Voluntary suppression of hyperthermia - induced hyperventilation mitigates the 1 reduction in cerebral blood flow velocity during exercise in the heat

31 Hyperthermia during prolonged exercise leads to hyperventilation, which can reduce 32 arterial CO2 pressure (PaCO2) and, in turn, cerebral blood flow (CBF) and thermoregulatory 33 response. We investigated 1) whether humans can voluntarily suppress hyperthermic 34 hyperventilation during prolonged exercise and 2) the effects of voluntary breathing control on 35 PaCO2, CBF, sweating and skin blood flow. Twelve male subjects performed two exercise trials 36 at 50% of peak oxygen uptake in the heat (37°C, 50% relative humidity) for up to 60 min. 37 Throughout the exercise, subjects breathed normally (normal-breathing trial) or they tried to 38 control their minute ventilation (respiratory frequency was timed with a metronome and target 39 tidal volumes were displayed on a monitor) to the level reached after 5 min of exercise 40 (controlled-breathing trial). Plotting ventilatory and cerebrovascular responses against 41 esophageal temperature (Tes) showed that minute ventilation increased linearly with rising Tes 42 during normal-breathing, whereas controlled-breathing attenuated the increased ventilation 43 (increase in minute ventilation from the onset of controlled-breathing: 7.4 vs. 1.6 l∙min at 44 +1.1°C Tes, P < 0.001). Normal-breathing led to decreases in estimated PaCO2 and middle 45 cerebral artery blood velocity (MCAV) with rising Tes, but controlled-breathing attenuated those 46 reductions (estimated PaCO2 3.4 vs. 0.8 mmHg; MCAV 10.4 vs. 3.9 cm∙s 1 at +1.1°C Tes, 47 P = 0.002 and 0.011, respectively). Controlled-breathing had no significant effect on chest 48 sweating or forearm vascular conductance (P = 0.67 and 0.91, respectively). Our results indicate 49 that humans can voluntarily suppress hyperthermic hyperventilation during prolonged exercise, 50 and this suppression mitigates changes in PaCO2 and CBF. 51 (248 words) 52