Background. Increased negative intrathoracic pressures are recognized to exacerbate left ventricular dysfunction in obstructive sleep-disordered breathing. Reportedly left ventricular stroke volume (LVSV) decline appeared greater than predicted by the obstruction alone. Objectives. Whether this effect is more dependent on biventricular elasticity and fluid shifts than on breathing-related transmural pressures could be inferred from a mathematical model simulation. Design. A previously validated cardiopulmonary model in healthy subjects during inspiratory loading was modified by parameter adjustments to fit its ventricular volumes output to published clinical data of decreased LVSV in obstructed breathing. Results. Reduced left ventricular end-diastolic compliance and increased central blood volume from baseline each simulated a 20% drop in LVSV whereas twice as much change was the result of increasing a mere 400？mL to the unstressed volume of systemic veins. An intermediate value was obtained by decreasing right ventricular end-diastolic compliance and higher systemic venous compliance. Conclusions. Simulations encompassing a wide range of decreased stroke volume at comparable intrathoracic pressures suggested a prominent role of decreased myocardial distensibility (possibly coupled to fluid migration) in the stroke volume fall. 1. Introduction Obstructive sleep-disordered breathing (OSB) is associated with cardiovascular comorbidities (hypertension, increased afterload, sympathetic outflow, heart failure, left ventricular (LV) dysfunction, cyclical increases in LV wall tension, increased venous return) with variable decreases in LV stroke volume (LVSV) measured mostly around 30？cmH2O of negative intrathoracic pressure (Pth) [1–16]. However, only a fraction of the magnitude of these LVSV drop was depicted by a mathematical model simulation [17], validated with the inspiratory fall in arterial pressure during spontaneous breathing at increased inspiratory loading in normal subjects over a wider Pth range (up to ？52？mmHg). Thus, although increased negative Pth in OSB (with concomitant increased LV afterload by higher LV transmural intracavitary pressure and reduced LV preload by interdependence) is recognized as an independent pathophysiological mechanism, it partially explains the larger LVSV reduction in OSB patients when compared to that simulated by inspiratory loading. Here the model simulation further explores this discrepancy by assessing the potential role of LV rigidity, end-diastolic, and end-systolic LV volumes and volume overload at different
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