Local control of pulmonary resistance and lung compliance in the canine lung.

Local control of pulmonary resistance and lung compliance was studied in the in situ left lower lobe of the canine lung. Recirculation of blood through the lobe while the Pco2 of the ventilatory gas was varied resulted in an increase in resistance and a decrease in compliance only when the pulmonary venous pH was greater than 7.42. Alternating sodium bicarbonate and lactic acid infusion while alveolar Pco2 was maintained below 5 mmHg demonstrated the dependence of the hypocapnic response on the acid-base status of the blood perfusing the respiratory airways. The increase in resistance and decrease in compliance observed at a pulmonary venous pH of 7.64 was comparable to that observed after lobar pulmonary artery occlusion. Varying degrees of hypoxia did not significantly affect bronchomotor tone, nor was the bronchoconstriction following lobar pulmonary artery occlusion affected by the hypoxia. Vagal stimulation superimposed on a stepwise increase in pulmonary venous pH from 7.32 to 7.62 resulted in an increase in resistance which paralleled the increase in resistance when pulmonary venous pH alone was increased. Compliance was not significantly affected by vagal stimulation at any level of pulmonary venous pH.     

Frequency dependence of pulmonary compliance and resistance in patients with obstructive lung disease

The frequency dependence of pulmonary compliance and resistance was investigated in 27 patients with obstructive lung disease. Compliance and resistance were determined either by the conventional zero crossing (Cdyn) and isovolume (RL) technique or by a modified Fourier analysis following a smoothing procedure (auto- and cross-correlation function) yielding an effective compliance and resistance, CL and RL. The latter technique was used to calculate CL and RL from the fundamental and third and fourth harmonics present in the flow and transpulmonary pressure signals. Three breathing frequencies were investigated: 0.5, 1, and 2 Hz. Both Cdyn and CL, calculated from the fundamental component, decreased progressively with frequency. However, Cdyn showed less frequency dependence than CL. CL calculated from the harmonics was significantly smaller than CL from the fundamental at the same breathing frequency. RL, as well as RL calculated from the fundamental, tended to increase with frequency. A decline of resistance with frequency became apparent, however, when RL from the fundamental was compared with RL obtained from the corresponding higher order harmonics. These results suggest that the frequency dependence of resistance can be masked by the usual procedure of breathing at several frequencies. Instead the measurements should be performed at a single frequency, for instance spontaneous breathing, by computing resistance from the higher order harmonics present in the breathing signals.     

Longitudinal distribution of vascular compliance in the canine lung

With an isolated perfused canine lung, the compliance of pulmonary circulation was measured and partitioned into components corresponding to alveolar and extra-alveolar compartments. When the lungs were in zone 3, changes in outflow pressure (delta Po) affected all portions of the vasculature causing a change in lung blood volume (delta V). Thus the ratio delta V/delta Po in zone 3 represented the compliance of the entire pulmonary circulation (Cp) plus that of the left atrium (Cla). When the lungs were in zone 2, changes in Po affected only the extra-alveolar vessels that were downstream from the site of critical closure in the alveolar vessels. Thus the ratio delta V/delta Po with forward flow in zone 2 represented the compliance of the venous extra-alveolar vessels (Cv) plus Cla. With reverse flow in zone 2, delta V/delta Po represented the compliance of the arterial extra-alveolar vessels (Ca). The compliance of the alveolar compartment (Calv) was calculated from the difference between Cp and the sum of Ca + Cv. When Po was 6-11 mmHg, Cp was 0.393 +/- 0.0380 (SE) ml X mmHg-1 X kg-1 with forward perfusion and 0.263 +/- 0.0206 (SE) ml X mmHg-1 X kg-1 with reverse perfusion. Calv was 79 and 68% of Cp with forward and reverse perfusion, respectively. When Po was raised to 16-21 mmHg, Cp decreased to 0.225 +/- 0.0235 (SE) ml X mmHg-1 X kg-1 and 0.183 +/- 0.0133 (SE) ml X mmHg-1 X kg-1 with forward and reverse perfusion, respectively. Calv also decreased but remained the largest contributor to Cp. We conclude that the major site of pulmonary vascular compliance in the canine lung is the alveolar compartment, with minor contributions from the arterial and venous extra-alveolar segments.     

Perialveolar interstitial resistance and compliance in isolated rat lung

We have developed a method to characterize fluid transport through the perialveolar interstitium using micropuncture techniques. In 10 experiments we established isolated perfused rat lung preparations. The lungs were initially isogravimetric at 10 cmH2O arterial pressure, 2 cmH2O venous pressure, and 5 cmH2O alveolar pressure. Perialveolar interstitial pressure was determined by micropuncture at alveolar junctions by use of the servo-null technique. Simultaneously a second micropipette was placed in an alveolar junction 20-40 microns away, and a bolus of albumin solution (3.5 g/100 ml) was injected. The resulting pressure transient was recorded for injection durations of 1 and 4 s in nonedematous lungs. The measurements were repeated after gross edema formation induced by elevated perfusion pressure. We model the interstitium as a homogeneous linearly poroelastic material and assume the initial pressure distribution due to the injection to be Gaussian. The pressure decay is inversely proportional to time, with time constant T, where T is a measure of the ratio of interstitial tissue stiffness to interstitial resistance to fluid flow. A linear regression was performed on the reciprocal of the pressure for the decaying portion of the transients to determine T. Comparing pressure transients in nonedematous and edematous lungs, we found that T was 4.0 +/- 1.4 and 1.4 +/- 0.6 s, respectively. We have shown that fluid transport through the pulmonary interstitium on a local level is sensitive to changes in interstitial stiffness and resistance. These results are consistent with the decreased stiffness and resistance in the perialveolar interstitium that accompany increased hydration.     

Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation

Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.     

Interrelations between pulmonary liquid volumes and lung compliance.

We have investigated the relative effects of lung edema and of increases in pulmonary blood volume (PBV) on lung compliance (CL), and also the effects of selective elevations of pulmonary arterial (Ppa) and left atrial (Pla) pressures on PBV and on CL, using an isolated, perfused, and ventilated rabbit lung preparation. Lung weight was continuously recorded. A step rise in Pla at constant flow caused a rapid rise in PBV accompanied by an immediate fall in CL. With maintained high vascular pressures interstitial edema accumulated with no further fall in CL. Not until 3 times the normal amount of extra-vascular fluid had accumulated did a further, secondary reduction in CL occur. When Ppa was elevated to the same level by 1) a rise in flow and 2) a rise in Pla, the latter type of experiment gave 3-5 times larger increases in PBV. Pla elevations with or without rise in Ppa (flow adjusted) gave almost the same rises in PBV. The fall in CL was related to rises in PBV regardless of how such rises were obtained. Our conclusion is that increases in PBV, but not accumulation of interstitial edema, reduced CL in this preparation.     

Measurement of pulmonary resistance and dynamic compliance with airway obstruction

We compared four algorithms by using leastsquares regression for determination of pulmonary resistance anddynamic elastance in subjects with emphysema, normal subjects, andsubjects with asthma before and after bronchoconstriction. The fourmethods evaluated include 1) asingle resistance and elastance, 2)separate resistances and elastances for each half breath,3) separate inspiratory andexpiratory resistances with a single elastance, and4) separate inspiratory andexpiratory resistances, an expiratory volume interaction term, and asingle elastance. All methods gave comparable results in normal andasthmatic subjects. We found expiratory resistance was larger thaninspiratory resistance in normal and asthmatic subjects during controlconditions, but inspiratory resistance was higher than expiratoryresistance in subjects who experienced severe bronchoconstriction inresponse to methacholine. In subjects who are flow limited,method 2 gives a higher inspiratoryresistance than would be computed by assuming that the elasticpressure-volume curve passes through the zero-flow points.Methods 1 and3 overestimate dynamic elastance andinspiratory resistance. Method 4 appears to identify flow limitation and dynamic hyperinflation andgives a good measure of inspiratory resistance and dynamic elastance.

     

Altered pulmonary epithelial permeability in canine radiation lung injury

A radioaerosol scanning technique measuring regional clearance of sodium pertechnetate (99mTcO-4) and 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) was used to assess changes in canine pulmonary epithelial permeability following lung irradiation. Doses of 2,000 cGy (11 dogs), 1,000 cGy (2 dogs), and 500 cGy (2 dogs) were given in one fraction to either the entire right hemithorax (500 cGy) or the right lower lung (1,000 and 2,000 cGy). Radioaerosol scans, chest roentgenograms, and computerized tomograms (CT) were obtained before and serially after irradiation. A dose of 2,000 cGy resulted in a decrease in regional pulmonary epithelial permeability to both 99mTcO4- and 99mTc-DTPA; both showed significant decreases from the 2nd wk postirradiation onward. In comparison, CT and chest roentgenogram did not become abnormal until 7.1 +/- 2.8 (SD) and 8.2 +/- 2.6 wk, respectively. Doses of 1,000 and 500 cGy produced reversible decreases in 99mTcO4- clearance. Lung morphology showed definite changes of radiation pneumonitis after 2,000 and 1,000 cGy but not after 500 cGy at approximately 9, 17, and 12 wk postirradiation, respectively. These results suggest that dose-dependent changes in pulmonary physiology may precede obvious structural alterations in radiation lung injury.     

Form of branching of pulmonary air pathways in the canine lung]

The degree of regularity in bronchial dichotomy has been studied in 5 corrosive preparations of the dog bronchial tree by the method of E. R. Weibel. It has been demonstrated that a high degree of regularity is specific for the dog lungs that makes 0.82 +/- 0.12 regarding small and large diameters. Approximation in distribution of bronchi having the diameter of 3--3.5 mm in 1--9 generations by means of binomial distribution gives a good result. The greatest bronchial rate with the diameter mentioned above has been registered in 5--7 generations. Theoretical data are presented to demonstrate the necessity in regularity of bronchial branching in order to maintain an optimal gaseous exchange in lungs.     

Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes

Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 +/- 16.0% (mean +/- SD) and intermediate (between 1 and 3 mm) airways 21.8 +/- 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 +/- 15.7%) and intermediate (17.6 +/- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.     

Response of slowly adapting pulmonary stretch receptors to reduced lung compliance

We examined the steady-state response of slowly adapting pulmonary stretch receptors (SAPSRs) to reduced lung compliance in open-chest cats with lungs ventilated at eupneic rate and tidal volume (VT) and with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. Transient removal of PEEP decreased compliance by approximately 30% and increased transpulmonary pressure (Ptp) by 1-2.5 cmH2O. Reduction of compliance significantly decreased SAPSR discharge in deflation and caused a small increase in discharge at the peak of inflation; it had little effect on discharge averaged over the ventilatory cycle. Increasing VT to produce a comparable increase in Ptp significantly increased peak discharge. Thus unlike rapidly adapting receptors, whose discharge is increased more effectively by reduced compliance than by increased VT, SAPSRs are stimulated by increased VT but not by reduced compliance. We speculate that the most consistent effect of reduced compliance on SAPSRs (the decrease in deflation discharge) was due to the decreased time constant for deflation in the stiffer lung. This alteration in firing may contribute to the tachypnea evoked as the lungs become stiffer.