Mechanisms regulating cerebral perfusion during running exercise: Influence of foot strike-induced pulsatility oscillations, CO2 reactivity and BP.

During running, cerebral blood flow (CBF) does not exhibit the inverted-U response observed during cycling; instead, CBF increases up to maximal exercise, despite reductions in end-tidal CO2 ( E T C O 2 ). The mechanism(s) driving this divergent response are unknown but may relate to foot strike-induced pulsatility oscillations and/or reductions in cerebrovascular CO2 reactivity (CVR). We assessed middle cerebral artery blood velocity (MCAv), E T C O 2 and MCAv pulsatility variability during an incremental running test (n = 43) and fixed workload exercise under two conditions (n = 17): (1) free running and (2) diastolic stepping, where the foot-strike was synced to the diastolic phase of the cardiac cycle. CVR was assessed (n = 12) at rest and during running. Young, healthy males and females exhibited progressive increases in the MCAv mean during incremental running (Females, Rest: 49.9 ± 11.3 cm s-1, V ̇ O 2 max : 65.7 ± 11.7 cm s-1; Males, Rest: 45.9 ± 10.8 cm s-1, V ̇ O 2 max : 67.1 ± 13.0 cm s-1; ANOVA P < 0.0001) despite reductions in E T C O 2 at higher intensities (Females, Rest: 36.41 ± 5.1 mmHg, V ̇ O 2 max : 28.2 ± 5.1 mmHg; Males, Rest: 38.6 ± 4.5 mmHg; V ̇ O 2 max : 32.5 ± 9.0 mmHg; ANOVA P < 0.0001). Diastolic stepping removed pulsatility oscillations, reducing MCAv pulsatility variability (0.14 ± 0.04 mmHg), compared with free running (0.29 ± 0.09 mmHg, P < 0.0001). However, the MCAv mean was not different (56.1 ± 8.1 cm s-1 vs. 58.0 ± 8.7 cm s-1; P = 0.211). CVR to hypocapnia decreased from rest to running (-0.79 ± 0.44 vs. -0.19 ± 0.50 cm s-1 mmHg-1; P = 0.006). Additional experiments found that hypocapnic CVR progressively decreased with increasing exercise intensity (ANOVA P = 0.0065), related to the increase in arterial pressure, but was similar during running and cycling when arterial pressure was matched (P = 0.999). These findings demonstrate that the CBF response during intense exercise is related to the prevailing arterial pressure and not modality per se, likely reflecting cerebrovascular vasoconstrictor reserve. KEY POINTS: Middle cerebral artery velocity (MCAv) increases progressively during incremental running, contrasting with the inverted-U response observed during cycling. We investigated whether this divergent response was explained by foot strike-induced pulsatility oscillations or altered cerebrovascular CO2 reactivity (CVR). Removing pulsatility oscillations, by synchronizing foot-strike with the cardiac cycle, had no effect on the MCAv mean, indicating that pulsatility oscillations do not explain the continued increase in MCAv during running. In contrast, hypocapnic CVR was markedly attenuated during high-intensity running. Follow-up experiments demonstrated that hypocapnic vasoconstrictor reserve progressively declined with increasing exercise intensity and was related to the increase in mean arterial pressure (MAP) but was similar during running and cycling when MAP was matched. These findings show that the progressive increase in MCAv during running is facilitated by a reduced responsiveness to hypocapnia, which appears related to the prevailing arterial pressure rather than modality per se. This attenuation likely reflects a reduced cerebrovascular vasoconstrictor reserve.