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Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass

Koning, N. J., de lange, F., van Meurs, M., Jongman, R. M., Ahmed, Y., Schwarte, L. A., Amerongen, G. P. V. N., Vonk, A. B. A., Niessen, H. W., Baufreton, C. & Boer, C., Jun-2018, In : British Journal of Anaesthesia. 120, 6, p. 1165-1175 11 p.

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  • Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass

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DOI

  • Nick J. Koning
  • F. de lange
  • M. van Meurs
  • R. M. Jongman
  • Y. Ahmed
  • L. A. Schwarte
  • G. P. van Nieuw Amerongen
  • A. B. A. Vonk
  • H. W. Niessen
  • C. Baufreton
  • C. Boer

Background: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass.

Methods: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs.

Results: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P

Conclusions: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib- induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers.

Original languageEnglish
Pages (from-to)1165-1175
Number of pages11
JournalBritish Journal of Anaesthesia
Volume120
Issue number6
Publication statusPublished - Jun-2018

    Keywords

  • cardiopulmonary bypass, endothelium, microcirculation, ACUTE KIDNEY INJURY, ENDOTHELIAL BARRIER DYSFUNCTION, GELATINASE-ASSOCIATED LIPOCALIN, RESPIRATORY-DISTRESS-SYNDROME, CARDIAC-SURGERY, LUNG INJURY, MICROVASCULAR OXYGENATION, REPERFUSION INJURY, CAPILLARY DENSITY, IN-VIVO

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