The jugular venous-to-arterial difference during rebreathing and end-tidal forcing: Relationship with cerebral...

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 (P_jv-a CO₂ )] and (2) rebreathing eliminates the capacity of CVR to influence the P_jv-a CO₂ 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 P_jv-a CO₂ 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 P_jv-a CO₂ 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 P_jv-a CO₂ 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 P_jv-a CO₂ 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 . KEY 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.