Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats

N. A.M. Dekker, M. van Meurs, A. L.I. van Leeuwen, P. van Slyke, A. B.A. Vonk, C. Boer, C. E. van den Brom

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. Methods: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. Results: CPB immediately impaired microcirculatory perfusion [5 (4–8) vs 10 (7–12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8–25) vs 7 (1–12) μg g−1, P=0.04] and lung [and 23 (13–60) vs 6 (4–16) μg g−1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6–28) μg g−1 vs 23 (13–60) μg g−1, P=0.04], but not in kidney [10 (3–23) vs 12 (8–25) μg g−1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. Conclusions: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.

Original languageEnglish
Pages (from-to)1041-1051
Number of pages10
JournalBritish Journal of Anaesthesia
Volume121
Issue number5
Early online date19 Jun 2018
DOIs
Publication statusPublished - 2018

Cite this

@article{b5cdeb26b347409cbf28d9e521380aba,
title = "Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats",
abstract = "Background: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. Methods: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. Results: CPB immediately impaired microcirculatory perfusion [5 (4–8) vs 10 (7–12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8–25) vs 7 (1–12) μg g−1, P=0.04] and lung [and 23 (13–60) vs 6 (4–16) μg g−1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6–28) μg g−1 vs 23 (13–60) μg g−1, P=0.04], but not in kidney [10 (3–23) vs 12 (8–25) μg g−1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. Conclusions: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.",
keywords = "capillary permeability, cardiopulmonary bypass, microcirculation",
author = "Dekker, {N. A.M.} and {van Meurs}, M. and {van Leeuwen}, {A. L.I.} and {van Slyke}, P. and Vonk, {A. B.A.} and C. Boer and {van den Brom}, {C. E.}",
year = "2018",
doi = "10.1016/j.bja.2018.05.049",
language = "English",
volume = "121",
pages = "1041--1051",
journal = "British Journal of Anaesthesia",
issn = "0007-0912",
publisher = "Oxford University Press",
number = "5",

}

Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats. / Dekker, N. A.M.; van Meurs, M.; van Leeuwen, A. L.I.; van Slyke, P.; Vonk, A. B.A.; Boer, C.; van den Brom, C. E.

In: British Journal of Anaesthesia, Vol. 121, No. 5, 2018, p. 1041-1051.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats

AU - Dekker, N. A.M.

AU - van Meurs, M.

AU - van Leeuwen, A. L.I.

AU - van Slyke, P.

AU - Vonk, A. B.A.

AU - Boer, C.

AU - van den Brom, C. E.

PY - 2018

Y1 - 2018

N2 - Background: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. Methods: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. Results: CPB immediately impaired microcirculatory perfusion [5 (4–8) vs 10 (7–12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8–25) vs 7 (1–12) μg g−1, P=0.04] and lung [and 23 (13–60) vs 6 (4–16) μg g−1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6–28) μg g−1 vs 23 (13–60) μg g−1, P=0.04], but not in kidney [10 (3–23) vs 12 (8–25) μg g−1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. Conclusions: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.

AB - Background: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. Methods: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. Results: CPB immediately impaired microcirculatory perfusion [5 (4–8) vs 10 (7–12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8–25) vs 7 (1–12) μg g−1, P=0.04] and lung [and 23 (13–60) vs 6 (4–16) μg g−1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6–28) μg g−1 vs 23 (13–60) μg g−1, P=0.04], but not in kidney [10 (3–23) vs 12 (8–25) μg g−1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. Conclusions: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.

KW - capillary permeability

KW - cardiopulmonary bypass

KW - microcirculation

UR - http://www.scopus.com/inward/record.url?scp=85048730620&partnerID=8YFLogxK

U2 - 10.1016/j.bja.2018.05.049

DO - 10.1016/j.bja.2018.05.049

M3 - Article

VL - 121

SP - 1041

EP - 1051

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 5

ER -