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Updated: Mar 31, 2026
A Model to Simulate Clinically Relevant Hypoxia in Humans
Published on: December 22, 2016
Multiscale computational modeling of the cardiopulmonary consequences of postnatal hyperoxia with implications for
Salla M Kim1,2, Filip Jezek3, Pim J A Oomen1,2,4
1Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center, University of California Irvine, Irvine, CA, USA.
Insights
Preterm birth impacts heart and lung development, increasing adult heart failure risk. In silico modeling of rat models reveals multiscale cardiopulmonary abnormalities, aiding understanding of long-term health effects.
Area of Science:
- Cardiology
- Pulmonology
- Computational Biology
- Developmental Biology
Background:
- Moderate to extreme preterm birth (<32 weeks gestation) leads to lasting cardiopulmonary deficits and increased adult heart failure risk.
- The rat hyperoxia (Hx) model mimics preterm birth's biventricular and pulmonary vascular changes, but synthesizing data across scales is difficult.
Purpose of the Study:
- To develop and validate an in silico multiscale model of biventricular and circulatory function.
- To investigate cardiopulmonary abnormalities at multiple scales in a rat model of preterm birth.
Main Methods:
- Calibrated a multiscale computational model using subject-specific biventricular pressure-volume data from hyperoxia-exposed (Hx) and normoxic (Nx) rats.
- Investigated cardiopulmonary function across cellular, myofiber, organ, and circulatory scales.
Main Results:
- The multiscale model accurately captured biventricular pressure-volume data from Hx and Nx rats.
- The model successfully simulated pulmonary vascular changes and right ventricular dilation consistent with preterm birth effects.
- The approach integrated multi-scale data, offering insights beyond experimental limitations.
Conclusions:
- Multiscale in silico modeling can effectively capture complex cardiopulmonary abnormalities resulting from preterm birth.
- This approach provides a foundational tool for understanding the long-term impacts of preterm birth on cardiovascular and pulmonary health.
- Computational modeling offers innovative avenues for exploring preterm birth consequences in preclinical models.
Abstract:
Moderate to extreme preterm birth (< 32 weeks gestation) affects cardiopulmonary structure and function and is associated with increased risk of heart failure through adulthood. The rat hyperoxia (Hx) model (term born; postnatal Hx exposure) captures biventricular changes, including at the cell and organ scale, and pulmonary vascular remodeling seen in preterm humans. However, synthesizing these measures across scales and organ systems is challenging. We hypothesized that in silico modeling of biventricular mitochondrial, myofiber, and organ-scale function plus circulatory function could capture key features of cardiopulmonary abnormalities due to preterm birth. Therefore, we calibrated a multiscale model to subject-specific biventricular pressure-volume data previously obtained from Hx rats alongside normoxic (Nx) controls to investigate the abnormalities in cardiopulmonary function at multiple scales in this animal model of human preterm birth. The calibrated model demonstrates excellent agreement with the data and captures the expected pulmonary vascular changes and right ventricular dilation seen in preterm-born children. Our multiscale modeling approach captures cardiopulmonary abnormalities across spatial scales and provides an innovative approach to explore the consequences of preterm birth beyond preclinical experimental data alone. This is a foundational step in understanding the impact of preterm birth on cardiopulmonary disease in childhood as well as adulthood.
