Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans

Elevating core temperature at rest causes increases in minute ventilation (V̇e), which lead to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4 ± 2.0 mmHg) to the end of heating (30.5 ± 6.3 mmHg) (P = 0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8 ± 1.5 mmHg) and end (40.9 ± 2.7 mmHg) of heating (P = 1.00). The sensitivity to rising Tes (i.e., slope of the Tes − V̇E relation) did not differ between the Control and CO2-breathing trials (37.1 ± 43.1 vs. 16.5 ± 11.1 l·min−1·°C−1, P = 0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P < 0.01), despite the absence of hyperventilation-induced hypocapnia. CO2 breathing increased MCAV relative to Control at the end of heating (P = 0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia and that most of the decrease in cerebral blood flow occurs independently of hypocapnia

Effects of CO2 on ventilatory and cerebrovascular responses during passive heating in humans

Effects of CO2 on ventilatory and cerebrovascular responses during passive heating in human

Independent and combined impact of hypoxia and acute inorganic nitrate ingestion on thermoregulatory responses to the cold

Purpose: This study assessed the impact of normobaric hypoxia and acute nitrate ingestion on shivering thermogenesis, cutaneous vascular control and thermometrics in response to cold stress. Method: Eleven male volunteers underwent passive cooling at 10°C air temperature across four conditions: 1) normoxia with placebo ingestion, 2) hypoxia (0.130 FiO2) with placebo ingestion, 3) normoxia with 13 mmol nitrate ingestion, 4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45-mins to determine heat loss, and at the point of shivering onset to determine thermogenic thermoeffector threshold. Result: Independently, hypoxia expedited shivering onset time (p = 0.05) due to a faster cooling rate as opposed to a change in central thermoeffector thresholds. Specifically, compared to normoxia, hypoxia increased skin blood flow (p = 0.02), leading to an increased core-cooling rate (p = 0.04) and delta change in rectal temperature (p = 0.03) over 45-mins, yet the same rectal temperature at shivering onset (p = 0.9). Independently, nitrate ingestion delayed shivering onset time (p = 0.01), mediated by a change in central thermoeffector thresholds, independent of changes in peripheral heat exchange. Specifically, compared to placebo ingestion, no difference was observed in skin blood flow (p = 0.5), core-cooling rate (p = 0.5) or delta change in rectal temperature (p = 0.7) over 45-mins, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. Conclusion: This data improves our understanding of how hypoxia and nitric oxide modulate cold thermoregulation

Reply to Parkes: Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans

Reply to Parkes: Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated human

The nitric oxide dependence of cutaneous microvascular function to independent and combined hypoxic cold exposure

Hypoxic modulation of nitric oxide (NO) production pathways in the cutaneous microvasculature and its interaction with cold-induced reflex vasoconstriction, independent of local cooling, has yet to be identified. This study assessed the contribution of NO to non-glabrous microvasculature perfusion during hypoxia and whole-body cooling with concomitant inhibition of NO synthase (NOS; via L-NAME) and the nitrite reductase, xanthine oxidase (via allopurinol), two primary sources of NO production. Thirteen volunteers were exposed to independent and combined cooling via water perfused suit (5ºC) and normobaric hypoxia (FiO2, 0.109 ± 0.002). Cutaneous vascular conductance (CVC) was assessed across four sites with intradermal microdialysis perfusion of 1) Lactated Ringers solution (control), 2) 20 mmol L-NAME 3) 10 µmol allopurinol, or 4) combined L-NAME/allopurinol. Effects and interactions were assessed via 4-way repeated measures ANOVA. Independently, L-NAME reduced (43%, p < 0.001), while allopurinol did not alter CVC (p = 0.5). Cooling decreased CVC (p = 0.001) and the reduction in CVC was consistent across perfusates (~30%, p = 0.9). Hypoxia increased CVC (16%, p = 0.01), with this effect abolished by L-NAME infusion (p = 0.04). Cold-induced vasoconstriction was blunted by hypoxia, yet importantly hypoxia increased CVC to a similar extent (39% at the Ringer site) irrespective of environmental temperature, thus no interaction was observed between cold and hypoxia (p = 0.1). L-NAME restored vasoconstriction during combined cold-hypoxia (p = 0.01). This investigation suggests that reflex cold-induced cutaneous vasoconstriction acts independently of NO suppression, while hypoxia-induced cutaneous vasodilatation is dependent on NOS derived NO production

Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P3-] and [NO2-] in the skin interstitial fluid and plasma (all P3-] from baseline and 155±190 vs. 217±204 nM for △[NO2-] from baseline at 3 h post BR ingestion, both P≤0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid. </p