Respiration Physiology (1986) 66, 17I- 180 171 Elsevier EFFECTS OF VOLUME AND FREQUENCY OF MECHANICAL VENTILATION ON RESPIRATORY ACTIVITY IN HUMANS MURRAY D. ALTOSE, ROBERT J. CASTELE, ALFRED F. CONNORS, JR. and ANTHONY F. DIMARCO Cleveland Metropolitan General Hospital, Case Western Reserve University, Cleveland, OH 44109, U.S.A. Abstract. This study evaluated the interaction between respiratory chemical drive and non-chemical factors related to the frequency and level of thoracic displacement during mechanical ventilation in shaping respiratory activity. Ten normal subjects were artificially hyperventilated with a positive-pressure mechani- cal respirator to a baseline end-tidal Pco2 of approximately 30 Torr. Thereafter, in separate trials, the end-tidal Pco2 was increased by (a) progressively raising the concentration of CO2 in the inspired gas (FIco2) while holding tidal volume (VT) and breathing frequency (f) constant, (b) lowering f while holding VT and FIco2 constant, and (c) lowering VT while maintaining a constant fand FIco2. Initially, as the Pco2 rose above baseline levels with increases in FIco2, there was no change in inspiratory muscle activity, as measured by the peak inspiratory airway pressure, until the Pco2 reached 40 Tort. This Pco2 threshold for a change in respiratory activity was significantlyreduced when the tidal volume or frequency of mechanical ventilation was lowered. These results suggest that non-chemical drives related to the frequency and level of thoracic displacement interact with chemical stimuli in shaping respiratory activity. Breathing pattern Control of frequency Tidal volume Carbon dioxide Human Ventilation In conscious humans, non-chemical influences presumably involving feedback from airway, lung or chest wall mechanoreceptors contribute to the compensatory increases in respiratory activity during ventilatory loading (Kryger et al., 1975; Altose et al., 1976) and are responsible for the adjustments in respiratory output when the operating lengths of the muscles of inspiration are altered (Reid etal., 1985). Non-chemical neural regulation is also considered to be an important determinant of the level and pattern of ventilation during quiet breathing (Homma etaL, 1978; Easton etal., 1985). The purpose of the present study was to evaluate the interaction between respiratory chemi- Accepted for publication 18 July 1986 0034-5687/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)