Tidal volume and breathing frequency responses to poikilocapnic and isocapnic hypoxia in humans

Abstract

The acute response to hypoxia in humans has been reported to arise predominately from increases in tidal volume (VT) with negligible changes in breathing frequency (fB). The effect of arterial CO2 on this response has not been described. We examined the ventilatory contributions of VT and fB to the hypoxic response under both poikilocapnic (PH) and isocapnic (IH) conditions in 10 normal adults (26 ± 4 yrs, mean ± SD). During IH, PETCO2 was held constant at 37 ± 2.0 Torr (1 Torr above resting values) while PETO2 was reduced stepwise to 45 Torr using the technique of dynamic end-tidal gas forcing. During PH, PETO2 was reduced stepwise to 45 Torr while PETCO2 was uncontrolled (i.e. zero inspired CO2). Hypoxia was maintained for 20 minutes, and tests were separated by 1 hour. Peak ventilation (VE), was significantly higher during IH (49.8 ± 14.3 L·min−1) compared to PH (24.1 ± 7.7 L·min−1, P < 0.001). During IH, peak VE was mediated by increases in both VT (1.0 ± 0.4 to 2.2 ± 0.5 L, P < 0.001) and fB (14.7 ± 4.6 to 19.2 ± 4.5 breaths·min−1, P < 0.05), while during PH peak VE was mediated by increased VT (0.8 ± 0.2 to 1.5 ± 0.4 L, P < 0.01) with no change observed in fB. At the termination of both IH and PH, a significant frequency undershoot was observed (20 ± 23 %, P < 0.05 and 22 ± 22 %, P < 0.01 respectively), previously documented only in animals. These data demonstrate a role of arterial CO2 in the development of a fB response to hypoxia, though whether this is due to CO2 per se or the magnitude of peak VE remains unknown. We have also documented a significant post hypoxic frequency decline not previously reported in humans occurring during both conditions. This study was approved by the local Ethics board and supported by AHFMR, HSFA and CIHR.