Postoperative microcirculatory perfusion and endothelial glycocalyx shedding following cardiac surgery with cardiopulmonary bypass

Abstract

We investigated microcirculatory perfusion disturbances following cardiopulmonary bypass in the early postoperative period and whether the course of these disturbances mirrored restoration of endothelial glycocalyx integrity. We performed sublingual sidestream dark field imaging of the microcirculation during the first three postoperative days in patients who had undergone on-pump coronary artery bypass graft surgery. We calculated the perfused vessel density, proportion of perfused vessels and perfused boundary region. Plasma was obtained to measure heparan sulphate and syndecan-1 levels as glycocalyx shedding markers. We recruited 17 patients; the mean (SD) duration of non-pulsatile cardiopulmonary bypass was 103 (18) min, following which 491 (29) ml autologous blood was transfused through cell salvage. Cardiopulmonary bypass immediately decreased both microcirculatory perfused vessel density; 11 (3) vs. 16 (4) mm.mm^-2 , p = 0.052 and the proportion of perfused vessels; 92 (5) vs. 69 (9) %, p < 0.0001. The proportion of perfused vessels did not increase after transfusion of autologous salvaged blood following cardiopulmonary bypass; 72 (7) %, p = 0.19 or during the first three postoperative days; 71 (5) %, p < 0.0001. The perfused boundary region increased after cardiopulmonary bypass; 2.2 (0.3) vs. 1.9 (0.3) μm, p = 0.037 and during the first three postoperative days; 2.4 (0.3) vs. 1.9 (0.3) μm, p = 0.003. Increased plasma heparan sulphate levels were inversely associated with the proportion of perfused vessels during cardiopulmonary bypass; R = -0.49, p = 0.02. Plasma syndecan-1 levels were inversely associated with the proportion of perfused vessels during the entire study period; R = -0.51, p < 0.0001. Our study shows that cardiopulmonary bypass-induced acute microcirculatory perfusion disturbances persist in the first three postoperative days, and are associated with prolonged endothelial glycocalyx shedding. This suggests prolonged impairment and delayed recovery of both microcirculatory perfusion and function after on-pump cardiac surgery.

Keywords: blood oxygen transport, oxygen delivery to tissues: factors impacting; cardiopulmonary bypass management; endothelial glycocalyx; microcirculation.

Figure 1

Red blood cell (RBC) flow patterns under normal conditions before cardiopulmonary bypass (left panel) and after bypass (right panel). Under normal conditions, red blood cells preferentially flow within the centre of microvessels, creating a RBC‐free permeable luminal layer. This minimises the contact between RBCs and endothelial cells, and decreases flow resistance. After bypass, the thickness of the RBC‐free luminal layer decreases, which might theoretically result in altered flow resistance. RBC, red blood cell.

Figure 2

Examples of microcirculatory perfusion recordings in a patient before cardiopulmonary bypass (panel a); during bypass (panel b); after infusion of cell salvaged red blood cells after weaning from bypass (panel c) and 72 h after surgery (panel d).

Figure 3

Haemoglobin concentrations (panel a), RM p < 0.001; haematocrit levels (panel b), RM p < 0.001; perfused vessel density (panel c), RM with Greenhouse–Geiser correction, p = 0.05; proportion of perfused vessels (panel d), RM with Greenhouse–Geiser correction, p < 0.0001; perfused boundary region (panel e), RM with Greenhouse–Geiser correction, ns; and capillary red blood cell concentration (panel f), RM with Greenhouse–Geiser correction, ns: before CPB; during CPB; after infusion of cell salvaged red blood cells after weaning from CPB and 24 h and 72 h following surgery. Values are mean (SD). *p < 0.05, ^#p < 0.05 vs. Pre‐op. PVD, perfused vessel density; PPV, proportion of perfused vessels; PBR, perfused boundary region; CPB, cardiopulmonary bypass; RM, RM ANOVA. RM, repeated measures; Pre‐op, pre‐operative; Postop, postoperative; CPB, cardiopulmonary bypass.

Figure 4

Plasma concentrations of heparan sulphate (panel a) and syndecan‐1 (panel b) before CPB; during CPB; after infusion of cell salvaged red blood cells and 24 h and 72 h following surgery. Values are mean (SD). *p < 0.05, ^#p < 0.05 vs. Pre‐op; Pre‐op, pre‐operative; postop, postoperative; CPB, cardiopulmonary bypass.

Figure 5

Associations between plasma glycocalyx shedding molecules, heparan sulphate and syndecan‐1, and perfused boundary region (PBR, panel a + c); microcirculatory perfusion (PPV, panel b + d); and the ratio of capillary to systemic haematocrit (panel e + f). Values are presented with 95%CI. PBR, perfused boundary region; PPV, proportion of perfused vessels.