肺动脉高压的抗炎治疗

由各种因素引起的肺动脉高压的根本问题是肺血管重构,但其发病机制尚未完全清楚.炎症反应在肺动脉高压的发病机制中扮演了重要角色已成为共识.近年来,应用多种抗炎药物疗法干预肺动脉高压取得了许多关键进展,为临床治疗提供了新的途径.本文拟就肺动脉高压发病过程中的免疫紊乱及抗炎药物治疗的临床应用及研究现状进行综述.     

肺动脉高压治疗进展

动脉型肺动脉高压是临床上的治疗难题,近年来,随着对PAH发病机制认识的深入,开发了一系列针对肺动脉高压不同发病机制的特异性药物。肺动脉高压的常规治疗包括氧疗、抗凝、利尿治疗等,钙通道阻滞剂仅应用于急性血管反应试验阳性的患者,且其药物剂量要足够大。特异性血管扩张药物包括前列环素类似物、内皮素受体拮抗剂和磷酸二酯酶抑制剂等,随着特异性血管扩张剂的开发与应用,肺动脉高压患者的预后已明显改观。     

肺动脉高压治疗新视野

随着肺动脉高压发病机制研究的突破性进展,针对不同信号通路的关键作用靶点逐渐被认识。至今已有10多种新型肺动脉高压靶向药物陆续上市,目前治疗肺动脉高压的靶向药物主要有作用于内皮素通路的药物,作用于一氧化氮通路的药物和作用于前列环素通路的药物。上述药物主要用于治疗动脉性肺动脉高压和慢性血栓栓塞性肺动脉高压,其在临床中的应用极大地改善了肺动脉高压患者的预后。     

先天性心脏病合并肺动脉高压治疗的研究进展

肺动脉高压是先天性心脏病常见的合并症,是导致先心病患者死亡的重要原因之一。近年来,随着先天性心脏病肺动脉高压发病机制的研究进展,在治疗方面取得了重要进展,从药物治疗、外科治疗和介入治疗三个方面综述目前先天性心脏病合并肺动脉高压的治疗研究进展。     

血吸虫病相关性肺动脉高压研究进展

<正>目前人们对血吸虫病相关性肺动脉高压发病机制不甚清楚;治疗上缺乏针对性用药。一些靶向治疗药物如磷酸二酯酶-5抑制剂及酪氨酸酶抑制剂价格昂贵,对那些资源匮乏的血吸虫病地区,经济上无法承受。同时治疗肺动脉高压的药物理论上在血吸虫性肺动脉高压中可使患者受益,但仍缺乏循证医学证据,其安全性、有效性、依从性及给药途径方面存在一定的限制。本文旨在描述血吸虫病相关性肺动脉高压的发病机制、治疗及预后。     

慢性血栓栓塞性肺动脉高压

慢性血栓栓塞性肺动脉高压是肺动脉高压的一大类,是一种自然预后极差的疾病,目前认为机化血栓与肺血管重塑是其发病的重要组成部分。近年来随着基础和临床研究的发展,对慢性血栓栓塞性肺动脉高压的认知有所提高。随着外科手术治疗、介入治疗和新型靶向药物的临床应用,其预后有了明显的改善。现对慢性血栓栓塞性肺动脉高压的发病机制、病理、诊断和治疗等方面进行综述。     

低氧诱导因子在肺动脉高压发病中的作用及机制

现今,肺动脉高压患病率和病死率逐年增加,疾病进程快,但目前临床上常用的治疗肺动脉高压药物只能在一定程度上缓解肺动脉高压临床症状,不能从根本上改善肺动脉高压的肺部微循环功能障碍。因此,探索肺动脉高压发病新的分子机制,寻找新的治疗靶点,是肺动脉高压研究领域亟待解决的重要问题。低氧诱导因子家族与肺动脉高压发生发展有着紧密的联...     

门脉性肺动脉高压的诊断与治疗进展

门脉性肺动脉高压是伴或不伴晚期肝病患者在门静脉高压基础上出现以肺动脉压升高和肺血管阻力增加为特点的疾病。门脉性肺动脉高压显著增加患者病死率。目前尚无明确有效的治疗药物,肝移植是唯一有效的治疗手段。本文重点介绍了门脉性肺动脉高压的流行病学、发病机制、临床表现、诊断、治疗及预后情况。     

微小RNA在肺动脉高压发病机制中的研究进展

肺动脉高压是一种致命性疾病,缺氧、炎症、遗传等各种病因导致肺血管重塑、肺动脉压力升高,最终导致右心衰竭,甚至死亡.但目前对肺动脉高压的发病机制并不清楚,尚无治愈肺动脉高压的药物.近年来,微小RNA在许多疾病病理和生理过程中发挥的作用引起了人们的关注,许多研究表明微小RNA有逆转肺血管重塑,从而治愈肺动脉高压的可能.本文就研究较多的微小RNA在肺动脉高压的发病机制,尤其是参与血管重塑的几条通路的研究进展作一综述.     

肺动脉高压发病机制中的肺血管重塑

肺动脉高压是一类临床危重的心肺血管疾病,以肺血管阻力增加、进行性肺动脉压力升高、最终导致右心衰竭,甚至死亡为临床特点。肺血管重塑在肺动脉高压的发生发展过程中扮演着关键角色,尽管近年来靶向药物治疗已经显著改善了肺动脉高压患者的预后,目前的药物主要靶向血管舒缩功能,同时有部分改善血管重塑的作用,但无法根本上逆转肺血管重塑,故患者预后依然较差。本文从遗传机制、低氧及气体分子机制、炎症和免疫异常机制以及当前的一些新机制(内皮间质转化、异常能量代谢、表观遗传调节)等方面综述肺动脉高压发病机制中肺血管重塑的研究进展,以期为肺动脉高压的治疗提供新的思路。     

Primary pulmonary hypertension--aspects of diagnosis and therapy

Primary Lung Hypertension is a serious disease of unknown cause. Various genetic, vasoconstriction, proliferation and procoagulation factor participate in etiology and pathogenesis. In establishing the diagnosis it is necessary to exclude secondary, particularly embolic cause of pulmonary hypertension. There are diseases with associated primary pulmonary hypertension. Present therapy improves symptoms of the disease, three years after the diagnosis is established, 75% of patients survive. In the therapy of primary pulmonary hypertension, the recommended drugs are calcium channel blockers, epoprostenol, oxygen therapy and anticoagulant drugs. The new, clinically tested drugs include inhalation and oral analogs of prostacyclins, endothelin receptor antagonists and phosphodiesterase blockers.     

The lupus anticoagulant, pulmonary thromboembolism, and fatal pulmonary hypertension.

A patient with a circulating lupus anticoagulant in the absence of systemic lupus erythematosus developed recurrent deep venous thromboses and pulmonary emboli. Pulmonary emboli recurred despite prolonged oral anticoagulant therapy and resulted in fatal pulmonary arterial hypertension. Extended anticoagulant therapy alone may not prevent recurrent thromboembolism in patients with a lupus anticoagulant. Pulmonary thromboembolism may be an important factor in the pathogenesis of pulmonary hypertension in patients with a lupus anticoagulant.     

炎症及NLRP3炎性小体在肺动脉高压中的作用研究进展

肺动脉高压是以肺动脉压力进行性升高为主要特征的肺血管疾病,可导致右心衰竭甚至死亡,目前尚无特效药。近年医学界发现炎症参与了肺动脉高压的发生、发展,其中NLRP3炎性小体作为启动固有免疫应答的关键炎症信号平台有望成为人们系统性认识肺动脉高压炎症性质的蛋白复合物,也可能是治疗的潜在靶点。本文就炎症及NLRP3炎性小体在肺动脉高压中的作用进行综述。     

Reversibility of primary pulmonary hypertension with vasodilator, anticoagulant and nocturnal oxygen therapy

Successful vasodilator therapy of a 19 year old woman with primary pulmonary hypertension is described. Long-term home oxygen therapy during sleep (2 1/min, 8 hours) in combination with vasodilator drugs (prazosin 2 mg and long-acting ISDN 20 mg bid) and an anticoagulant (ticlopidine 100 mg bid) brought significant reduction of pulmonary artery pressure and a rise of cardiac output 3 years later. This combination therapy may be effective in selected patients with primary pulmonary hypertension.     

Thrombotic risk factors in pulmonary hypertension.

Thrombotic lesions are consistently observed in chronic thromboembolic pulmonary hypertension (CTEPH) and frequently found in primary pulmonary hypertension (PPH). It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thrombotic risk factors in CTEPH and PPH. One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH. In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibodies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined. Antithrombin, protein C and protein S activities were measured by functional assays. Mutations of factor V and factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of phospholipid-dependent antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH, antibodies were present only in low titre whereas in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus anticoagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phospholipid-dependent antibodies but their clinical relevance appears to be different in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic pulmonary hypertension the presence of antibodies in high titre associated with lupus anticoagulant, underlines the role of thrombosis in the pathogenesis of this condition.     

Pulmonary embolism and deep vein thrombosis

Pulmonary embolism is the third most common cause of death from cardiovascular disease after heart attack and stroke. Sequelae occurring after venous thromboembolism include chronic thromboembolic pulmonary hypertension and post-thrombotic syndrome. Venous thromboembolism and atherothrombosis share common risk factors and the common pathophysiological characteristics of inflammation, hypercoagulability, and endothelial injury. Clinical probability assessment helps to identify patients with low clinical probability for whom the diagnosis of venous thromboembolism can be excluded solely with a negative result from a plasma D-dimer test. The diagnosis is usually confirmed with compression ultrasound showing deep vein thrombosis or with chest CT showing pulmonary embolism. Most patients with venous thromboembolism will respond to anticoagulation, which is the foundation of treatment. Patients with pulmonary embolism should undergo risk stratification to establish whether they will benefit from the addition of advanced treatment, such as thrombolysis or embolectomy. Several novel oral anticoagulant drugs are in development. These drugs, which could replace vitamin K antagonists and heparins in many patients, are prescribed in fixed doses and do not need any coagulation monitoring in the laboratory. Although rigorous clinical trials have reported the effectiveness and safety of pharmacological prevention with low, fixed doses of anticoagulant drugs, prophylaxis remains underused in patients admitted to hospital at moderate risk and high risk for venous thromboembolism. In this Seminar, we discuss pulmonary embolism and deep vein thrombosis of the legs.     

Pulmonary hypertension and right ventricular failure. Part II. Patients with left ventricular involvement

In a series of articles the authors discuss literature data concerning epidemiology of pulmonary hypertension, modern classification; peculiarities of its pathogenesis and treatment in various diseases and conditions. In the second part they consider peculiarities of pathogenesis of pulmonary hypertension and right ventricular failure in patients with predominant involvement of left cardiac chambers. Effects of various classes of drugs used in the treatment of left ventricular heart failure including their influence on pulmonary circulation and functional state of the right ventricle are also discussed.     

Inhalative strategies for improvement of pulmonary hemodynamics and gas exchange in sepsis and severe pulmonary hypertension

Chronic pulmonary hypertension and septic lung failure display different clinical features resulting in severe disturbances in the pulmonary circulation. In these diseases, the pulmonary bloodflow is impaired by a pathologic constriction of blood vessels that may lead to right ventricular overloading as well as serious worsening of gas exchange mainly caused by ventilation/perfusion mismatch. Various mechanisms deteriorating the vascular function may induce both an irreversible and a reversible contraction of pulmonary vessels, respectively. Two pharmacological approaches exist to reduce the vascular resistance: Reduction of the increased vascular tone by relaxation of vascular smooth muscle cells (effect of vasodilators). Inhibition of thrombus-mediated obliteration of the lung perfusion by use of anticoagulant and fibrinolytic drugs. Prevention of the structural reorganization of pulmonary vessels (vascular remodeling) by use of vasodilators with anti-inflammatory and anti-proliferative potency such as prostanoids. The systemic (intravenous or oral) application of vasodilative agents in sepsis and chronic pulmonary hypertension has, however, important side effects: Antagonism of the hypoxic pulmonary vasoconstriction aggravates the ventilation/perfusion mismatch (decrease in arterial oxygenation). Side effects of these vasodilators (systemic hypotension). The inhalative route of application is superior because of the pulmonary enrichment of the applied agent (pulmonary selectivity). Furthermore, a preferential deposition in the well-ventilated areas of the lung is achieved (intrapulmonary selectivity). Thus, the decrease in pulmonary-vascular resistance is paralleled by both optimized ventilation-perfusion matching and subsequently improved gas exchange. First clinical studies with inhaled nitric oxide and aerosolized prostacyclin have been performed in intubated and mechanically ventilated patients with septic lung failure. At present, the use of the long-acting prostacyclin analogue ilomedin for ambulant treatment of patients with chronic pulmonary hypertension is under investigation.     

抗凝药物在肺栓塞治疗中的应用进展

肺栓塞的发病率及病死率越来越高,抗凝治疗作为肺栓塞的基石疗法尤其重要,近年来,多种新型抗凝药物不断涌现,现就抗凝药物在肺栓塞治疗中的应用及进展做一综述.     

Pulmonary embolism after brain hemorrhage in a hypertensive patient: the therapeutic dilemma

Massive pulmonary embolism is a life-threatening condition to be treated with anticoagulants or even thrombolytic agents in selected cases. However, these drugs are controindicated after a recent hemorrhagic episode. We report the case of a 46-year-old patient with uncontrolled systemic hypertension who was affected by severe spontaneous cerebral hemorrhage and left hemiparesis. After some days of rehabilitation care he developed sudden dyspnea, tachycardia and hypotension secondary to bilateral pulmonary embolism. Owing to controindication to the use of thrombolytic agents, anticoagulant therapy with high-dose intravenous unfractionated heparin followed by oral warfarin was begun, with a successful and uncomplicated outcome. The therapeutic approach to similar not uncommon cases is debated and some hypotheses are made about the aetiology of pulmonary embolism in these patients.