日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Pulmonary hypertension (PH) causes significant morbidity and mortality in diverse childhood diseases. As in adult PH, pediatric PH may be a result of heart disease, respiratory disease, hepatic portal vein disease, systemic diseases as well as idiopathic or heritable forms. However, the main characteristic of pediatric PH that distinguishes it from adult PH is its association with lung development and growth. This includes prenatal and early postnatal factors as bronchopulmonary dysplasia (BPD) and congenital diaphragmatic hernia (CDH). A number of animal models have been developed and refined to demonstrate the pathological pulmonary hallmarks found in lungs from patients with pulmonary arterial hypertension (PAH), BPD, and CDH.

Although monocrotaline and chronic hypoxia models are long-established and commonly used models of PAH, the Sugen/hypoxia model, which demonstrates human PAH pathology quite well, has been widely used as a model of PAH. In modeling BPD in experimental animals, a variety of stimuli such as hyperoxia, alveolar stretch by mechanical ventilation and antenatal inflammation have been applied in rodents and larger animals. Nitorofen, a teratogen, has commonly been used to cause CDH in animals. Recently, genetic models of CDH have become available, and multiple genetic models have CDH associated with them as part of their phenotype.

Investigations using these animal models have resulted in the discovery of many important genetic and molecular contributors to PH pathogenesis. In this review, commonly used and newly devised animal models of PH are discussed to highlight the effect of basic research on clinical practice in pediatric PH.