Grant: CIHR Fellowship

Patients with heart failure with preserved ejection fraction (HFpEF) represent ~50% of all patients with heart failure and experience accelerated cognitive decline, but the mechanisms are unknown. Augmented sympathetic nerve activity (SNA) is common in HFpEF and can mediate vasoconstriction of the blood vessels supplying the brain. My pilot data demonstrate that impaired brain blood flow control may be an underlying cause of cognitive dysfunction in our mini-swine model of HFpEF. PURPOSE: to elucidate the underlying mechanisms of impaired brain blood flow control and cognition in HFpEF. HYPOTHESIS: HFpEF-induced increases in SNA mediate vasoconstriction of brain blood vessels, leading to reduced brain blood flow and cognitive decline. METHODS: quantify spatial memory and conduct in vivo experiments examining the relationship between SNA and brain blood flow in mini-swine with HFpEF. To determine the influence of SNA on brain blood flow, these experiments will be repeated in the presence of a vascular sympathetic blocker. ANTICIPATED RESULTS: HFpEF increases SNA and subsequently reduces brain blood flow and decreases spatial memory. Vascular sympathetic blockade will normalize brain blood flow in HFpEF. THERAPEUTIC DEVELOPMENT: Additional pilot data reveal that interval exercise training enhances brain blood flow and cognition in HFpEF. Thus, a secondary purpose is to elucidate the mechanisms by which exercise prevents the maladaptive changes associated with HFpEF. To determine the optimal therapeutic 'dose' of exercise, we will repeat this experiment in HFpEF+16-wk of moderate continuous or interval exercise. We anticipate that exercise reduces SNA and tonic vasoconstriction in brain blood vessels, thereby normalizing brain blood flow and cognition. These effects will be more pronounced in the interval exercise group, given its higher intensity. Restoration of a SNA may be a mechanism by which exercise improves brain blood flow and cognition in HFpEF.