Differential vasomotor responses to isocapnic hyperoxia: cerebral versus peripheral circulation

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Key points ATP‐sensitive K+ (KATP) channels mediate hypoxia‐induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in human cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2) during hypoxia. Hypoxia‐induced increases in the anterior circulation and total cerebral perfusion were attenuated under KATP channels blockade affecting the relative changes of brain oxygen delivery. Therefore, in humans, KATP channels activation modulates the vascular tone in the anterior circulation of the brain, contributing to CBF and CDO2 responses to hypoxia. Abstract ATP‐sensitive K+ (KATP) channels mediate hypoxia‐induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2) during hypoxia in humans. Nine healthy men were exposed to 5‐min trials of normoxia and isocapnic hypoxia (IHX, 10% O2) before (BGB) and 3 h after glibenclamide ingestion (AGB). Mean arterial pressure (MAP), arterial saturation (SnormalaO2), partial pressure of oxygen (PnormalaO2) and carbon dioxide (PnormalaCO2), internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF), total (t)CBF (Doppler ultrasound) and CDO2 were quantified during the trials. IHX provoked similar reductions in SnormalaO2 and PnormalaO2, while MAP was not affected by oxygen desaturation or KATP blockade. A smaller increase in ICABF (ΔBGB: 36 ± 23 vs. ΔAGB 11 ± 18%, p = 0.019) but not in VABF (∆BGB 26 ± 21 vs. ∆AGB 27 ± 27%, p = 0.893) was observed during the hypoxic trial under KATP channels blockade. Thus, IHX‐induced increases in tCBF (∆BGB 32 ± 19 vs. ∆AGB 14 ± 13%, p = 0.012) and CDO2 relative changes (∆BGB 7 ± 13 vs. ∆AGB −6 ± 14%, p = 0.048) were attenuated during the AGB hypoxic trial. In a separate protocol, 6 healthy men (5 from protocol 1) underwent a 5‐min exposure to normoxia and IHX before and 3 h after placebo (5 mg of cornstarch) ingestion. IHX reduced SnormalaO2 and PnormalaO2, but placebo did not affect the ICABF, VABF, tCBF, or CDO2 responses. Therefore, in humans, KATP channels activation modulates vascular tone in the anterior rather than the posterior circulation of the brain, contributing to tCBF and CDO2 responses to hypoxia.

“…A heterogeneous cerebrovascular reactivity to fluctuations in

C_{normala O_{2}}

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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K_ATP channels modulate cerebral blood flow and oxygen delivery during isocapnic hypoxia in humans

Rocha

Campos

Mattos

et al. 2020

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“…Contrary to this hypothesis, we previously showed that the brain's posterior arterial network (VA) had attenuated reactivity to isocapnic hyperoxia (Mattos et al . 2020), which hypothetically suggests that the maintenance of the brainstem perfusion would neither change nor reduce CO 2 –[H + ] washout and consequently not exert further stimulation of the central chemoreceptors. Indeed, the brain's posterior arterial network showed a reduced reactivity to poikilocapnic hyperoxia compared with the anterior cerebral circulation.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species play a modulatory role in the hyperventilatory response to poikilocapnic hyperoxia in humans

Fernandes

Mattos

Campos

et al. 2021

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Key points The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2–[H+] washout‐induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia‐induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2–[H+] washout. Abstract The hypothetical mechanism for the increase in ventilation (normalV̇E) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2–[H+] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX‐evoked increase in normalV̇E, 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. normalV̇E, arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2) and CO2 (PCO2), pH, oxidant (8‐isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8‐isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8‐isoprostane and attenuated both the reduction in CBF and the HX‐induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans‐cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2, which, in turn, seems to be evoked by the...

The jugular venous‐to‐arterial PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ difference during rebreathing and end‐tidal forcing: Relationship with cerebral perfusion

Carr,

Day,

Ainslie

et al. 2023

We examined two assumptions of the modified rebreathing technique for the assessment of the ventilatory central chemoreflex (CCR) and cerebrovascular CO2 reactivity (CVR), hypothesizing: (1) that rebreathing abolishes the gradient between the partial pressures of arterial and brain tissue CO2 [measured via the surrogate jugular venous and arterial difference (Pjv‐aCO2)] and (2) rebreathing eliminates the capacity of CVR to influence the Pjv‐aCO2 difference, and thus affect CCR sensitivity. We also evaluated these variables during two separate dynamic end‐tidal forcing (ETF) protocols (termed: ETF‐1 and ETF‐2), another method of assessing CCR sensitivity and CVR. Healthy participants were included in the rebreathing (n = 9), ETF‐1 (n = 11) and ETF‐2 (n = 10) protocols and underwent radial artery and internal jugular vein (advanced to jugular bulb) catheterization to collect blood samples. Transcranial Doppler ultrasound was used to measure middle cerebral artery blood velocity (MCAv). The Pjv‐aCO2 difference was not abolished during rebreathing (6.2 ± 2.6 mmHg; P < 0.001), ETF‐1 (9.3 ± 1.5 mmHg; P < 0.001) or ETF‐2 (8.6 ± 1.4 mmHg; P < 0.001). The Pjv‐aCO2 difference did not change during the rebreathing protocol (−0.1 ± 1.2 mmHg; P = 0.83), but was reduced during the ETF‐1 (−3.9 ± 1.1 mmHg; P < 0.001) and ETF‐2 (−3.4 ± 1.2 mmHg; P = 0.001) protocols. Overall, increases in MCAv were associated with reductions in the Pjv‐aCO2 difference during ETF (−0.095 ± 0.089 mmHg cm−1 s−1; P = 0.001) but not during rebreathing (−0.028 ± 0.045 mmHg · cm−1 · s−1; P = 0.067). These findings suggest that, although the Pjv‐aCO2 is not abolished during any chemoreflex assessment technique, hyperoxic hypercapnic rebreathing is probably more appropriate to assess CCR sensitivity independent of cerebrovascular reactivity to CO2. imageKey points Modified rebreathing is a technique used to assess the ventilatory central chemoreflex and is based on the premise that the rebreathing method eliminates the difference between arterial and brain tissue . Therefore, rebreathing is assumed to isolate the ventilatory response to central chemoreflex stimulation from the influence of cerebral blood flow. We assessed these assumptions by measuring arterial and jugular venous bulb and middle cerebral artery blood velocity during modified rebreathing and compared these data against data from another test of the ventilatory central chemoreflex using hypercapnic dynamic end‐tidal forcing. The difference between arterial and jugular venous bulb remained present during both rebreathing and end‐tidal forcing tests, whereas middle cerebral artery blood velocity was associated with the difference during end‐tidal forcing but not rebreathing. These findings offer substantiating evidence that clarifies and refines the assumptions of modified rebreathing tests, enhancing interpretation of future findings.