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Published on: October 19, 2013
Multiscale Computational Modeling of the Cardiopulmonary Consequences of Postnatal Hyperoxia with Implications for
Salla M Kim1,2, Filip Jezek3, Pim Ja Oomen1,2,4
1Cardiovascular Innovation and Research Center, University of California Irvine, Irvine, California, USA.
Insights
Preterm birth impacts heart and lung function, increasing heart failure risk. Multiscale modeling of preterm birth in rats revealed "septal bounce" as a potential marker for right ventricular dysfunction.
Area of Science:
- Cardiopulmonary physiology
- Computational biology
- Developmental origins of health and disease
Background:
- Preterm birth (<32 weeks gestation) leads to lasting cardiopulmonary dysfunction and increased adult heart failure risk.
- Rodent models exhibit biventricular and pulmonary vascular changes mirroring human preterm infants.
- Integrating multi-scale data (cellular to organ) in preterm models is complex.
Purpose of the Study:
- To develop and calibrate an in-silico multiscale model of biventricular and circulatory function.
- To investigate the impact of preterm birth on cardiopulmonary abnormalities across scales.
- To identify potential non-invasive markers of preterm-induced cardiac dysfunction.
Main Methods:
- Calibrated a multiscale computational model using subject-specific biventricular pressure-volume data from a rat model of preterm birth and normoxic controls.
- Simulated biventricular mitochondrial, myofiber, and organ-scale function, plus circulatory dynamics.
- Analyzed correlations between septal motion, pulmonary arterial resistance, and right ventricular myofiber power.
Main Results:
- The multiscale model accurately replicated experimental data, showing increased pulmonary vascular resistance and right ventricular dilation.
- Simulations predicted increased right ventricular myofiber power and a phenomenon termed "septal bounce" (rapid septal wall movement).
- Identified significant correlations between "septal bounce" characteristics and right ventricular dysfunction severity.
Conclusions:
- Multiscale in-silico modeling effectively captures cardiopulmonary abnormalities resulting from preterm birth.
- "Septal bounce" emerged as a potential non-invasive biomarker for assessing the severity of preterm-induced right ventricular dysfunction.
- This approach offers novel insights into preterm birth's long-term cardiopulmonary consequences, extending beyond experimental data.
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. Rodent models capture 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 from a hyperoxic rat model of preterm birth alongside normoxic controls to investigate the impact of preterm birth on multiscale cardiopulmonary function. The calibrated model demonstrates excellent agreement with the data and captures the expected increases in pulmonary vascular resistance and right ventricular dilation also seen in preterm born. Simulations also predict an increase in right ventricular myofiber power and rapid septal wall flattening with subsequent rapid return to normal curvature, or "septal bounce." By calibrating a multiscale model to organ-scale data, we identified correlations between septal motion, pulmonary arterial resistance, and right ventricular myofiber power, suggesting that septal bounce may be a non-invasive marker of preterm right ventricular dysfunction severity. Our multiscale modeling approach captures cardiopulmonary abnormalities across spatial scales and provides an innovative approach to explore the consequences of preterm birth beyond experimental data alone. This is a foundational step in understanding the impact of preterm birth on cardiopulmonary disease in childhood as well as adulthood.
