Heart failure (HF) is marked by impaired ventricular function, neurohormonal activation, and volume overload. While therapies target remodeling and neurohormonal pathways, preload management remains pivotal for symptom relief and preventing decompensation. Pressure–volume (PV) loop analysis enables precise characterization of cardiac performance during acute loading changes. To define the differential hemodynamic impact of transient inferior vena cava occlusion (IVCO) versus superior vena cava occlusion (SVCO) using PV loop analysis in a large-animal model. Controlled IVCO and SVCO were performed in healthy animals to reduce preload. PV-derived indices included stroke volume (SV), cardiac output (CO), end-systolic elastance (Ees), volume-axis intercept (V₀), and preload recruitable stroke work (PRSW). IVCO, removing ~70% of venous return, produced a marked leftward PV loop shift, decreased SV and CO, and a near-zero V₀, consistent with near-complete ventricular unloading. The end-systolic pressure–volume relationship steepened, suggesting an acute compensatory inotropic response, though Ees remained unchanged, indicating preserved intrinsic contractility. In contrast, SVCO (~30% venous return) caused only modest PV loop shifts, with preserved end-diastolic volume and stable or slightly rightward V₀. Across both interventions, preload, not intrinsic contractility, accounted for changes in mechanical work and PRSW. IVCO and SVCO elicit distinct preload-dependent hemodynamic profiles. Interpretation of PV loop–derived metrics must account for dynamic loading conditions. These findings provide mechanistic insight into acute volume regulation and warrant validation in HF-specific models to inform decongestive management strategies.
