Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with chronic inflammation but the pathological mechanisms are largely unknown. Our study aimed to simultaneously profile a broad range of cytokines in the supernatant of pulmonary endarterectomy (PEA) surgical material, as well as prospectively in patients with CTEPH to investigate whether circulating cytokines are associated with haemodynamic and physical characteristics of CTEPH patients.Herein, we show that PEA specimens revealed a significant upregulation of interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-c-induced protein-10 (IP)-10, macrophage inflammatory protein (MIP)1a and RANTES compared to lung tissue from healthy controls.In prospectively collected serum, levels of IL-6, IL-8, IP-10, monokine induced by interferon-c (MIG) and MIP1a were significantly elevated in CTEPH patients compared to age-and sex-matched healthy controls. In serum of idiopathic pulmonary arterial hypertension (IPAH) patients, only IP-10 and MIG were significantly increased. In CTEPH but not in IPAH, IP-10 was negatively correlated with cardiac index, 6-min walking distance and carbon monoxide diffusion capacity. In vitro, IP-10 significantly increased migration of freshly isolated adventitial fibroblasts.Our study is the first to show that IP-10 secretion is associated with poor pulmonary haemodynamics and physical capacity in CTEPH and might be involved in the pathological mechanism of PEA tissue formation. @ERSpublications Increased circulating IP-10 associated with poor pulmonary haemodynamics and physical capacity in CTEPH patients
BackgroundChronic thromboembolic pulmonary hypertension is surgically curable by pulmonary endarterectomy (PEA). It is unclear whether PEA impacts primarily steady state right ventricular afterload (ie, pulmonary vascular resistance (PVR)) or pulsatile right ventricular afterload (ie, pulmonary arterial compliance (CPA)). Our objectives were to (1) quantify PEA specimens and measure the impact of PEA on PVR and CPA in a structure/function study and (2) analyse the effects of haemodynamic changes on long-term survival/freedom of lung transplantation in an outcome study.MethodsThrombi were laid out, weighed, photographed and measured. PVR, CPA and resistance times compliance (RC-time) were assessed at baseline, within 4 days after PEA (‘immediately postoperative’) and 1 year after PEA, in 110 consecutive patients who were followed for 34.5 (11.9; 78.3) months.ResultsLengths and numbers of PEA specimen tails were inversely correlated with immediate postoperative PVR (p<0.0001, r=−0.566; p<0.0001, r=−0.580). PVR and CPA normalised immediately postoperatively while RC-time remained unchanged. Immediate postoperative PVR was the only predictor of long-term survival/freedom of lung transplantation (p<0.0001). Patients with immediate postoperative PVR<590 dynes.s.cm−5 had better long-term outcomes than patients with PVR≥590 dynes.s.cm−5 (p<0.0001, respectively).ConclusionsPEA immediately decreased PVR and increased CPA under a constant RC-time. However, immediate postoperative PVR was the only predictor of long-term survival/freedom of lung transplantation. Our study confirms the importance of a complete, bilateral surgical endarterectomy. Low PVR measured immediately postoperative predicts excellent long-term outcome.
Pre- and postoperative ECMO bridging in patients undergoing PEA is a feasible option to stabilize patients in a critical pre- and/or postoperative situation and to improve outcome in these patients who would otherwise probably not survive the procedure.
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