Slow ventilatory dynamics after isocapnic hypoxia and voluntary hyperventilation in humans: effects of isoflurane

Short-term potentiation (STP) of breathing refers to respiratory activity that persists at termination of a primary stimulus and is not related just to the dynamics of chemoreceptors. In humans, STP is activated by brief episodes of hypoxia and voluntary hyperventilation (VHV). STP exerts a stabilizing influence on breathing pattern. To investigate the effects of a subanaesthetic concentration of isoflurane on STP, we studied recovery from mild and moderate hypoxic hyperpnoea and VHV. Experiments were performed in eight healthy volunteers. If necessary, subjects were aroused to maintain a state of wakefulness. In the hypoxic studies, a control study involved 1 min of isocapnic hypoxia (end-tidal PO2 (PE'O2 6.1) kPa) followed by sudden transition to normoxia. In the isoflurane studies, 1 min of mild hypoxia (Iso-1 study: PE'O2 6.2 kPa) and 1 min of moderate hypoxia (Iso-2 study: PE'O2 5.7 kPa) were followed by sudden transition to normoxia during inhalation of 0.1 minimum alveolar concentration (MAC) of isoflurane. PE'CO2 was maintained at 5.9 kPa. In the VHV study, ventilatory recovery from 1 min of normoxic VHV was monitored before and during inhalation of 0.1 MAC of isoflurane. Subjects performed multiple transitions in each study. In the hypoxic studies, peak ventilation after 1 min of hypoxic stimulation did not differ between treatments. The averaged responses reached normoxic baseline after 56.3 (SEM 10.7) s in the control study (n = 47 transitions), 18.0 (3.3) s in the Iso-1 study (n = 41; P < 0.05 vs control) and 15.3 (2.4) s in the Iso-2 study (n = 23; P < 0.05 vs control). In the VHV studies, VE at termination of VHV was not different from baseline after 36 s in the control study. An immediate reduction to less than baseline ventilation, lasting 24 s, was present in the isoflurane study. We believe that shortening of the time required to reach baseline in the hypoxic studies, and hypoventilation at cessation of VHV in the isoflurane studies, are related to the inability to activate STP of breathing via an effect of isoflurane on respiratory neurones in the brain stem. Increasing the stimulus intensity during isoflurane inhalation (Iso-2 study) did not (re)-activate STP.