Key result
Experimental PH models consistently induce early RV diastolic dysfunction, whereas non-PH models lack serial characterization.
Why the study?
Most preclinical understanding of right ventricular diastolic dysfunction derives from pulmonary hypertension models, while the extent to which non-PH experimental disease models produce distinct RV diastolic phenotypes remains unclear.
Do non-pulmonary hypertension experimental disease models produce distinct right ventricular diastolic dysfunction phenotypes compared to pulmonary hypertension-specific models in in-vivo mammalian studies?
Systematic Review
Do non-pulmonary hypertension experimental disease models produce distinct right ventricular diastolic dysfunction phenotypes compared to pulmonary hypertension-specific models in in-vivo mammalian studies?
While pulmonary hypertension animal models exhibit a consistent and well-characterized right ventricular diastolic dysfunction phenotype, non-pulmonary hypertension models have fragmented and incomplete diastolic characterization, highlighting a need for standardized serial invasive phenotyping in preclinical right heart research.
Answers are grounded in this paper and cite their sources.
Non-PH RV diastolic phenotyping remains incomplete; extends preclinical research by highlighting gaps requiring standardized serial invasive protocols.
Background Most preclinical understanding of right ventricular (RV) diastolic dysfunction derives from pulmonary hypertension (PH) models. However, 29 experimental disease models identified in a parent systematic review encompass not only PH-specific paradigms (MCT, SuHx, chronic hypoxia) but also ischaemia, metabolic injury, congenital mimics, and acute lung injury. The extent to which these non-PH models produce distinct RV diastolic phenotypes remains unclear. Purpose To systematically characterise the range and mechanistic diversity of RV diastolic dysfunction across experimental disease models, comparing PH-specific paradigms with non-PH pathological substrates. Methods A PRISMA-compliant systematic review was conducted across MEDLINE, Embase and Cochrane databases. Twenty-nine in-vivo mammalian disease models reporting invasive or imaging-based RV diastolic parameters were identified and categorised: PH-specific (MCT, SuHx, chronic hypoxia; n=21 studies) or non-PH disease (coronary ligation/MI, ARDS, ischaemia, Western diet/metabolic, TOF repair, conduction block; n=8 studies). Diastolic (RVEDP, Tau, dP/dtmin, EDPVR), systolic, mechanistic (fibrosis, hypertrophy, energetics, inflammation), and imaging domains were extracted across species (rat, mouse, dog, pig) and stratified by temporal phase. Results PH-specific models (n=21) produced a consistent diastolic signature. RVEDP was elevated from 1-4 weeks in MCT, SuHx, and hypoxia, with Tau prolongation subacutely and sustained at 1-3 months. dP/dtmin was reduced across MCT, SuHx, and MI from 1-4 weeks. EDPVR stiffening was noted subacutely. Fibrosis, hypertrophy, oxidative stress, and mitochondrial dysfunction were established by 1-3 months. RA enlargement was evident from 1-4 weeks with sustained dilatation at intermediate phases. Interventricular uncoupling was consistent from the subacute phase. Non-PH disease models (n=8) showed divergent, fragmented patterns. MI models (coronary ligation, n=3) demonstrated subacute RVEDP elevation and dP/dtmin reduction with fibrosis, but Tau data were limited to acute ischaemia. ARDS/micro-embolism models showed acute RVEDP elevation and compliance loss but lacked longitudinal follow-up. A Western diet/PAB model showed intermediate metabolic remodelling. A single TOF repair model provided the only chronic (180-day) disease data. No non-PH disease model provided serial P-V loop data. Tau was unrecorded in chronic disease models and EDPVR was not recorded at intermediate or chronic timepoints in any disease model. Conclusions PH-specific experimental models produce a well-characterised RV diastolic phenotype, but non-PH disease models (ischaemia, ARDS, metabolic, congenital) remain critically underrepresented with fragmented diastolic reporting. Dedicated investigation of disease-specific RV diastolic remodelling beyond PH, with serial invasive phenotyping, represents an explicit research priority.
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Healy et al. (2026) conducted a systematic review in Right ventricular diastolic dysfunction in experimental mammalian disease models. Non-PH experimental disease models (coronary ligation/MI, ARDS, ischaemia, Western diet/metabolic, TOF repair, conduction block) vs. PH-specific experimental models (MCT, SuHx, chronic hypoxia) was evaluated on Right ventricular diastolic parameters (RVEDP, Tau, dP/dtmin, EDPVR) and mechanistic/imaging domains. PH-specific models (n=21) showed consistent RV diastolic dysfunction from 1-4 weeks, whereas non-PH models (n=8) had fragmented patterns with 0 serial P-V loop studies.
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