The most dramatic demonstration that breath-hold duration is not simply dependent on blood gas pressures comes from measuring the effect at breakpoint of breathing asphyxiating gas mixtures (i.e. mixtures whose inspiration lowers P_O2 formula and raises P_CO2 formula even further) on the ability to make successive breath-holds. This appears to be not widely known, yet was clearly described 51 years ago by Fowler (1954) and is alluded to much earlier (Hill & Flacke, 1908).
If there exists some threshold partial pressure(s) that invokes the involuntary termination of breath-holding, subjects should not be able to make a second breath-hold without first restoring blood gas pressures to normal. Fowler (1954), however, showed that at breakpoint (mean end-tidal P_CO2 formula 47 mmHg, n= 3 and mean oxygen saturation (S_O2 formula−3% of control values), allowing eight subjects eight breaths of an asphyxiating mixture (8% O2 and 7.5% CO2) enabled them immediately to perform another breath-hold for 20 s. At the breakpoint of the second breath-hold (mean P_CO2 formula 51 mmHg, n= 3 and mean S_O2 formula−10% of control values), another eight breaths of the asphyxiating gas enabled a further 20 s breath-hold (with gases at breakpoint being a mean P_CO2 formula of 52 mmHg, n= 3 and mean S_O2 formula of −12%). This was subsequently confirmed with 24 subjects (Flume et al. 1994).
Not only is the ability to undertake a second breath-hold essentially independent of blood gas levels, it is also independent of the volume or number of the intervening involuntary breath(s) (Godfrey & Campbell, 1969; Rigg et al. 1974; Flume et al. 1994, 1995). This ability also persists if performing an isovolume manoeuvre, or merely an inspiratory effort (−12 cmH2O pressure) against a closed airway (Rigg et al. 1974), and even after bilateral lung transplantation in nine subjects (Flume et al. 1996). The explanation for this ability may be that stopping the voluntary breath-hold confounds the involuntary breakpoint mechanism, so another breath-hold is always possible. Confounding might be achieved simply as a result of relaxing any tonic diaphragm activity (see section entitled Paralysis of the diaphragm).