Article
In vivo analysis of leukocyte-endothelium interactions and microhemodynamics in the pulmonary microcirculation during polymicrobial sepsis
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Authors
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Nils T. Veith
- University of Saarland, Department of Anatomy and Cell Biology, Homburg
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Jonas Roller
- Lund University, Department of Surgery, Malmö University Hospital, Malmö
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René Schramm
- Ludwig-Maximilians University, Clinic of Cardiac Surgery, München
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Matthias W. Laschke
- University of Saarland, Institute for Clinical & Experimental Surgery, Homburg a.d. Saar
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Thomas Tschernig
- University of Saarland, Department of Anatomy and Cell Biology, Homburg
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Michael D. Menger
- University of Saarland, Institute for Clinical & Experimental Surgery, Homburg a.d. Saar
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Bengt Jeppsson
- Lund University, Department of Surgery, Malmö University Hospital, Malmö
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Henrik Thorlacius
- Lund University, Department of Surgery, Malmö University Hospital, Malmö
| Published: | May 20, 2011 |
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Outline
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Introduction: Acute lung injury is a key component in sepsis. Leukocytes are essential for host defence against invading microorganisms, but excessive accumulation in the lung may cause organ injury. The spatial and temporal characteristics of leukocyte recruitment in the pulmonary microcirculation in septic lung injury are not known. Therefore the aim of the present study was to develop an in vivo model to study leukocyte-endothelial cell interactions and microhemodynamics in the pulmonary microcirculation during polymicrobial sepsis.
Materials and methods: Polymicrobial sepsis was induced in 11 C57BL/6 mice by cecal ligation and puncture (CLP). Animals were anaesthetized and mechanically ventilated after 4h (n=6) and 18h (n=5). A thoracotomy was performed to exteriorize the right side of the thorax. By means of intravital fluorescence microscopy, leukocyte-endothelial cell interaction and microhemodynamic parameters were analyzed in arterioles, venules and capillaries of the lung. Non-treated, healthy animals (n=5) served as controls.
Results: CLP significantly increased the number of adherent leukocytes after 4h in venules (600±162/mm²), arterioles (232±57/mm²) and capillaries (32±2/region of interest (ROI)) when compared to control animals (139±26/mm², 21±16/mm², 13±2/ROI; p<0.05). While after 18h the number of adherent leukocytes in arterioles (236±75/mm²) and capillaries (36±7/ROI) was still elevated, a decreased number of adherent leukocytes could be observed within venules (301±50/mm²) when compared to 4h CLP. Rolling leukocytes were found to be decreased both in venules (0.3±0.2/min) and arterioles (0.1±0.1/min) after 18h CLP (control: 2.2±1/min and 1.9±0.7/min). While microhemodynamic parameters in arterioles and venules of the different groups were comparable, functional capillary density was decreased significantly after 18h CLP (653±36 cm/cm²; control: 892±86cm/cm²).
Conclusion: Our data show that the leukocyte-endothelial cell interactions within pulmonary venules are elevated in the early phase of sepsis. In contrast, leukocytes trapped in pulmonary capillaries are constantly increased under septic conditions, indicating different modes of leukocyte accumulation in different parts of the lung.
