Angiopoietin-1 mimetic restores microcirculatory perfusion after cardiopulmonary bypass in a rat model 

N.A.M. Dekker, The Netherlands, E-Mail: n.dekker@vumc.nl

Dekker N.A.M. (1), van den Brom C.E. (1), van Leeuwen A.L.I. (1,2), Koning N.J. (1), Vonk A.B.A.2, Boer C. (1).
(1) Departments of Anesthesiology and (2) Cardiothoracic Surgery, VU University Medical Center, Amsterdam, The Netherlands.

Background and Goal of Study: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by microvascular leakage. The Angiopoietin/Tie2 system might preserve endothelial barrier function and attenuate microvascular leakage. This study investigated the effects of an Angiopoietin-1 mimetic on microcirculatory perfusion in a rat CPB model.
 
Materials and methods: Male rats were subjected to 75 minutes of CPB after treatment with an angiopoietin-1 mimetic (Ang1mim; n=5) or PBS (n=5). Intravital microcirculatory perfusion was measured in the cremaster muscle at baseline and five time points until 60 minutes after CPB.

Results and discussion: Onset of CPB resulted in comparable haematocrit levels (21.0 ± 1.0%, P=0.02 and 18.8 ± 0.9%, P< 0.001) in the PBS and Ang1mim groups, respectively. In the PBS group, this was accompanied by reduced proportion of perfused capillaries from 86.6 ± 2.6% to 59.5 ± 5.3%, P=0.002 and increased number of stopped vessels from 12.1 ± 3.1% to 40.1 ± 5.1% P=0.002, which progressed after CPB. In contrast, Ang1mim pretreated rats showed minimal reduction in perfused vessel proportion during CPB from 93.5 ± 2.2% to 79.4 ± 3.7%, P=0.01 which restored after CPB to 80.9±5.9%, P=0.07 vs. baseline. Moreover, CPB-induced stopped vessels returned to baseline one hour after weaning from CPB in the Ang1mim group from 5.1±2.2 to 18.3±6.0, P=0.07 after CPB.

Conclusion(s): Intervening with an Angiopoietin-1 mimetic attenuates and restores CPB-induced microcirculatory perfusion disturbances suggesting that therapeutic targeting the Angiopoietin/Tie2 system may contribute to preserved microcirculatory function during extracorporeal circulation.