Segmental pulmonary vascular remodeling in heart failure induced by chronic volume overload

Chronic volume overload due to high-output heart failure profoundly alters pulmonary hemodynamics, yet its impact on the segmental distribution of pulmonary vascular resistance (PVR) is poorly defined. We hypothesized that long-term volume overload from an aortocaval fistula (ACF) induces compensatory reductions in microvascular and venous resistance while preserving vasoregulatory responsiveness. ACF was surgically induced in 8-week-old male Sprague-Dawley rats (n = 6); sham-operated controls (n = 6) underwent the same procedure without fistula creation. Six months later, isolated perfused and ventilated lungs were studied ex vivo. Hemodynamic parameters were recorded at controlled perfusion flow (40.0 ml/min/kg BW), and pressure–flow relationships were analyzed. Pulmonary artery, venous, and double-occlusion techniques were applied to partition total PVR into arterial, capillary, and venous segments. Hypoxic ventilation, angiotensin II, and norepinephrine were used to assess vasoreactivity. At matched flow, the ACF group exhibited a significantly lower total PVR, assessed as the slope of the pressure–flow relationship (0.05 ± 0.01 vs. 0.09 ± 0.04 mmHg·min·ml - ¹·kg, P < 0.05), which was accompanied by reduced baseline perfusion pressure (6.1 ± 1.5 vs. 8.0 ± 1.4 mmHg, P = 0.05). Segmental analysis revealed a trend toward reduced arterial pressure drop (1.7 ± 1.0 vs. 2.9 ± 1.1 mmHg, P = 0.07) and marked declines in capillary (0.8 ± 0.7 vs. 3.1 ± 1.1 mmHg, P < 0.05) and venous pressure drop (0.7 ± 1.5 vs. 2.8 ± 1.2 mmHg, P < 0.05). These changes were preserved during hypoxic pulmonary vasoconstriction. Lung wet weight tended to be higher (P = 0.07), but dry weight was significantly increased in ACF lungs (0.13 ± 0.02 vs. 0.10 ± 0.01 g, P = 0.01), indicating structural remodeling. Hypoxic and angiotensin II responses were preserved, while the norepinephrine response was augmented. These findings demonstrate a robust adaptation to chronic volume overload characterized by segment-specific post-arteriolar remodeling with preserved vasoreactivity. This structural adjustment likely mitigates pulmonary capillary hydrostatic pressure, suggesting that clinical pulmonary hypertension in high-output states is driven by excessive flow and preload rather than intrinsic vascular disease. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.