Abstract 15181: Female Sex Hormones Are Protective of Vascular Cognitive Impairment in Aortic-Banded Mini-Swine
Introduction: The prevalence of heart failure with preserved ejection fraction (HFpEF) increases disproportionately following menopause, and is associated with systemic vascular dysfunction and accelerated cognitive decline. The purpose of this study was to examine the relationship between cerebrovascular function and cognition in intact (CON) and ovariectomized (OVX) aortic-banded (AB; model of HFpEF) mini-swine. We hypothesized that the combination of OVX and AB, reflecting postmenopausal HFpEF, would result in pathological cerebral vasoconstriction associated with vascular cognitive impairment.
Methods: Female Yucatan mini-swine were divided into 4 groups; CON (n=6), OVX (n=7), AB (n=6) and AB-OVX (n=7). OVX and AB procedures occurred at 7 and 8 mo. of age, respectively. Memory performance was tested using a spatial-holeboard task 4 mo. post-surgery. Carotid and cerebral blood flow (CBF; Doppler ultrasound) were measured in vivo during vena cava occlusion (autoregulation task) or at rest 6 mo. post-surgery, respectively. Myogenic tone and vasomotor responses to neuropeptide Y (NPY) were examined in vitro (pressurized myography) in cerebral resistance arteries. Significance is reported at P<0.05.
Results: Working and reference memory were impaired and CBF decreased in OVX animals (OVX main effect), with group differences in the AB-OVX vs. AB group. Average memory scores and CBF were positively correlated (R=0.54). Vascular resistance was increased (group main effect) and carotid blood flow decreased (group X time interaction) following vena cava occlusion in the AB-OVX group vs. CON. Vasoconstrictor responses to NPY in isolated cerebral resistance arteries were increased in AB-OVX vs. CON animals at all doses (group X dose interaction). Increased vasoconstriction to NPY was observed in the OVX and AB groups at higher doses only. Myogenic tone was similar between groups.
Conclusion: Cognitive deficits were associated with reduced CBF and increased vasoconstriction to NPY in the AB-OVX group. AB alone did not cause cerebrovascular or cognitive impairment, suggesting female sex hormones protect against developing vascular cognitive impairment in a translational model of pressure-overload HF with potential relevance to human HFpEF.
Author Disclosures: T. Olver: None. J.A. Hiemstra: None. J.C. Edwards: None. J.R. Ivey: None. P.K. Thorne: None. T.R. Schactman: None. P.J. Fadel: None. C.M. Heesch: None. M. Laughlin: None. C.A. Emter: None.
- © 2016 by American Heart Association, Inc.