Cardiopulmonary bypass increases endothelial dysfunction after pulmonary ischaemia-reperfusion in an animal model

Abstract

OBJECTIVES Endothelial dysfunction during ischaemia-reperfusion (IR) is a major cause of primary graft dysfunction during lung transplantation. The routine use of cardiopulmonary bypass (CPB) during lung transplantation remains controversial. However, the contribution of CPB to pulmonary endothelial dysfunction remains unclear. The objective was to investigate the impact of CPB on endothelial dysfunction in a lung IR rat model. METHODS Rats were allocated to 4 groups: (i) Sham, (ii) IR, (iii) CPB and (iv) IR-CPB. The primary outcome was the study of pulmonary vascular reactivity by wire myograph. We also assessed glycocalyx degradation by enzyme-linked immunosorbent assay and electron microscopy and both systemic and pulmonary inflammation by enzyme-linked immunosorbent assay and immunohistochemistry. Rats were exposed to 45 min of CPB and IR. We used a CPB model allowing femoro-femoral support with left pulmonary hilum ischaemia for IR. RESULTS Pulmonary endothelium-dependent relaxation to acetylcholine was markedly reduced in the IR-CPB group (10.7 ± 9.1%) compared to the IR group (50.5 ± 5.2%, P < 0.001), the CPB group (54.1 ± 4.7%, P < 0.001) and the sham group (80.8 ± 6.7%, P < 0.001), suggesting that the association of pulmonary IR and CPB increases endothelial dysfunction. In IR-CPB, IR and CPB groups, vasorelaxation was completely abolished when inhibiting nitric oxide synthase, suggesting that this relaxation process was mainly mediated by nitric oxide. We observed higher syndecan-1 plasma levels in the IR-CPB group in comparison with the other groups, reflecting an increased degradation of glycocalyx. We also observed higher systemic inflammation in the IR-CPB group as shown by the increased plasma levels of IL-1β, IL-10. CONCLUSIONS CPB significantly increased the IR-mediated effects on pulmonary endothelial dysfunction. Therefore, the use of CPB during lung transplantation could be deleterious, by increasing endothelial dysfunction.

Combined Electron Microscopy Approaches for Arterial Glycocalyx Visualization

“…For TEM investigations, analyses were performed on the 2 groups from this study: the sham group ( n = 2) and a group combining pulmonary IR and CPB (IR-CPB group) ( n = 2). Regarding the vascular response, we found the same results in these 2 groups as in the study previously described by Selim et al ( 9 ). Data showed increased plasma levels of the glycocalyx marker syndecan-1 in the IR-CPB group compared to the sham group (IR-CPB 23.6 ± 0.3 μg/ml; sham 19.6 ± 0.2 μg/ml).…”

“…Furthermore, our observations suggest that IR-CPB induces a large depletion area of glycocalyx at the outer surface of the endothelium. Previous work ( 9 ) on the same model, revealed an increase of blood syndecan-1 level when IR was associated with CPB, supporting the hypothesis of glycocalyx degradation. In addition, we noticed an increased number of vesicles at the apical side, suggesting a compensatory mechanism by which the endothelium tends to restore the pool of proteoglycans.…”

“…The routine use of CPB during the surgical procedure is controversial mainly due to its unclear contribution to endothelial dysfunction. A recent study ( 9 ) showed that CPB associated with IR further impaired endothelial function. Exploration by combined EM approaches ( Figures 5A,B ) reveals first a less regular distribution of glycocalyx at the endothelial surface as in the physiological state, exhibiting a cell coat more packed ( Figures 5A,B ).…”

The endothelial glycocalyx in critical illness: A pediatric perspective

“…Following completion of surgery and liberation from CPB, areas of hypoperfusion and ischemia are flooded with oxygen-rich blood, leading to reperfusion injury from mitochondrial dysfunction and depletion of anti-oxidant reserves. Ischemia-reperfusion injury then drives the activation of complement [202] and upregulation of pro-inflammatory cytokines [203] that promote the release of EG-eroding sheddases [204] .…”

Priming of Cardiopulmonary Bypass with Human Albumin Decreases Endothelial Dysfunction after Pulmonary Ischemia–Reperfusion in an Animal Model

“…This topic is still controversial in LTx teams [ 4 ]. In a cardiopulmonary bypass (CPB) model associated with pulmonary IR in rats, we have recently shown that CPB significantly increased the effects of pulmonary IR on pulmonary vascular dysfunction, on systemic and tissular inflammation, and on glycocalyx degradation [ 5 ]. Indeed, the study of pulmonary arteries’ vasoreactivity has shown that pulmonary endothelium-dependent relaxation to acetylcholine was markedly reduced in the group with CPB associated with pulmonary IR compared to the IR group, the CPB or the sham group.…”