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Cardiac and Renal Function Interactions in Heart Failure with Reduced Ejection Fraction: A Mathematical Modeling Analysis
Author(s) -
Yu Hongtao,
Hallow Melissa Karen
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.532.15
Subject(s) - ejection fraction , cardiology , heart failure , medicine , cardiac output , ventricle , cardiac function curve , stroke volume , blood pressure
Congestive heart failure is characterized by suppressed cardiac output (CO) and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload and dysfunction. It remains a challenge to understand or predict the interplay between the heart and kidneys especially when one of them is in a state of dysfunction. Mathematical modeling provides a means to investigate the acute and chronic functional feedback between the organs. In the current work, two mechanistic mathematical models of cardiac and renal function, previously reported separately, were integrated to simulate the physiological relationships between cardiac and renal function. The two models were linked as follows: 1) mean arterial pressure (MAP) and venous pressure determined from the cardiac model serve as input to the renal model, 2) sodium and water excretion in the kidney model determines extracellular fluid volume in the cardiac model, and 3) the exchange of the fluid between the blood volume (BV) and interstitial fluid volume (ISFV) through capillary membrane was considered via starling forces. By adjusting the heart contractility, arterial stiffness, and systemic resistance, the main pathophysiological features of heart failure with reduced ejection fraction (HF‐REF) could be reproduced: decreased ejection fraction, elevated and gradually increasing BV and ISFV, elevated end diastolic pressure of the left ventricle, and loss of cardiac reserve. Quantitatively, agreement with the clinical characteristics of healthy and HF‐REF subjects seemed to support the proposed cardio‐renal model in capturing the physiological features. The cardio‐renal model can also reproduce the improvements in HF‐REF function with Angiotensin‐Converting‐Enzyme inhibitor (ACEi) as reported in the SOLVD clinical trial. This model has the potential to provide insights into the mechanisms by which pharmacologic targets in the kidney alter or improve cardiovascular function in heart failure. Support or Funding Information This research was funded by AstraZeneca This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .