Loading conditions rather than contractility primarily determine biventricular ejection fraction in endotoxic shock

Ejection fraction (EF) is widely used to assess cardiac function in sepsis, yet it is inherently load-dependent and may not reflect intrinsic contractility. We quantified the relative contribution of hemodynamic determinants to left (LVEF) and right ventricular EF (RVEF) in a porcine model of endotoxic shock. Twelve female pigs were instrumented with biventricular conductance catheters and studied at four stages: baseline, endotoxic shock, fluid resuscitation, and norepinephrine infusion. Six candidate determinants (effective arterial elastance (Ea), end-systolic elastance (Ees), end-diastolic volume (EDV), heart rate (HR), the time constant of isovolumic relaxation (τ), and internal flow fraction (IFF)) were evaluated using centering within clusters linear mixed models (LV: 12 animals; RV: 9 animals). Ea, EDV, and Ees were the dominant determinants of LVEF, accounting for 31%, 27%, and 19% of explained variance (combined: 77%), while HR exerted a negative effect. For RVEF, predictor importance was more evenly distributed, with EDV and Ea as the leading contributors in dominance analysis; HR was positively associated with RVEF, opposite to its LV effect. This loading-dominant hierarchy persisted when Ees was replaced by alternative load-independent indices: preload-recruitable stroke work (PRSW) and Starling contractility index (SCI). Despite substantial stage-to-stage changes in preload, afterload, and contractility, EF varied within a narrow range (LVEF 37-45%; RVEF 50-60%), reflecting offsetting changes among determinants. Within this pressure-volume framework, loading conditions rather than contractility were the primary within-animal determinants of LVEF during endotoxic shock. The RV data were consistent with a similar hierarchy, although with differing determinant profiles and greater analytical uncertainty.