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Mechanism of exercise intolerance in heart diseases predicted by a computer model of myocardial demand-supply
Lei Fan1, Yuexing Sun1, Jenny S Choy2
1Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA.
Insights
This study developed a computational model to understand how the heart
Area of Science:
- Cardiovascular Physiology
- Computational Biology
- Biomedical Engineering
Background:
- The heart's blood supply system (myocardial demand-supply) adapts to increased demand during exercise.
- Complex interactions occur between the heart muscle (myocardium) and its blood flow (coronary perfusion).
Purpose of the Study:
- To develop and utilize a computational framework simulating the closed-loop myocardial demand-supply feedback system.
- To investigate the impact of exercise on myocardial function under various physiological and pathological conditions.
Main Methods:
- A novel computational framework was created, coupling left ventricular systemic circulation and coronary perfusion regulation.
- The model simulates how myocardial workload influences coronary perfusion and vice-versa.
- The framework was calibrated with data from healthy subjects during graded exercise.
Main Results:
- The model accurately reproduced exercise-related cardiovascular features.
- Exercise led to increased myocardial blood flow but reduced maximum hyperemia, decreasing coronary flow reserve.
- Pathological conditions like coronary stenosis, myocardial inefficiency, and metabolic regulation dysfunction were simulated, showing faster exhaustion of coronary flow reserve and reduced exercise tolerance.
Conclusions:
- Coronary flow reserve deteriorates more rapidly during exercise in simulated pathological states.
- These findings suggest decreased exercise tolerance in patients with stenosis, myocardial inefficiency, or metabolic regulation dysfunction.
- The study's predictions may aid in diagnosing cardiovascular diseases.
Background And Objective:
The myocardial demand-supply feedback system plays an important role in augmenting blood supply in response to exercise-induced increased myocardial demand. During this feedback process, the myocardium and coronary blood flow interact bidirectionally at many different levels.
Methods:
To investigate these interactions, a novel computational framework that considers the closed myocardial demand-supply feedback system was developed. In the framework coupling the systemic circulation of the left ventricle and coronary perfusion with regulation, myocardial work affects coronary perfusion via flow regulation mechanisms (e.g., metabolic regulation) and myocardial-vessel interactions, whereas coronary perfusion affects myocardial contractility in a closed feedback system. The framework was calibrated based on the measurements from healthy subjects under graded exercise conditions, and then was applied to simulate the effects of graded exercise on myocardial demand-supply under different physiological and pathological conditions.
Results:
We found that the framework can recapitulate key features found during exercise in clinical and animal studies. We showed that myocardial blood flow is increased but maximum hyperemia is reduced during exercise, which led to a reduction in coronary flow reserve. For coronary stenosis and myocardial inefficiency, the model predicts that an increase in heart rate is necessary to maintain the baseline cardiac output. Correspondingly, the resting coronary flow reserve is exhausted and the range of heart rate before exhaustion of coronary flow reserve is reduced. In the presence of metabolic regulation dysfunction, the model predicts that the metabolic vasodilator signal is higher at rest, saturates faster during exercise, and as a result, causes quicker exhaustion of coronary flow reserve.
Conclusions:
Model predictions showed that the coronary flow reserve deteriorates faster during graded exercise, which in turn, suggests a decrease in exercise tolerance for patients with stenosis, myocardial inefficiency and metabolic flow regulation dysfunction. The findings in this study may have clinical implications in diagnosing cardiovascular diseases.
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