OBJECTIVES

Persistent pulmonary hypertension of the newborn (PPHN) is a complex disease with poorly understood mechanisms and risk factors. Developing animal models that reflect the pathophysiological characteristics of PPHN is critical for studying its pathogenesis and treatment strategies. This study aims to analyze the applications, methodologies, and evaluation criteria of PPHN animal models through systematic literature analysis, and to provide guidelines for establishing scientific, cost-effective, and reproducible models.

METHODS

Relevant studies published until March 2023 were retrieved from Chinese databases (CNKI, Wanfang, VIP, and SinoMed) and English databases (PubMed, Web of Science, and Embase). Data were extracted on the applications, species, modeling methods and their principles, specific procedures, species and ages of animals used, and time to model establishment, and criteria for evaluating successful model establishment. A database was created and statistical analyses were performed using Excel 2021, with results presented as charts.

RESULTS

A total of 1 157 studies were identified, and 174 met the inclusion criteria. PPHN animal models were primarily used for pathophysiological and mechanistic research (47.70%). The species used including sheep, pigs, rats, cows, and mice, ranked by frequency of use. Modeling methods were categorized into 4 types: Hypoxia exposure (44.69%), prenatal ductus arteriosus (DA) constriction (41.34%), pharmacological induction (8.94%), and combined induction (hypoxia and indomethacin, 5.03%). Each method was associated with specific species and ages. Prenatal DA constriction was exclusively performed in fetal sheep. The time to model establishment varied: Hypoxia exposure typically required >3 days, prenatal DA constriction had a median of 8.5 days, and combined induction took 3 days. Criteria for evaluating successful model establishment were categorized into 5 dimensions: Anatomical structure, histological features, hemodynamic parameters, blood gas analysis, and other physiological indicators. The most common criteria were "right ventricular hypertrophy" and "significant pulmonary arterial pressure elevation".

CONCLUSIONS

Current methods for modeling PPHN in animals are diverse, each with its strengths and limitations. Researchers should select the method most suitable for their study objectives and budget. Further exploration is needed to develop scientifically robust, cost-effective, and reproducible animal models for PPHN.