학술논문

Biventricular Interaction During Acute Left Ventricular Ischemia in Mice: A Combined In-Vivo and In-Silico Approach
Document Type
article
Source
Annals of Biomedical Engineering. 51(11)
Subject
Engineering
Biomedical Engineering
Heart Disease
Heart Disease - Coronary Heart Disease
Cardiovascular
Bioengineering
Mice
Animals
Heart Ventricles
Heart
Ventricular Function
Left
Coronary Vessels
Ischemia
Computational model
Parameter estimation
Myocardial infarction
Biventricular interaction
Sensitivity analysis
Multiscale modeling
Language
Abstract
Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure-volume loop data (n = 3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure-volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems-level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia.