Search

Objective: The perioperative outcome of lung transplantation (LTx) for patients with severe pulmonary hypertension (PH) remains poor due to the occurrence of primary graft dysfunction (PGD) from left ventricular failure. We hypothesized that tapering pretransplant use of epoprostenol rather than abrupt discontinuation after transplantation might improve perioperative outcomes., Methods: We performed 23 LTxs for patients with severe PH who received epoprostenol therapy from 2008 until 2021. In the discontinued group (n = 6), epoprostenol was discontinued after the establishment of extracorporeal circulation. In the tapered group (n = 17), epoprostenol was discontinued and resumed after reperfusion, and then gradually tapered over the following 2 weeks. We assessed survival, bleeding, blood transfusion, re-opening of the chest, oxygenation, PGD score, extracorporeal membrane oxygenation (ECMO) requirement for recovery after transplantation, and duration of mechanical ventilation., Results: The PGD score was significantly lower in the tapered group than in the discontinued group at 0 h, 24 h, and 48 h after LTx. In addition, the discontinued group required longer mechanical ventilation than the tapered group. Delayed chest closure and post-transplant ECMO use for recovery occurred significantly more frequently in the discontinued group., Conclusions: To resume and taper epoprostenol administration after reperfusion in patients with severe PH may be a valuable new strategy associated with better perioperative outcomes., (© 2021. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objective: Retrosternal adhesion after median sternotomy possibly raises the risk of cardiac injury at resternotomy. A biodegradable glue "Lydex" is composed of food additives, dextran and ε-poly (L-lysine), and the degradation speed can be controlled by the composition. In the present study, we evaluated the preventative effect of Lydex on retrosternal adhesion and the relationship between degradation speed and the progression of retrosternal fibrosis., Methods: Japanese white rabbits are subjected to median sternotomy. Lydex 1, 2 and 3 were loaded at the retrosternal space of rabbits in allocated groups before sternal closure, respectively (n = 11 for each group). Retrosternal adhesion was macroscopically evaluated after surgery. Retainment of Lydex, retrosternal fibrosis and the infiltration of macrophages are histologically evaluated, respectively., Results: All Lydex groups exhibited less retrosternal adhesion at 4 weeks after loading compared to unloaded control. The degradation speed of Lydex varied according to the compositions. Lydex with faster degradation (Lydex 2 or Lydex 3) showed lower progression of retrosternal fibrosis compared to that with slower degradation (Lydex 1) [fibrosis ratio: control vs Lydex 1 vs Lydex 2 vs Lydex 3: 0.60 ± 0.15 vs 0.18 ± 0.17 vs 0.00 ± 0.00 vs 0.00 ± 0.00, P = 0.0005 (Lydex 1 vs Lydex 2), P = 0.0005 (Lydex 1 vs Lydex 3)]. Retrosternal infiltrations of macrophages in Lydex 1 and Lydex 3 groups are not higher compared to that in unloaded control., Conclusions: The degradation speed of Lydex could be controlled according to the compositions. The degradation speed affected the progression of retrosternal fibrosis.

Objectives: Systemic inflammation evoked by cardiopulmonary bypass (CPB) leads to acute lung injury (ALI) and respiratory failure. Although recombinant human soluble thrombomodulin (rTM) consists of three domains (D1-3), is reported to attenuate systemic inflammation through the N-terminal lectin-like domain (D1), anticoagulant domain (D2) may exacerbate coagulopathy after CPB. We investigated the potential of selective D1 against CPB-mediated ALI free from anticoagulant effects using a rat CPB model., Methods: Rats were divided into three groups: control (CPB alone, n = 5), D1 (CPB + D1, n = 4), and D123 (CPB + D123, n = 6). D1 or D123 was administrated to the rats of each group before CPB establishment. Blood samples are collected before, during and after CPB. Blood coagulability was assessed by a coagulation analyzer. Lung samples are collected at 1 h after the termination of CPB for histological analyses., Results: D123 group exhibited significantly prolonged glass beads-activated clotting time with heparinase after CPB compared to that in control group, whereas no significant prolongation in control and D1 group (control vs. D1 vs. D123: 65.4 ± 9.2 vs. 65.3 ± 10.9 vs. 83.5 ± 4.6 s, p = 0.036 [control vs. D123], 0.99 [control vs. D1]) indicating the absence of anticoagulant activities of D1. Histological studies revealed less congestion, edema, inflammation, and hemorrhage in both D1 and D123 groups compared to those in control group indicating protective effects of both D1 and D123 against ALI mediated by CPB., Conclusions: N-terminal lectin-like domain of rTM may reduce the risk of ALI without anticoagulant effects.

Objective: Although surgical ventricular restoration for ischemic cardiomyopathy is expected as an alternative or bridge to heart transplantation, post-operative remodeling of left ventricle (LV) needs to be addressed. This study aimed to examine the effect of basic fibroblast growth factor (bFGF), which induces angiogenesis and tissue regeneration in ischemic myocardium, to prevent remodeling after surgical ventricular restoration (SVR) using a rat ischemic cardiomyopathy model., Methods: Four weeks after coronary artery ligation, rats were divided into two groups: rats treated with SVR alone (SVR; n = 21), and rats treated with SVR and local sustained release of bFGF using gelatin hydrogel sheet (SVR + bFGF; n = 22). Cardiac function was assessed by serial echocardiography and cardiac catheterization. Cardiac tissue sections were histologically examined for vascular density and fibrosis., Results: Higher systolic function and lower LV end-diastolic pressure (LVEDP) were observed in rats treated with SVR + bFGF (SVR vs SVR + bFGF; Ees: 0.22 ± 0.11 vs 0.33 ± 0.22 mmHg/μL, p = 0.0328; LVEDP: 12.7 ± 7.0 vs 8.5 ± 4.3 mmHg, p = 0.0230). LV area tended to be lower in rats treated with SVR + bFGF compared to rats treated with SVR alone (left-ventricular end-diastolic area: 0.66 ± 0.07 vs 0.62 ± 0.07 cm 2 , p = 0.071). Vascular density tended to be higher in rats treated with SVR + bFGF than those without bFGF (23.3 ± 8.1 vs 28.8 ± 9.5/mm 2 , p = 0.0509)., Conclusions: BFGF induced angiogenesis and attenuated remodeling after SVR which secured the efficacy of SVR in a rat ischemic cardiomyopathy model.