Mechanism of exercise intolerance in heart diseases predicted by a computer model of myocardial demand‐supply feedback system

• Published in: Computer methods and programs in biomedicine Vol. 227; p. 107188
• Main Authors: Fan, Lei, Sun, Yuexing, Choy, Jenny S., Kassab, Ghassan S., Lee, Lik Chuan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2022
• Subjects: Animals; Computational modeling; Computer Simulation; Coronary Circulation - physiology; Coronary perfusion; Coronary Stenosis; Exercise; Feedback; Flow regulation; Left ventricular function; Myocardium; Coronary perfusion; Exercise; Computational modeling; Flow regulation; Left ventricular function
• ISSN: 0169-2607; 1872-7565; 1872-7565
• DOI: 10.1016/j.cmpb.2022.107188

•A novel computational model that considers the myocardial demand-supply closed-loop feedback system is developed to study mechanism of exercise intolerance in heart diseases.•Myocardial work affects coronary perfusion via flow regulation and myocardial-vessel interactions, whereas coronary perfusion affects myocardial contractility.•Coronary flow reserve for patients deteriorates faster during graded exercise, suggesting a decrease in exercise tolerance for patients with cardiovascular diseases.•Findings in this study have clinical implications in diagnosing cardiovascular diseases. 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. 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. 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. 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.