Grouping | Recommendations from guidelinesa | Specific application to PAH | Justification |
---|---|---|---|
Animal subjects | Model matches age of patients to clinical setting | Adult animals included | |
 | Characterization of animal properties at baseline | RVSP or mPAP assessed at baseline | Confirmation that the model successfully establishes PAH |
 | Matching model to sex of patients in clinical setting | Both male and female animal included | Prevalence of PAH occurs in female versus males is 2:1 [31, 32] |
Outcome measurements | Matching of measure to clinical outcome | Clinically relevant outcome reported (e.g., pulmonary hemodynamics, RV remodeling, cardiac function, mortality) | Clinically relevant outcomes may increase potential generalizability to clinical setting |
 |  | Long-term follow-up (>3 weeks post-intervention) | PAH is a chronic disease; long-term assessment increases reliability of findings |
 |  | Pulmonary hemodynamics assessed by direct catheterization | Right heart catheterization is the gold standard for diagnosing PAH |
 | Assessment of multiple manifestations of disease phenotype | Study reports ≥2 types of outcome measurements (pulmonary hemodynamics, RV remodeling, cardiac function, mortality, histopathological assessment of vascular lesions) | Efficacy in multiple manifestations of PAH may increase reliability of findings |
Modeling of disease | Matching model to human manifestation | Criteria for PAH are met in disease control (mPAP >25Â mmHg; RVSP >35Â mmHg [12, 33]) | PAH is induced successfully in the model |
 | Treatment response along mechanistic pathway | A molecular or cellular mechanism of treatment is measured and reported | Ensures therapy is producing a biological effect; ensures negative effects cannot be ascribed to a lack of biological activity |
Administration of intervention | Matching timing of treatment delivery to clinical setting | Intervention is given after PAH is established (>2Â weeks in animal models) | PAH usually present with symptoms before diagnosis |
 | Matching the duration/exposure of treatment to clinical setting | Evidence of cell persistence in any animal organ | Ensures presence of cells during course of treatment |
 | Matching model to co-interventions in clinical setting | Animals are on background medical therapy for PAH (e.g., Prostacyclins endothelin receptor antagonists, PDE5 inhibitors, calcium channel blockers) | PAH patients would be on conventional pharmacotherapy |
Environment | Address confounders associated with setting, experimental setting | General anesthetic is not used during outcome measurements | Anesthetics may exert effects on cardiovascular system; patients undergo right heart catheterization under local anesthetic, echocardiography performed without anesthetics in patients |