Acute isometric handgrip exercise does not improve cognitive performance in patients with Fontan circulation

Fontan circulation is associated with reduced cerebral blood flow and impaired cognitive performance. Isometric handgrip (IHG) exercise has been shown to improve cognitive performance, possibly by augmenting cerebral perfusion. However, such effects have only been observed in limited samples of healthy populations. Further, the role of exercise intensity in modulating these responses has not been studied. Therefore, we tested the hypothesis that acute IHG exercise will increase the neurovascular coupling response to a cognitive task as well as cognitive performance in an intensity-dependent manner in patients with Fontan circulation and healthy control groups. Blood pressure (finger cuff photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler), end-tidal CO 2 (ETCO 2 , respiratory gas analyzer), and cognitive performance (N-2 back, targets working memory) were measured simultaneously following rest, low- (30% maximal voluntary contraction, 4 x 2-min contractions separated by 1 min rest periods), and high-intensity IHG (80% maximal voluntary contraction, 9 x 20-s separated by 1-min rest periods) in patients with Fontan circulation (n=5 (2f/3m), 18±3 years) and aged- and sex-matched healthy controls (n=5 (2f/3m), 18±3 years). Baseline mean arterial pressure was elevated (80±7 mmHg vs 87±10 mmHg), while MCAv (36±5 cm/s vs 23±8 cm/s), the cerebral vascular conductance index (CVCi, 0.46±0.05 cm/s/mmHg vs 0.26±0.11 cm/s/mmHg) and ETCO 2 (40±3 mmHg vs 30±4 mmHg) were lower in patients with Fontan circulation relative to healthy control participants ( P <0.0456). In response to N-2 back task, neither Δ%MCAv nor Δ%CVCi were different across IHG intensities ( P ≥0.9127). However, while the Δ%MCAv was not different between groups (P=0.8133), the Δ%CVCi was lower in patients with Fontan circulation relative to the healthy control participants (12±13% vs -19±31%, P =0.0013). The response time to the N-2 back was similar across IHG intensities and between groups ( P ≥0.2864). While N-2 back accuracy was not different across IHG intensities ( P =0.8595), it was lower in the patients with Fontan circulation relative to healthy control participants following low-intensity IHG (88±2% vs 94±4%, P =0.0373). Overall, the data indicate that cerebrovascular dilation associated with neurovascular coupling is reduced in patients with Fontan circulation, and acute IHG exercise does not enhance cognitive performance in this clinical population. Heart and Stroke Foundation of Canada, Scottish Rite Charitable Foundation of Canada This abstract was presented at the American Physiology Summit 2025 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.