After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.
Dog left upper lobes (LUL) were perfused in situ via the left lower lobe artery. Lobe weight was continuously monitored. Increasing lobar flow from normal to 10 times normal had little effect on left atrial pressure, which ranged from 1 to 5 mmHg. There was a flow threshold (Qth) below which lobar weight was stable. Qth ranged from 1.1 to 1.55 l/min (mean 1.27) corresponding to four times normal LUL blood flow. Above Qth, step increases in lobar flow resulted in progressive weight gain at a constant rate that was proportional to flow. The effective pressure at the filtration site (EFP) at different flow rates was estimated from the static vascular pressure that resulted in the same rate of weight gain. From this value and from mean pulmonary arterial (PA) and left atrial (LA) pressures, we calculated resistance upstream (Rus) and downstream (Rds) from filtration site. At Qth, Rds accounted for 60% of total resistance. This fraction increased progressively with flow, reaching 83% at Q of 10 times normal. We conclude that during high pulmonary blood flow EFP is closer to PA pressure than it is to LA pressure, and that this becomes progressively more so as a function of flow. As a result, the lung accumulates water at flow rates in excess of four times normal despite a normal left atrial pressure.
Inspiratory muscle output is downregulated when the mechanical load is reduced in awake humans. It is not known whether this is related to reduction in PCO2 or to removal of load-related neural responses. To address this issue, we did Read CO2 rebreathing tests in 13 normal subjects with and without unloading and compared respiratory output at identical end-tidal PCO2 (PET(CO2)) levels. Unloading was carried out with proportional assist ventilation (flow assist = 2 cm H2O/L/s plus volume assist = 4 cm H2O/L, representing approximately 50% reduction of the normal resistance and elastance). Ventilatory output (n = 13), total pressure of respiratory muscles (Pmus, n = 8), and transdiaphragmatic pressure (Pdi, n = 5) were computed at different PET(CO2) levels. Pmus was computed from esophageal pressure (Pes) using the Campbell diagram, and Pdi was measured from the difference between gastric pressure and Pes. Unloading caused an increase in ventilation (VI) and tidal volume (VT) at all PET(CO2) levels with no significant effect on slope (VI/PET(CO2) or VT/PET(CO2)) or respiratory rate. At low PET(CO2) (50 mm Hg), Pdi and Pmus waveforms did not differ with and without unloading. At high PET(C02) (59 mm Hg), peak Pdi and Pmus decreased by only 18.8 +/- 8.3% and 13.8 +/- 9.5%, respectively (NS, p > 0.05). Using a model that allows nonlinearity in the pressure-volume relation and for intrinsic muscle properties (force-length and force-velocity relations), we estimated the expected changes in mean VT and VI when the level of assist used in this study was applied in the absence of any change in neural output response to CO2. The predicted and observed changes in VT and VI were similar. We conclude that when chemical stimuli are rigorously controlled, unloading does not result in downregulation of respiratory muscle activation.
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