Sex Differences in Ventricular Repolarization During Trigeminal Nerve Stimulation: Insights Into QT/RR Hysteresis

Cardiac electrical repolarization, represented by the QT interval on an ECG, is a critical component of cardiac physiology. The QT interval is inversely related to heart rate (HR), shortening at higher HRs and prolonging at lower HRs. However, during diving-induced bradycardia, QT interval prolongation is delayed – a phenomenon known as QT/RR hysteresis – likely driven by simultaneous activation of sympathetic and parasympathetic pathways (i.e., autonomic conflict). Although women typically have longer QT intervals than men at comparable HRs, the studies conducted so far have primarily involved men, leaving potential sex differences in QT/RR hysteresis unexplored. Given this, we aimed to test the hypothesis that there are sex differences in the QT interval response to simulated diving induced by trigeminal nerve stimulation (TGS). Thirty-six healthy subjects (18 women, 22±2 yr) were exposed to TGS via facial cooling for 2 minutes in a semi-recumbent position following a 5-minute baseline. Beat-to-beat HR (ECG) and blood pressure (finger photoplethysmography) were continuously measured, and QT interval duration was assessed post-data recording using automatic analysis software (ECG Analysis v2.4, LabChart, ADInstruments). Two-minute TGS induced comparable bradycardia in men and women (Δ-13±1.6 beats·min -1 vs. Δ-12±1.8 beats·min -1 ; P =0.918) and similar QT interval prolongation (Δ10±2.1 ms vs. Δ11±2.8 ms; P =0.673). However, the relationship between HR reduction and QT interval prolongation was sex-dependent. Women exhibited a very strong correlation ( r =0.923; P <0.001; F =92.3) whereas men showed a moderate correlation ( r =0.581; P =0.012; F =8.1). Women also showed a lower Akaike Information Criterion (AIC=111.19 vs. AIC=127.08), indicating superior regression model when compared to men. Notably, 15 seconds after TGS onset, women showed significant bradycardia (Δ-11±2.4 beats·min - 1 ; P =0.01) and QT interval prolongation (Δ4±0.83 ms; P <0.001) compared to rest. In contrast, despite similar bradycardic response, QT interval was unaltered in men at the onset of TGS when compared to rest. Furthermore, 20 seconds after TGS, women presented a significant tachycardia (Δ12±1.7 beats·min - 1 ; P <0.001) and QT interval shortening (Δ-5±2.2 ms; P =0.04) compared to TGS period, whereas men presented no significant change in QT interval. These findings reveal sex differences in the interplay between HR and QT interval dynamics during and after TGS. Although the underlying mechanism responsible for QT/RR hysteresis is unclear, the more robust and adaptive cardiac repolarization response observed in women may probably promote a cardioprotective condition during diving, athletic events and open-water swimming. CNPq: 307764/2022-2; CAPES: 001 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.