PDF(Pubmed)
Abstract：
Left heart disease (LHD) is the leading cause of pulmonary hypertension (PH). Its recent growth has not been matched by the design of therapeutic agents directly targeting the disease. Effective therapies approved for pulmonary arterial hypertension (PAH) have been shown to be inefficient in patients with PH-LHD. Hence, there is a need for an animal model that would closely mimic PH-LHD in preclinical experiments. The current study describes and compares a number of rodent models of left ventricular failure and their potential to induce PH. It also evaluates whether, and to what extent, common PH models could develop LV failure. Articles were identified in the Pubmed/Medline and Web of Science online electronic databases following the PRISMA Protocol between 1992 and 2022. Quality assessment was carried out using the SYRCLE risk-of-bias tool for animal studies. Publication bias across studies using Egger\'s regression test statistic, was performed together with sensitivity analysis. A wide spectrum of protocols-135 studies and 207 interventions, was examined, including systemic hypertensive models, pressure-overload-induced HF, model of ischemic heart failure, and metabolic approaches based on high fat diet or metabolic syndrome. The most pronounced alterations in PH-related parameters were demonstrated for the common PH models, but were also seen in animals with LV failure induced by ischemic conditions, pressure overload or metabolic conditions. Models based on aortic banding, transverse aortic constriction (TAC), or with myocardial infarction (MI) caused by coronary artery ligation, demonstrated more pronounced worsening in PH due to LV failure; however, they also demonstrated poor survival, especially the ischemic-HF model. Common PH models, excluding prolonged exposure to monocrotaline, do not promote LV hypertrophy. Prolonged exposure to a high-fat diet, or a two-hit model of an obese ZSF1 rat combined with SU5416-induced pulmonary endothelial impairment (a VEGF receptor antagonist) worsened PH and impaired diastolic dysfunction. Due to the limited number of protocols, further trials are needed to confirm the utility of such approaches for modeling PH in subjects with metabolic syndrome. This would provide a clearer insight into the complexity of LHD, PH and metabolic disorders in PH-LHD, and thus accelerate the development of new therapies in clinical trials.
摘要：
左心疾病（LHD）是肺动脉高压（PH）的主要原因。它最近的增长并没有与直接靶向疾病的治疗剂的设计相匹配。已证明，已批准用于肺动脉高压（PAH）的有效疗法在PH-LHD患者中效率低下。因此，需要在临床前实验中密切模拟PH-LHD的动物模型。当前的研究描述并比较了许多左心室衰竭的啮齿动物模型及其诱发PH的潜力。它还评估是否，在多大程度上，常见的PH模型可能会导致LV故障。根据1992年至2022年的PRISMA协议，在Pubmed/Medline和WebofScience在线电子数据库中确定了文章。使用SYRCLE偏倚风险工具进行动物研究的质量评估。使用Egger回归检验统计量的研究中的发表偏差，与敏感性分析一起进行。广泛的协议-135项研究和207项干预措施，被检查,包括系统性高血压模型，压力过载引起的HF，缺血性心力衰竭模型，和基于高脂肪饮食或代谢综合征的代谢方法。对于常见的PH模型，证明了PH相关参数的最明显变化，但在缺血条件诱导的LV衰竭的动物中也观察到，压力超负荷或代谢条件。基于主动脉束带的模型，横主动脉缩窄(TAC),或冠状动脉结扎引起的心肌梗死（MI），由于左心室衰竭，PH恶化更明显；然而，他们还表现出较差的生存，尤其是缺血性HF模型。常见的PH型号，不包括长时间接触野百合碱，不促进LV肥大。长时间接触高脂肪饮食,或肥胖ZSF1大鼠合并SU5416诱导的肺内皮损伤（VEGF受体拮抗剂）的两次打击模型会使PH恶化和舒张功能障碍受损。由于协议数量有限，需要进一步的试验来证实这种方法在代谢综合征受试者中建立PH模型的实用性.这将更清楚地了解LHD的复杂性，PH-LHD中的PH和代谢紊乱，从而加速临床试验新疗法的开发。
