Alveolar pressure nonhomogeneity during small-amplitude high-frequency oscillation

In six excised canine lungs, regional alveolar pressures (PA) were measured during small-amplitude high-frequency oscillations applied at the airway opening. Both the regional distribution of PA's and their relationship to pressure excursions at the airway opening (Pao) were assessed in terms of amplitude and phase. PA was sampled in several capsules glued to the pleural surface and communicating with alveolar gas via pleural punctures. Pao and PA were measured over the frequency (f) range 1-60 Hz, at transpulmonary pressures (PL) of 5, 10, and 25 cmH2O. The amplitude of PA excursions substantially exceeded Pao excursions at frequencies near the resonant frequency. At resonance the ratio [PA/Pao] was 1.9, 2.9, and 4.8 at PL's of 5, 10, and 25 cmH2O, respectively. Both spatial homogeneity and temporal synchrony of PA's between sampled lung regions decreased with f and increased with PL. Interregional variability of airway impedance [(Pao - PA)/Vao] and tissue impedance (PA/Vao) tended to be larger than differences due to changing PL but not as large as between-dog variability. These data define the baseline nonhomogeneity of the normal canine lung and also suggest that there may be some advantage in applying high-frequency ventilation at frequencies at least as high as lung resonant frequency.     

Parenchymal interdependence and airway response to methacholine in excised dog lobes

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.     

Lung mechanics following aspiration of 0.1 N hydrochloric acid

Pressure-volume curves were obtained from excised left lungs of goats at 4, 24, and 48 h after tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Air total lung capacity (TLC) at transpulmonary pressure (PL) = 35 cmH2O was 38.8 ml/kg body weight before acid, and was reduced sharply to 21.1 at 4 h, then increased to 25.6 at 24 h and 32.1 at 48 h. Excess extravascular lung water (EVLW) could account for only part of the volume reductions. Specific compliance ratio of transpulmonary pressure to total lung capacity (CL/TLC) between PL of 5 and 0 cmH2O was reduced from 0.074/cmH2O to 0.050, 0.048, and 0.053/cmH2O, respectively. Saline TLC (PL = 10 cmH2O) changed from 44.8 to 32.4, 34.3, and 45.4 ml/kg, respectively, but CL/TLC did not, suggesting airway obstruction. After injury, trapped volume at PL = 0 increased from 24.9 to 29.2, 43.3, and 37.3% TLC with air, and from 20.3 to 38.5, 33.1, and 28.5%, respectively, with saline. Air volume at a PL = 10 cmH2O on deflation fell from 82.0 to 72.1% TLC at 4 h, but was near control at 24 and 48 h. The reduction in ventilated volume was not reflected in proportionately increased shunt; therefore, some compensatory vasoconstriction must have occurred. We suggest that in affected regions increased surface forces, increased EVLW, and airway obstruction caused reductions of lung volume.     

Mechanical properties of small airways in excised pony lungs.

We evaluated the pressure-flow relationships in collaterally ventilating segments of excised pony lungs by infusing N2, He, Ne, or SF6 at known flows (V) through a catheter wedged in a peripheral airway. Measurements were made at segment- (Ps) to-airway opening (Pao) pressure differentials of 3-15 cmH2O when the lungs were held at transpulmonary pressures of 5, 10, and 15 cmH2O. The data were analyzed both by calculating collateral resistance (Ps-Pao/V) and by constructing Moody-type plots of normalized pressure drop [(Ps-Pao)/(1/2 rho U2, where rho is density and U is velocity)] against Reynolds number to assess the pattern of flow through the segment and the change in dimension of the flow channels as Ps and Pao were changed. The interpretations from these analyses were compared with radiographic measurements of the diameters of small airways within the collaterally ventilating lung segment at similar pressures. Collateral resistance increased as Ps-Pao increased at high Reynolds numbers, i.e., high flows or dense gas (SF6). Analysis of the Moody-type plots revealed that flow was density dependent at Reynolds number greater than 100, which frequently occurred when N2 was the inflow gas. The radiographic data revealed that small airway diameter increased as Ps-Pao increased at all lung volumes. In addition, at 5 cmH2O Pao, small-airway diameter was smaller for a given Ps in the nonhomogeneous case (Ps greater than Pao) than small-airway diameter for the same Ps in the homogeneous case (Ps = Pao). We interpret these data to suggest that the surrounding lung prevented the segment from expanding in the nonhomogeneous case.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preferential axial flow during high-frequency oscillations: effects of gas density

Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that regional phasic lung distension during high-frequency oscillations (HFO) is substantially and systemically heterogeneous when both frequency (f) and tidal volume (VT) are large. They hypothesized that this phenomenon was attributable to central airway geometry and preferential axial flow induced therein by the momentum flux of the inspiratory gas stream. According to that hypothesis, the observed distribution of phasic lung distension would depend on the ratio VT/VD* (where VD* is an index of anatomic dead space), independent of gas density (rho), when f is scaled in proportion to lung resonant frequency, fo. To test this hypothesis, we used the methods of Allen et al. (ibid.) to study six excised dog lungs during HFO (f = 2-32 Hz; VT = 5-80 ml) using gases of different densities. Alveolar pressure excursions (PA) were measured as rho spanned a 12-fold range using He, air, and SF6. The apex-to-base and right-to-left ratios of PA were used as indexes of regional heterogeneity of phasic lung distension. For each gas at low f, distension of the lung base was favored slightly independent of VT, but at higher f distension of the lung apex was favored when VT was small, whereas distension of the lung base was favored when VT was large. In addition, we observed substantial right-to-left differences in apical lobes during oscillation at high f not seen before.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nonlinearity and harmonic distortion of dog lungs measured by low-frequency forced oscillations

The nonlinearity of lung tissues and airways was studied in six anesthetized and paralyzed open-chest dogs by means of 0.1-Hz sinusoidal volume forcing at mean transpulmonary pressures (Ptp) of 5 and 10 cmH2O. Lung resistance (RL) and elastance (EL) were determined in a 32-fold range (15-460 ml) of tidal volume (VT), both by means of spectrum analysis at the fundamental frequency and with conventional time-domain techniques. Alveolar capsules were used to separate the tissue and airway properties. A very small amplitude dependence was found: with increasing VT, the frequency-domain estimates of RL decreased by 5.3 and 14%, whereas EL decreased by 20 and 22% at Ptp = 5 and 10 cmH2O, respectively. The VT dependences of the time-domain estimates of RL were higher: 10.5 and 20% at Ptp = 5 and 10 cmH2O, respectively, whereas EL remained the same. The airway resistance increased moderately with flow amplitude and was smaller at the higher Ptp level. Analysis of the harmonic distortions of airway opening pressure and the alveolar pressures indicated that nonlinear harmonic production is moderate even at the highest VT and that VT dependence is homogeneous throughout the tissues. In three other dogs it was demonstrated that VT dependences of RL and EL were similar in situ and in isolated lungs at both Ptp levels.     

Gas trapping in excised rabbit lungs depends on volume history and method of degassing

Trapped gas volume (Vtg) was obtained after 5 and 10 repeated inflation-deflation cycles between transpulmonary pressure (Ptp) = 0 and 30 cmH2O in 12 experimental groups of freshly excised rabbit lungs. Gas flow rate was 1.0 ml/s except in one group (0.4 ml/s). In lungs degassed by O2 absorption (Dabs), Vtg increased from an initial 12-15% total lung capacity (TLC) (1st cycle) to 40% TLC (10th cycle), whereas in vacuum-degassed lungs (Dvac) the final Vtg was almost unchanged, remaining at less than 20% TLC. However, with the slower flow rate, Vtg in Dvac became 60% TLC. Increased lung water was not found in Dabs and therefore could not account for the above difference. In lungs not degassed after excision, Vtg increased roughly in proportion to the duration of passive collapse at Ptp = 0. However, a single brief exposure to a negative airway pressure (Pao = -10 cmH2O) resulted in a greater rate of increase of Vtg than 15-min collapse. When any of the foregoing groups were vacuum degassed after 5 cycles, they then resembled the Dvac group and showed almost no increase of Vtg in successive cycles. In Dvac, negative Pao and 15-min collapse had only minor effects on increasing Vtg. Thus, at a flow rate of 1 ml/s vacuum degassing almost eliminated all tendencies to trap gas in rabbit lungs, but the tendency was more than restored at slower flows. Brief airway closure by negative tracheal pressure can markedly enhance subsequent trapping of collapsed lungs. Differences arising from degassing methods might be due to effects on bronchomotor tone or on the physical characteristics of airway lining.     

Nonhomogeneity of lung response to inhaled histamine assessed with alveolar capsules

To assess the homogeneity of airway responses to inhaled histamine we examined regional alveolar pressure excursions (PA) arising from small-amplitude oscillations applied at the airway opening (Pao). In five anesthetized and vagotomized dogs the sternum was split and the anterior right lung field exposed. PA was sampled using four capsules affixed to the right apical and middle lobes while lung impedance (ZL) and airway impedances (Zaw) were measured during conventional tidal breathing and during forced oscillations (2-60 HZ at 10 cmH2O distending pressure). During tidal breathing after exposure to aerosol histamine regional PA's could be separated into three groups by plotting Lissajous figures of PA vs. Pao: PA in phase with Pao (no looping), PA lagging Pao (moderate looping), and PA decreasing while Pao was increasing and vice versa (paradoxical looping), suggesting unresponsive, responsive, and closed pathways, respectively, between the airway opening and specific alveolar zones. During high-frequency oscillation the corresponding PA spectra were markedly different from control spectra and revealed resonant amplification, overdamped resonance, and marked attenuation, respectively. With induced bronchospasm resonant amplification of PA was damped on average. However, the more obstructed and closed pathways were protected from resonant amplification, and the more open (nonlooping) pathways were subjected to resonant amplification greater than in the control state. In spite of this markedly nonhomogeneous behavior, frequency dependence of ZL was consistent with the model by Mead (J. Appl. Physiol. 26: 670-673, 1969), which ignores nonhomogeneity of peripheral compartments. These data demonstrate that the response of airways to inhaled histamine is nonhomogeneous but that frequency dependence of ZL above 2 Hz is not sufficient to characterize this nonhomogeneity.     

Tissue viscance during induced constriction in rabbit lungs: morphological-physiological correlations.

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of transpulmonary and driving pressures on collateral gas flow in dog lungs

The effect of changing segment pressure (Ps) and airway opening pressure (Pao) on flow through a collaterally ventilating lung segment was evaluated in intact and excised dog lungs. He, N2, and SF6 were passed through the lung segment distal to a catheter wedged in a peripheral airway at driving pressures (Ps - Pao) between 0.25 and 2 cm H2O. Eight excised caudal lobes were studied at Pao = 5, 10, and 15 cm H2O. Flow was directly related to Ps - Pao and Pao and inversely related to the density of the gas. A dimensionless plot of the driving pressure normalized to a reference dynamic pressure as a function of Reynolds number (Re) indicated that flow through the segment behaved as if it were laminar at Re less than 100 and that increasing Pao increased the dimension of the pathways conducting flow as shown previously. Small changes in Ps had no effect on pathway geometry or on the pattern of flow through the segment at Pao = 10 and 15 cmH2O. At Pao = 5 cm H2O increasing segment pressure appeared to increase the dimensions of the flow pathways slightly. Similar changes in Ps - Pao had no consistent effect on flow pattern or pathway geometry in six anesthetized, paralyzed, vagotomized dogs at functional residual capacity or after widely opening the chest (Pao = 5 cm H2O). These results suggest that, at large lobe volumes, airways (including collateral pathways) are maximally dilated and therefore relatively insensitive to small changes in segment pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of flow direction on collateral ventilation in excised dog lung lobes

We determined the effect of flow direction on the relationship between driving pressure and gas flow through a collaterally ventilating lung segment in excised cranial and caudal dog lung lobes. He, N2, and SF6 were passed through the lung segment distal to a catheter wedged in a peripheral airway. Gases were pushed through the segment by raising segment pressure (Ps) relative to airway opening pressure (Pao) and pulled from the segment by ventilating the lobe with the test gas, then lowering Ps relative to Pao. Driving pressures (Ps - Pao) between 0.25 and 2 cmH2O were evaluated at Pao values of 5, 10, and 15 cmH2O. Results were similar in cranial and caudal lobes. Flow increased as Ps - Pao increased and was greatest at Pao = 15 cmH2O for the least-dense gas (He). Although flow direction was not a significant first-order effect, there was significant interaction between volume, driving pressure, and flow direction. Dimensional analysis suggested that, although flow direction had no effect at Pao = 10 and 15 cmH2O, at Pao = 5 cmH2O, raising Ps relative to Pao increased the characteristic dimension of the flow pathways, and reducing Ps relative to Pao reduced the dimension. These data suggest that at large lobe volumes, airways (including collateral pathways) within the segment are maximally dilated and the stiffness of the parenchyma prevents any significant distortion when Ps is altered. At low lobe volumes, these pathways are affected by changes in transmural pressure due to the increased airway and parenchymal compliance.     

Comparison of the shear modulus of mature and immature rabbit lungs.

Maximal airway narrowing during bronchoconstriction is greater in immature than in mature rabbits. At a given transpulmonary pressure (PL), the lung parenchyma surrounding the airway resists local deformation and provides a load that opposes airway smooth muscle shortening. We hypothesized that the force required to produce lung parenchymal deformation, quantified by the shear modulus, is lower in immature rabbit lungs. The shear modulus and the bulk modulus were measured in isolated mature (n = 8; 6 mo) and immature (n = 9; 3 wk) rabbit lungs at PL of 2, 4, 6, 8, and 10 cmH(2)O. The bulk modulus increased with increasing PL for mature and immature lungs; however, there was no significant difference between the groups. The shear modulus was lower for the immature than the mature lungs (P < 0.025), progressively increasing with increasing PL (P < 0.001) for both groups, and there was no difference between the slopes for shear modulus vs. PL for the mature and the immature lungs. The mean value of the shear modulus for mature and immature rabbit lungs at PL = 6 cmH(2)O was 4.5 vs. 3.8 cmH(2)O. We conclude that the shear modulus is less in immature than mature rabbit lungs. This small maturational difference in the shear modulus probably does not account for the greater airway narrowing in the immature lung, unless its effect is coupled with a relatively thicker and more compliant airway wall in the immature animal.     

Frequency and amplitude effects during high-frequency vibration ventilation in dogs

High-frequency external body vibration, combined with constant gas flow at the tracheal carina, was previously shown to be an effective method of ventilation in normal dogs. The effects of frequency (f) and amplitude of the vibration were investigated in the present study. Eleven anesthetized and paralyzed dogs were placed on a vibrating table (4-32 Hz). O2 was delivered near the tracheal carina at 0.51.kg-1.min-1, while mean airway pressure was kept at 2.4 +/- 0.9 cmH2O. Table vertical displacement (D) and acceleration (a), esophageal (Pes), and tracheal (Ptr) peak-to-peak pressures, and tidal volume (VT) were measured as estimates of the input amplitude applied to the animal. Steady-state arterial PCO2 (PaCO2) and arterial PO2 (PaO2) values were used to monitor overall gas exchange. Typically, eucapnia was achieved with f greater than 16 Hz, D = 1 mm, a = 1 G, Pes = Ptr = 4 +/- 2 cmH2O, and VT less than 2 ml. Inverse exponential relationships were found between PaCO2 and f, a, Pes, and Ptr (exponents: -0.69, -0.38, -0.48, and -0.54, respectively); PaCO2 decreased linearly with increased displacement or VT at a fixed frequency (17 +/- 1 Hz). PaO2 was independent of both f and D (393 +/- 78 Torr, mean +/- SD). These data demonstrate the very small VT, Ptr, and Pes associated with vibration ventilation. It is clear, however, that mechanisms other then those described for conventional ventilation and high-frequency ventilation must be evoked to explain our data. One such possible mechanism is forcing of flow oscillation between lung regions (i.e., forced pendelluft).     

Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Collateral flow resistance and time constants in dog and horse lungs

We studied collateral flow resistance in exsanguinated, excised lower lobes and accessory lobes of dog and horse lungs, respectively. A double lumen catheter obstructed a peripheral airway isolating a segment of the lobe. Oxygen flowed into the segment via a rotameter which measured flow (Vcoll) while the inner catheter recorded segment pressure (Ps). Gas delivered into the segment flowed out via collateral channels. Collateral flow resistance was calculated as (Ps - PL)/Vcoll, where PL = static transpulmonary pressure. Rcoll at PL = 20, 10, and 5 cm H2O averaged 0.24, 1.25, and 2.65 cmH2O.ml-1.s, respectively, in the dog, and 4.53, 6.00, and 12.62 cmH2O.ml-1.s in the horse. At a given PL, Rcoll measured during inflation. At constant PL, Rcoll increased with time at PL = 5 and 10 cmH2O, but was not time dependent at PL = 20 cmH2O. At constant PL, Rcoll increased at Vcoll increased. We conclude Rcoll is greater in horses than in dogs and is a function of PL, Ps - PL, and lung volume history in both species.     

Elastic moduli of lungs during postnatal development in the piglet

Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs.     

Effect of transpulmonary pressure on airway diameter and responsiveness of immature and mature rabbits.

We previously demonstrated that airway responsiveness is greater in immature than in mature rabbits; however, it is not known whether there are maturational differences in the effect of transpulmonary pressure (Ptp) on airway size and airway responsiveness. The relationship between Ptp and airway diameter was assessed in excised lungs insufflated with tantalum powder. Diameters of comparable intraparenchymal airway segments were measured from radiographs obtained at Ptp between 0 and 20 cmH(2)O. At Ptp > 8 cmH(2)O, the diameters were near maximal in both groups. With diameter normalized to its maximal value, changing Ptp between 8 and 0 cmH(2)O resulted in a greater decline of airway caliber in immature than mature airways. The increases in lung resistance (RL) in vivo at Ptp of 8, 5, and 2 cmH(2)O were measured during challenge with intravenous methacholine (MCh: 0.001-0.5 mg/kg). At Ptp of 8 cmH(2)O, both groups had very small responses to MCh and the maximal fold increases in RL did not differ (1.93 +/- 0.29 vs. 2.23 +/- 0.19). At Ptp of 5 and 2 cmH(2)O, the fold increases in RL were greater for immature than mature animals (13.19 +/- 1.81 vs. 3.89 +/- 0.37) and (17.74 +/- 2.15 vs. 4.6 +/- 0.52), respectively. We conclude that immature rabbits have greater airway distensibility and this difference may contribute to greater airway narrowing in immature compared with mature rabbits.     

Effect of a regional increase in alveolar pressure on pulmonary blood flow.

We examined whether wedging a catheter (0.5 cm OD) into a subsegmental airway in dog (n = 6) or pig lungs (n = 5) and increasing pressure in the distal lung segment affected pulmonary blood flow. Dogs and pigs were anesthetized and studied in the prone position. Pulmonary blood flow was measured by injecting radiolabeled microspheres (15 microns diam) into the right atrium when airway pressure (Pao) was 0 cmH2O and pressure in the segment distal to the wedged catheter (Ps) was 0, 5, or 15 cmH2O and when Pao = Ps = 15 cmH2O. The lungs were excised, air-dried, and sectioned. Blood flow per gram dry weight normalized to cardiac output to the right or left lung, as appropriate, was calculated for the test segment, a control segment in the opposite lung corresponding anatomically to the test segment, the remainder of the lung containing the test segment (test lung), and the remainder of the lung containing the control segment (control lung). The presence of the catheter reduced blood flow in the test segment compared with that in the control segment and in the test lung. Blood flow was not affected by increasing pressure in the test segment. We conclude that, in studies designed to measure collateral ventilation in dog lungs, the presence of the wedged catheter is likely to have a greater effect on blood flow than the increase in pressure associated with measuring collateral airway resistance.     

Effects of tonic vagal input on breathing pattern in newborn rabbits

Respiratory effects of positive and negative pressure breathing were studied in 1- and 4-day-old rabbit pups anesthetized with ketamine (50 mg/kg, im) and acepromazine (3 mg/kg, im). We recorded tidal volume (VT), tracheal pressure (Ptr), and integrated diaphragmatic EMG (DiEMG). Inspiratory (TI) and expiratory time (TE) were measured from the records of DiEMG. During breathing with increased Ptr by 1 or 2 cmH2O, VT, minute ventilation (VE), and respiratory rate (f) decreased. Changes in f relied on a TE prolongation. Neither DiEMG nor its rate of rise (DiEMGt) were affected. Except for VT decrease during positive Ptr, all other effects disappeared after vagotomy. Our results indicate that an increase in tonic vagal activity interacts with the mechanisms controlling TE and has no effect on depth and duration of inspiration. When Ptr decreased by 1 and 2 cmH2O, VE increased due to an increase in f. Increase in f relied on shortening of both TI and TE; the TE effect being more pronounced. DiEMG and DiEMGt also increased. Adverse effects of lung deflation and vagotomy strongly suggest that the respiratory reflex stimulation due to decrease in Ptr does not rely on inhibition of the slowly adapting stretch receptor activity. Therefore other excitatory vagal inputs must be responsible for this response. We propose two vagally mediated inputs: the irritant and/or the cardiac receptors.     

Air interface and elastic recoil affect vascular resistance in three zones of rabbit lungs

We examined the effect of the air interface on pulmonary vascular resistance (PVR) in zones 1, 2, and 3 by comparing pressure-flow data of air- and liquid-filled isolated rabbit lungs. Lungs were perfused with Tyrode's solution osmotically balanced with 1% albumin and 4% dextran and containing the vasodilator papaverine (0.05 mg/ml). Lung volume was varied by negative pleural pressure form 0 to -25 cmH2O. Pulmonary artery (Ppa) and venous (Ppv) pressures were fixed at various levels relative to the lung base. Alveolar pressure (PA) was always zero, and perfusate flow was measured continuously. In zone 1 Ppa was -2.5 cmH2O and Ppv was -15 cmH2O. In zone 2 Ppa was 10 cmH2O and Ppv was -5 cmH2O. In zone 3 Ppa was 15 cmH2O and Ppv was 8 cmH2O. We found that in zone 1 the interface was essential for perfusion, but in zones 2 and 3 it had much lesser effects. In general, PVR depended almost uniquely (i.e., with small hysteresis) on transpulmonary pressure, whereas a large hysteresis existed between PVR and lung volume. PVR was high in collapsed and especially in atelectatic lungs, fell sharply with moderate inflation, and within the ranges of vascular pressure studied did not rise again toward total lung capacity. These results suggest that in zone 1 the interface maintains the patency of some alveolar vessels, probably in corners. The majority of alveolar septal vessels appears to be exposed directly to PA in zones 2 and 3, because at equal transpulmonary pressure the PVR is similar in the presence or absence of an interface.