Modeling of high sodium intake effects on left ventricular hypertrophy

Highlights

• A system-level computer simulation of chronic high sodium intake effects is conducted.

• The current model couples a cardiovascular hemodynamics model and a renal system model.

• Left ventricular (LV) wall stress is modeled to compute the changes of the LV wall thickness.

• Modeling results suggest high sodium intake alters the body-fluid homeostasis and increases the LV work load and relative wall thickness.

Abstract

Many clinical studies suggest that chronic high sodium intake contributes to the development of essential hypertension and left ventricular (LV) hypertrophy. In the present study, a system-level computer model has been developed to simulate the long-term effects of increased sodium intake on the LV mechanical functions and the body-fluid homeostasis. The new model couples a cardiovascular hemodynamics function model with an explicit account of the LV wall thickness variation and a long-term renal system model. The present model is validated with published results of clinical studies. The results suggest that, with increased sodium intake, the renal system function, the plasma hormone concentrations, and the blood pressure adapt to new levels of equilibrium. The LV work output and the relative wall thickness increase due to the increase of sodium intake. The results of the present model match well with the patient data.

Introduction

Left ventricular hypertrophy (LVH), manifested by an enlargement of myocardium tissue, is a predisposing factor for many cardiovascular diseases [1]. During the past decades, numerous studies have demonstrated a strong correlation between chronic hypertension and LVH [2], [3], [4], [5]. A physiologic adaptation of the left ventricular structure to the chronic pressure loading is generally considered the main reason for hypertrophy [4], [6]. Following the Laplace׳s law, this adaptation allows the wall stress and the pumping function to remain relatively unchanged by increase in the left ventricle (LV) tissue volume and LV wall thickness [7].

As a major contributor to the prevalence of essential hypertension [8], [9], high sodium intake has been demonstrated to cause LVH by inducing chronically elevated blood pressure [10], [11], [12]. Meanwhile, some studies also suggest that high sodium intake can also contribute to LVH through a different route, independent of or in addition to the hypertensive effect [13], [14], [15], [16], [17], [18]. In patients with essential hypertension and high sodium intake, an insufficiently down-regulated Angiotensin II concentration was found to correlate with cardiac hypertrophy [19]. Animal experiments also suggest that high sodium intake facilitates the activation of the local (cardiac) renin-angiotensin system (RAS) [20], increases the synthesis of cardiac aldosterone [21], and induces higher concentration of Angiotensin II in myocardium [22]. Based on these clinical findings, sodium restriction [23] and angiotensin-converting enzyme (ACE) inhibitor [24] have been used with positive effects on the regression of LVH and therefore successfully prescribed as treatments for LVH [6].

In the present study, a computer model has been developed to link high sodium intake to LVH based upon the existing clinical evidences. A long-term renal system model developed by Karaaslan et al. [25] is adapted and used to simulate the chronic effects of high sodium intake on body-fluid homeostasis. To account for the LV pressure loading, we used an open-source hemodynamics model of human cardiovascular system, i.e. CVSim [26]. A model for the response of the LV wall thickness to the pressure overload is developed. By combining and modifying the renal system model and the CVSim model, the new model is capable of simulating both the long-term effects of body-fluid homeostasis and the detailed structural properties of the human cardiac chambers. Since clinical studies are often restricted with test subjects and other medical issues, computer modeling will be particularly helpful for an enhanced understanding of the system-level response of the LV wall thickness to high sodium intake. The details of the model will be described in the following section.