Control of the Respiratory Cycle in Conscious Humans
There is no simple model for control of breathing in man. There are a number of degrees of freedom in the respiratory cycle. In inspiration, these include tidal volume (VTI), inspiratory time (TI) and mean inspiratory flow (MIF or VTI/TI), and in expiration, expiratory time (TE). We have developed a new technique to clamp and vary these variables individually or in combination to determine the strength of the mechanisms limiting change of each variable, and the hierarchy of control between variables. Subjects breathed into and from an open circuit via a mouthpiece and pneumotachograph and variables were measured breath-by-breath on-line by computer. Subjects coincided two bleeps of different pitches activated by the computer, one triggered at a fixed VTI and one at a fixed time after the start of inspiration (i.e. TI, expiration being initiated at this point. The threshold for each bleep could be varied from the keyboard without the subjects’ knowledge and were slowly applied to reduce subject awareness of the induced change. End-tidal PCO2 (PET,CO2) was held constant by manipulation of the inspired gas. We performed 4 sets of experiments in various combinations of 17 normal subjects in mild hyperoxia at a constant PET,CO2 slightly above resting. Each lasted 3/4–1 hour. The first experiment examined the range over which VTI and MIF could be increased and decreased by changing the threshold for the VTI bleep in 50–100 ml steps every 3 minutes at constant TE Subjects tracked the bleeps without difficulty as VTI increased by 500 ml but were not able to reduce VTI by more than 20 ml below the resting value, associated with a reduction in MIF of 12%. In a second series of experiments, TI was changed by ñ 800 msec at constant VTI using a similar technique; no difficulty was experienced in either direction, TI changing from, on average, 1.48 to 2.91 sec. In a third series of experiments, VT, and TI were reduced together from starting values at inspired PCO2 of 1, 3 and 5% to keep MIF constant while reducing VTI. At each level of chemical drive, VTI overshot the bleeps and could not be reduced below the free breathing resting value. These experiments show that timing can be changed over a wide range, that VTI and MIF can increase without difficulty, but that it is impossible to reduce VTI by more than a small amount below the resting values as dictated by the chemical drive. In a fourth series of experiments, we studied rapid shallow breathing without feedback control at constant PET,CO2 in 4 subjects. VTI fell without difficulty for prolonged periods to about 1/2 resting but end-expiratory volume as measured by a respiratory inductive plethysmograph increased to keep peak absolute tidal volume constant. In summary, these results suggest that in conscious humans, the major role of the control mechanism is to prevent a fall of tidal volume below that dictated by the chemical drive, presumably to ensure the maintenance of metabolic requirements. Mechanisms controlling timing are of lesser importance, consistent with the needs for non-metabolic functions of breathing such as speech. When VTI is forced to decrease by a programmed manoeuvre such as panting, end-expiratory volume increases to keep absolute volume constant.