When pregnancy tests the heart: voluntary wheel running attenuates HFHS-associated postpartum hemodynamic dysfunction.

Pregnancy and lactation increase cardiovascular demand and may unmask postpartum cardiac vulnerability under metabolic stress. We tested whether exposure to a high-fat/high-sucrose (HFHS) diet from premating through lactation induces postpartum hemodynamic dysfunction with preserved ejection fraction (EF) and whether voluntary wheel running mitigates these alterations. Virgin C57BL/6J female mice were assigned to control sedentary (CS), HFHS sedentary (HS), or HFHS with voluntary wheel running across the reproductive window. Left ventricular (LV) pressure-volume (P-V) analysis was performed 6-9 days after weaning at baseline and during dobutamine challenge to assess β-adrenergic reserve. Despite preserved EF, HS dams exhibited reduced end-diastolic volume (EDV) and impaired forward performance [lower stroke volume (SV), cardiac output, and stroke work] accompanied by higher filling pressure, increased diastolic stiffness (end-diastolic elastance, Eed), impaired ventricular-arterial coupling (Ees/Ea), and reduced load-independent contractility [end-systolic elastance (Ees)]. Dobutamine increased chronotropic and inotropic indices across groups; however, HS remained lower than CS during dobutamine for SV and Ees, indicating limited capacity to augment performance under stress. In contrast, wheel running improved intrinsic contractility and maintained Ees/Ea at rest and during dobutamine without differences in body or heart weight. These findings indicate that HFHS exposure across pregnancy and lactation is associated with postpartum hemodynamic dysfunction characterized by preserved EF with impaired filling, increased diastolic stiffness, and reduced reserve; voluntary wheel running across this window mitigates key abnormalities in systolic mechanics and ventricular-arterial coupling.NEW & NOTEWORTHY HFHS exposure across pregnancy and lactation produces postpartum hemodynamic dysfunction with preserved EF, marked by higher filling pressure, increased diastolic stiffness, and impaired ventricular-arterial coupling and β-adrenergic reserve. Voluntary wheel running from premating through lactation improves intrinsic contractility and preserves coupling during dobutamine challenge.