We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20-100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.

ABSTRACT. We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (0, tidal volume (V,), and mean airway pressure (Fa,) produced the lowest peakto-peak alveolar pressure amplitude (Pal,) and physiologic blood gas tensions. Sinusoidal volume changes were delivered through a tracheostomy by a piston pump driven by a linear motor. Tracheal pressure amplitude (P,,) was measured through a tracheal catheter and alveolar pressure amplitude was measured in a capsule glued to the right lower lobe. Paoz, Pacoz, P,,, and Pa,, were measured at the following settings: Fi02 = 0.5, frequency 2-28 Hz, V, 1-3 mL/kg (50 150% dead space) and Paw 5-15 cm H20. Many combinations of frequency and V, resulted in the same Pa02 and Paco2. Paw had a large effect on Pal, and minimal effect on blood gas tensions. In lavaged rabbits, the composite variable f X V : described the trends in Pa,, and blood gas tensions. As the product of f x V : increased, Paoz initially increased and then decreased, whereas Pacoz decreased and Pal,increased. No single combination of frequency, V, and Paw simultaneously provided the lowest Pal, and physiologic blood gas tensions. Adequate blood gas tensions and low Pa,, were o b t a i~d at frequencies less than 12 Hz, a V, of 2 mL/kg and a Pa, of 10 cm HzO. In healthy and lavaged rabbits Pao2 increased and Paco2 decreased as frequency increased at lower V,.Pao2 decreased as frequency increased at higher V, in lavaged rabbits only. Pa,, tended to be greater in lavaged rabbits. (Pediatr Res 27: 64-69,1990) Abbreviations f, frequency V,, tidal volume -Paw, mean airway pressure P,,, peak-to-peak tracheal pressure amplitude Selected effects off, V,, and paw on gas exchange and pressure amplitude have been studied previously in healthy and lung damaged animal models during HFOV. Oxygenation and ventilation have been shown to depend on frequency and V, (1, 2). Previous work indicating there is a relationship between C 0 2 elimination and the product of oscillatory frequency and Vt [VC02 = a(Qb(V,)" where a, b, c are constants] (3, 4) led us to evaluate the relationship of arterial blood gas tensions to the product f x V? (5). We observed that many combinations of frequency and V, produced equivalent blood gas tensions and that the composite variable f x V : was a good descriptor of our mean arterial blood gas tensions during HFOV in healthy rabbits. Others have found that different combinations of frequency, V, and Paw can produce equivalent blood gas tensions (3, 4) but the resultant pressure swings in the trachea and alveolus may not be equivalent. Near the resonant frequency of the respiratory system, pressure swings in the alveolus may exceed those at the airway opening during HFOV (8, 9). Allen et al. (10) reported that the ratio, Pa,,/P,,, increased as &, increased near the resonant frequency in excised rabbit lungs. Although increasing Paw has not been shown to improve gas exchange in healthy animals (1 1) it does improve oxygenat...

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.

Summary. Epidermal growth factor (EGF) causes gender-and development-specific changes in fetal lung surfactant synthesis. We hypothesized that the effects of EGF on development of surfactant synthesis are related to effects on EGF receptor (EGF-R) expression. We prepared sex-specific fetal rabbit lung organ cultures on gestational days 21 and 24 (term = 31 days) in Waymouth's medium + 10% charcoal-stripped fetal calf serum as control or with added EGF (10 ng/mL). After 3, 5, and 7 days of culture, we measured specific EGF-R binding in fetal lung plasma membrane preparations.Analysis of variance (ANOVA) revealed significant effects of fetal gender (P = 0.0003), time in culture (P = 0.01), and EGF treatment (P = 0.0003) on EGF specific binding. In control cultures from days 21 and 24 (both male and female), EGF specific binding tended to decrease with time in culture. Specific binding in EGF-treated female 21-day cultures was significantly higher than in controls, both after 5 days (184% of control, P = 0.007) and after 7 days (151% of control, P = 0.01; Bonferroni multiple comparisons) of treatment, whereas males exhibited no response to EGF treatment. As opposed to these effects in 21-day cultures, EGF had little effect on 24-day cultures. We conclude that EGF affects the expression of the EGF-R on EGF specific binding in the fetal lung. The development of surfactant synthesis in the fetal lung may be controlled by upregulation of the EGF-R.