intervention.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Observation of Mesenteric Leukocyte-Endothelial Interactions After Cecal Ligation/Puncture and Surgical Sepsis Source Control

Nakagawa

Jukemura

Aikawa

et al. 2007

Clinics

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Nakagawa NK; Jukemura J, Aikawa P, Nogueira RA, Poli-de-Figueiredo LF, and Sannomiya P. In vivo observation of mesenteric leukocyte-endothelial interactions after cecal ligation/puncture and surgical sepsis source control. Clinics. 2007;62(3):321-6. PURPOSE: Cecal ligation and puncture (CLP) has been used as a useful model for the induction of polymicrobial sepsis. Necrotic tissue resection and peritoneal lavage (REL) are the surgical procedures for controlling perforated appendicitis. The aim of this study was to evaluate leukocyte-endothelial interactions in the rat mesentery in vivo after CLP and REL. METHODS: Thirty-seven male Wistar rats (250-300 g) underwent laparotomy and were randomly assigned to the following groups: 1) SHAM; 2) CLP: animals submitted to CLP, 3) CLP+REL: animals submitted to CLP and REL. Mesenteric leukocyteendothelial interactions were studied by intravital microscopy assessed once in each animal (3-5 postcapillary venules, 15-25 µm diameter) 24 hours after intervention. Follow-up was performed in all animals; this included analysis of glycemia, lactate, hematocrit, white blood cell count as well as a functional score that was the sum of scoring on the following parameters: alertness, mobility, piloerection, diarrhea, encrusted eyes, and dirty nose and tail. RESULTS: None of the animals showed significant changes in body weight (265 ± 20 g) or in hematocrit levels (46% ± 2%) during the experimental protocol. Compared to SHAM animals, CLP animals showed an increased number of rolling (2x), adherent, and migrating leukocytes (7x) in the mesenteric microcirculation, an increase in blood glucose (136 ± 8 mg/dL), lactate (3.58 ± 0.94 mmol/L), white cell count (23,570 ± 4,991 cells/mm 3 ) and functional alterations (score 11 ± 1), characterized by impaired alertness and mobility, and presence of piloerection, diarrhea, encrusted eyes, and dirty nose and tail. The REL procedure normalized the number of rolling, adherent, and migrated leukocytes in the mesentery; glycemia; lactate; and white blood cell count. The REL procedure also improved the functional score (7 ± 1). CONCLUSION: Local and systemic inflammation was induced by CLP, while REL completely overcame the inflammatory process.

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Section: Discussionmentioning

confidence: 99%

In Vivo Observation of Mesenteric Leukocyte-Endothelial Interactions After Cecal Ligation/Puncture and Surgical Sepsis Source Control

Nakagawa

Jukemura

Aikawa

et al. 2007

Clinics

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“…Patients with sepsis show reductions in the proportion of perfused capillaries,53 and in animal models of normotensive sepsis, the density of capillaries with either intermittent or no flow is elevated, while the normal response to vasodilators is reduced 54, 55. Notably, death from MOF after septic shock is antedated by reductions in the proportion of perfused sublingual capillaries compared to survivors, in spite of identical systemic hemodynamic and oxygenation variables 56.…”

Section: Evidence Of Changes In Capillary Density and Cth From Directmentioning

confidence: 99%

Microcirculatory dysfunction and tissue oxygenation in critical illness

Østergaard

Granfeldt

Secher

et al. 2015

Acta Anaesthesiol Scand

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Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high.The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen.We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns.

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“…Several trials in which OPS was used to evaluate microcirculation in sepsis were recently published ( (2) 1994 J Clin Invest.…”

Section: Evidence Of Septic Microcirculatory Changesmentioning

confidence: 99%

“…(2)(3)(4) During this period of research, human studies were dependent upon the large microscopes that were used for periungual microcirculation assessments. These assessments showed a reduced rate of capillary flow in normotensive patients with fever.…”

Section: Introductionmentioning

confidence: 99%