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

Abstract

The routine use of mechanical circulatory support during lung transplantation (LTx) is still controversial. The use of prophylactic human albumin (HA) or hypertonic sodium lactate (HSL) prime in mechanical circulatory support during LTx could prevent ischemia–reperfusion (IR) injuries and pulmonary endothelial dysfunction and thus prevent the development of pulmonary graft dysfunction. The objective was to investigate the impact of cardiopulmonary bypass (CPB) priming with HA and HSL compared to a CPB prime with Gelofusine (GF) on pulmonary endothelial dysfunction in a lung IR rat model. Rats were assigned to four groups: IR-CPB-GF group, IR-CPB-HA group, IR-CPB-HSL group and a sham group. The study of pulmonary vascular reactivity by wire myograph was the primary outcome. Glycocalyx degradation (syndecan-1 and heparan) was also assessed by ELISA and electron microscopy, systemic and pulmonary inflammation by ELISA (IL-1β, IL-10, and TNF-α) and immunohistochemistry. Clinical parameters were evaluated. We employed a CPB model with three different primings, permitting femoral–femoral assistance with left pulmonary hilum ischemia for IR. Pulmonary endothelium-dependent relaxation to acetylcholine was significantly decreased in the IR-CPB-GF group (11.9 ± 6.2%) compared to the IR-CPB-HA group (52.8 ± 5.2%, p < 0.0001), the IR-CPB-HSL group (57.7 ± 6.3%, p < 0.0001) and the sham group (80.8 ± 6.5%, p < 0.0001). We did not observe any difference between the groups concerning glycocalyx degradation, and systemic or tissular inflammation. The IR-CPB-HSL group needed more vascular filling and developed significantly more pulmonary edema than the IR-CPB-GF group and the IR-CPB-HA group. Using HA as a prime in CPB during Ltx could decrease pulmonary endothelial dysfunction’s IR-mediated effects. No effects of HA were found on inflammation.

Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy

“…Interestingly, the glycocalyx layer was better preserved when the CPB circuit was coated with heparin compared to phosphorylcholine in cardiac surgery patients [225]. In contrast, glycocalyx degradation did not differ between priming the CPB circuit with human albumin or gelofusine in rats [226]. Unfortunately, the above-mentioned studies did not investigate whether the protection of the endothelial glycocalyx reduced myocardial IRI.…”

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis

“…In addition, albumin can also reduce heme-induced hepatic sinusoidal contraction and cytotoxicity, and improve liver microcirculation and organ function by binding heme. Albumin in mouse models of pulmonary ischemia-reperfusion reduces the risk of pulmonary edema and improves endothelial dysfunction [ 88 , 89 ].…”