Biomedical subjects

M S Ludwig

Publications and source records attributed to M S Ludwig.

53 records · Page 3Linked to original sources

PubMed1993

Comparative study of mechanical interdependence: effect of lung volume on Raw during induced constriction.

The mechanical load imposed by the parenchyma can decrease the magnitude of agonist-induced airway constriction. To examine whether variability in mechanical interdependence could account for differences in airway narrowing among different species, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in rats and guinea pigs. Direct measurements of Raw were made under baseline conditions at different levels of end-expiratory transpulmonary pressure (PL = 3-11 cmH2O). Then aerosolized MCh was delivered (128 mg/ml in rats, 8 mg/ml in guinea pigs), and measurements were obtained at different levels of PL (3-11 cmH2O). We measured tracheal flow and tracheal and alveolar pressure (using alveolar capsules) in open-chest animals during mechanical ventilation (tidal volume 6 ml/kg, frequency 1 Hz) and calculated Raw by subtracting tissue from total lung resistance. For interspecies comparisons, data were standardized using percent change in Raw (delta % Raw) at PL of 3 cmH2O during baseline and, after MCh, log-scaled delta % Raw at PL of 3 cmH2O. We found that increasing lung volume decreased Raw both at baseline and after MCh in both species. However, changes were far smaller in guinea pigs. During baseline, the slope of the delta % Raw/delta PL was -3.37 and -12.48 %/cmH2O for guinea pigs and rats, respectively (P < 0.001). After MCh, the slope of delta log %Raw/delta PL was -0.065 and -0.154 cmH2O-1 for guinea pigs and rats, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1992

Lung tissue resistance during contractile stimulation: structural damping decomposition.

Research in the mechanics of soft tissue, and lung tissue in particular, has emphasized that dissipative processes depend predominantly on the viscous stress. A corollary is that dissipative losses may be expressed as a tissue viscous resistance, (Rti). An alternative approach is offered by the structural damping hypothesis, which holds that dissipative processes within soft tissue depend directly more on the elastic stress than on the viscous stress. This implies that dissipative and elastic processes within lung tissues are coupled at a fundamental level. We induced alterations of Rti by exposing canines to aerosols of the constrictors prostaglandin F2 alpha, histamine, and methacholine and by changing volume history. Using the structural damping paradigm, we could separate those alterations in Rti into the product of two distinct contributions: change in the coefficient of coupling of dissipation to elastance (eta) and change in the elastance itself (Edyn). Response of Edyn accounted for most of the response of resistance associated with contractile stimulation; it accounted for almost all the response associated with differences in volume history. The eta changed appreciably with constriction but accounted for little of the response of Rti with volume history. According to the structural damping hypothesis, induced changes in eta with constriction must reflect changes in the kinetics of the stress-bearing process, i.e., differences in cross-bridge kinetics within the target contractile cell and/or differences in the influence of the target cell on other stress-bearing systems. We conclude that, regardless of underlying processes, the structural damping analysis demonstrates a fundamental phenomenological simplification: when Edyn responds, Rti is obligated to respond to a similar degree.

Airway Resistance↗

PubMed1992

Lung tissue behavior during methacholine challenge in rabbits in vivo.

Previous studies have shown that lung challenge with smooth muscle agonists increases tissue viscance (Vti), which is the pressure drop between the alveolus and the pleura divided by the flow. Passive inflation also increases Vti. The purpose of the present study was to measure the changes in Vti during positive end-expiratory pressure- (PEEP) induced changes in lung volume and with a concentration-response curve to methacholine (MCh) in rabbits and to compare the effects of induced constriction vs. passive lung inflation on tissue mechanics. Measurements were made in 10 anesthetized open-chest mechanically ventilated New Zealand male rabbits exposed first to increasing levels of PEEP (3-12 cmH2O) and then to increasing concentrations of MCh aerosol (0.5-128 mg/ml). Lung elastance (EL), lung resistance (RL), and Vti were determined by adjusting the equation of motion to tracheal and alveolar pressures during tidal ventilation. Our results show that under baseline conditions, Vti accounted for a major proportion of RL; during both passive lung inflation and MCh challenge this proportion increased progressively. For the same level of change in EL, however, the increase in Vti was larger during MCh challenge than during passive inflation; i.e., the relationship between energy storage and energy dissipation or hysteresivity was dramatically altered. These results are consistent with a MCh-induced change in the intrinsic rheological properties of lung tissues unrelated to lung volume change per se. Lung tissue constriction is one possible explanation.

Administration, Inhalation↗

PubMed1992

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)

Aerosols↗

PubMed1992

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.

Airway Resistance↗

PubMed1991

Contribution of quasi-static tissue hysteresis to the dynamic alveolar pressure-volume loop.

We obtained dynamic and flow-interrupted (quasi-static) pressure-volume loops from the lungs of anesthetized paralyzed open-chest mongrel dogs by measuring tracheal flow and pressure and alveolar pressure (PA) in three different regions using alveolar capsules. We used continuous tidal ventilation to obtain dynamic PA-volume loops and used the single-breath-interrupter technique to construct quasi-static pressure-volume loops for the same tidal volume (VT). We used three different VT's (15 and 20 ml/kg and inspiratory capacity) under control conditions and a VT of 15 ml/kg after methacholine-induced bronchoconstriction. We found that quasi-static hysteresis was negligible under control conditions for VT of 15 and 20 ml/kg. Quasi-static hysteresis became more important (36 +/- 11% of the corresponding dynamic PA-volume loop) during inspiratory capacity ventilation and after induced bronchoconstriction (27 +/- 12% of the corresponding dynamic PA-volume loop). We conclude that during tidal breathing near functional residual capacity "true" static hysteresis is negligible and that purely viscoelastic processes can explain lung mechanical behavior. For higher volume ventilation and after methacholine-induced constriction, quasi-static hysteresis accounted for a more important portion of dynamic tissue hysteresis. This suggests either that a more complex model, e.g., one including plastic processes, should be invoked or that the lung exhibits longer viscoelastic time constants as peak distending stresses become greater.

Animals↗

PubMed1991

Maximal methacholine-induced constriction in rabbit lung: interactions between airways and tissue?

Six anesthetized paralyzed open-chest New Zealand White male rabbits were studied to obtain the maximal or plateau response to the inhalation of methacholine. Tracheal flow, tracheal pressure, and, by use of alveolar capsules, alveolar pressure were measured during tidal mechanical ventilation. We calculated total lung resistance (RL), tissue viscance (Vti), and lung elastance by digital fitting of the equation of motion to changes in tracheal and alveolar pressure. Airways resistance (Raw) was calculated as RL-Vti. Measurements were made under control conditions and after delivery of increasing concentrations of methacholine aerosol (0.5-128 mg/ml). We found that Vti accounted for the major proportion of RL both under control conditions (64.5 +/- 15.9%) and after methacholine-induced constriction (83.6 +/- 11.8%). There was a significant negative correlation between logarithmic percent change in Raw and Vti at the onset of the plateau response (r = 0.973). Furthermore, the slope of the relationship between log change in Vti and log change in Raw during the plateau response was strongly correlated with the degree of tissue response at the onset of the plateau (r = 0.957). Vti was positively correlated with lung elastance both before and during the plateau response (r = 0.946). We propose that the negative correlation between tissue resistance and Raw at the level of the plateau is consistent with a model of a mechanically interdependent lung, where decreases in airway caliber are limited by the constriction of the surrounding parenchyma.

Airway Resistance↗

PubMed1991

Histamine-induced constriction of canine peripheral lung: an airway or tissue response?

We compared the histamine responsiveness of peripheral airways (less than 6.0 mm diam) and parenchymal tissues in eight anesthetized paralyzed open-chest mongrel dogs. We measured pressure in a peripheral bronchus by using an antegrade wedged catheter and pressure in the alveolar region subtended by the wedged bronchus by using an alveolar capsule. Sinusoidal volume oscillations at a frequency of 0.5 Hz were delivered by a linear motor pump into the segment through the wedged catheter. We calculated the resistance of the segment (Rseg) and partitioned Rseg into tissue viscance (i.e., proportional to the resistive pressure drop between the alveolus and the pleura) and peripheral airway resistance. Measurements were taken under baseline conditions and after delivery of increasing concentrations of aerosolized histamine (0.1 micrograms/ml to 100.0 mg/ml) into the segment. We found that the histamine responsiveness of the peripheral airways and lung tissues varied markedly within a given dog. In four of eight dogs the airways were more responsive to histamine, in three of eight the tissues were more responsive, and in one of eight the response was equivalent at the two sites. We conclude that in a given animal, there is marked heterogeneity in the histamine responsiveness of the peripheral airways and parenchymal tissues and that either may dominate responsiveness in the peripheral lung.

Animals↗

PubMed1990

Interpretation of interrupter resistance after histamine-induced constriction in the dog.

The interrupter method for measuring respiratory system resistance involves interrupting flow at the airway opening and measuring the resultant changes in pressure. We have recently shown (J. Appl. Physiol. 65: 408-414, 1988) that in open-chest mongrel dogs, under control conditions, the initial rapid pressure change (delta Pinit) reflects conducting airway resistance and the subsequent gradual pressure change (delta Pdif) reflects stress recovery of the tissues. We questioned whether the same interpretation would apply after induced constriction. Accordingly, we performed interruption experiments on anesthetized, paralyzed, tracheostomized, open-chest mongrel dogs during passive expiration, measuring pressure at the trachea and in three different alveolar regions with alveolar capsules. We recorded measurements before and after the administration of increasing concentrations of histamine aerosol (0.1-30.0 mg/ml). We found a significant increase in the heterogeneity of alveolar pressures during the relaxed expiration with increasing concentrations of histamine. Despite the introduction of significant mechanical heterogeneities, delta Pinit still reflected the pressure drop as the result of the resistance of the conducting airways. delta Pdif, however, reflected a combination of the stress recovery of the tissues and pendelluft.

Airway Resistance↗

PubMed1989

Regional variability in the response of collateral resistance to histamine in the dog: effects of cyclooxygenase inhibition.

The aim of the study was to examine the role of cyclooxygenase metabolites in determining the variability in histamine responsiveness of the collateral channels of different lung segments of the dog. Using the wedged bronchoscope technique we measured the change in collateral resistance (Rcoll) to aerosolized histamine in two different lung segments of 5 anaesthetized, paralyzed, intubated, mongrel dogs. The same lung segments were examined twice under baseline conditions, and twice after indomethacin (INDO) pretreatment. Rcoll measurements were obtained under control conditions, after saline aerosol, and then after increasing concentrations of histamine (range 0.1 microgram/ml-10.0 mg/ml) were ultrasonically nebulized into the wedged segment. The concentration of histamine that elicited a 50% increase in Rcoll was calculated by log linear interpolation. In addition we performed bronchoalveolar lavage (BAL) in the wedged segment at the completion of the concentration-response curves, and assayed the BAL fluid for TXB2, PGE2, and 6-oxo-PGF1 alpha. The geometric mean ratio of histamine responsiveness between lung segments of each animal was 42.5-fold under control conditions and fell to 9.1-fold after INDO (P less than 0.05). While the concentration of TXB2 fell in the BAL after INDO, concentrations of PGE2 and 6-oxo-PGF1 alpha did not. Moreover, there was no correlation between levels of prostanoids and either responsiveness or variability in responsiveness of the collateral channels. Hence while cyclooxygenase blockade altered the regional variability in histamine responsiveness in the collateral channels, this change was not reflected in the levels of prostanoids in the BAL fluid.

Animals↗

PubMed1989

Dynamics of the collateral pathways of canine lungs after flow interruption.

After interruption of a constant flow (Vcoll) delivered through a bronchoscope into a wedged segment of lung, the pressure at the tip of the bronchoscope (Pb) often decays in a pattern seemingly indicative of two time constants. We tested the hypothesis that the initial more rapid component of the decay is associated with pressure equilibration across the bronchial resistance (Rb), separating bronchoscope tip from alveolus, and that the slower component is associated with pressure equilibration across the collateral pathways separating the wedged segment from surrounding regions. In eight open-chest mongrel dogs, we affixed an alveolar capsule to the segment subtended by the wedged bronchoscope and measured alveolar pressure (PA) and Pb during delivery of Vcoll into the segment and after its sudden interruption. Under both control conditions and after delivery of aerosolized histamine (1.0 or 10 mg/ml), we were unable to demonstrate a gradient between Pb and PA either during constant flow or after flow interruption. Whenever the decay of Pb was not monoexponential, neither was that of PA. Thus there was no evidence of an appreciable Rb, and the rapid component of the decay must be attributable to other factors. In a second protocol, we examined whether behavior departing from monoexponential decay was attributable to the presence of multicompartment behavior within the wedged segment or rather reflected the behavior of a single homogeneous but nonlinear compartment. In five closed-chest dogs, we systematically varied the initial Pb by changing Vcoll and recorded nonexponential pressure decay after flow interruption.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1989

A comparison of the dose-response behavior of canine airways and parenchyma.

We compared the histamine responsiveness of canine airways and parenchymal tissues in six anesthetized paralyzed open-chest mongrel dogs, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue viscance (Vti). Pressure was measured during tidal breathing (frequency was 0.3 Hz) at the trachea and in three alveolar regions by use of alveolar capsules. Measurements were taken before and after the delivery of increasing concentrations of aerosolized histamine (0.1-30 mg/ml). We found that Vti accounted for 78 +/- 8% of RL under base-line conditions; this proportion remained relatively constant throughout the histamine concentration-response curve. There was a significant correlation between percent change in Vti and percent change in Raw at all levels of histamine-induced constriction (P less than 0.001). Moreover, the sensitivity of the tissues and airways (defined as the concentration of histamine required to double resistance) was remarkably similar. We conclude that, at this frequency of ventilation, Vti accounts for the major portion of RL both under base-line conditions and after histamine-induced constriction. Although increases in RL cannot be attributed solely to events occurring in the airways, the close correlation between changes in Raw and Vti and the similar sensitivities of the two support the use of indexes reflecting changes in airway caliber as an indicator of overall lung histamine responsiveness.

Aerosols↗

PubMed1988

Temporal and regional variability of collateral resistance response to histamine.

Using the wedged bronchoscope technique, we measured the changes in collateral resistance (Rcoll) in dogs resulting from exposure to aerosols of increasing concentrations of histamine. Histamine dose-response curves were performed in each of two to three separate lobar segments of an individual mongrel dog's lungs. Five dogs were studied. The same segments were reexamined on later occasions (2-11 wk apart) to determine whether the responsiveness to histamine had altered with time. Measurements of base-line Rcoll for a given segment were reproducible (coefficient of variation 0.48). In contrast, we observed that the estimated dose of histamine required to increase Rcoll by 50% (ED150Rcoll) was extremely variable both among lung segments of an individual dog on a single experimental day (geometric mean variability of 40-fold) and for a given segment when reexamined on repeated occasions (geometric mean variability of 47-fold). The ED150Rcoll did not correlate with the base-line Rcoll. The degree of variability we observed suggests that peripheral contractile elements are under the influence of powerful local modulating factors that vary both regionally and temporally.

Airway Resistance↗

PubMed1988

Interrupter resistance elucidated by alveolar pressure measurement in open-chest normal dogs.

The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the mouth while measuring the pressure just distal to the point of interruption. The pressure signal observed invariably exhibits two distinct phases. The first phase is a very rapid jump, designated delta Pinit, which occurs immediately on interruption of flow. The second phase is designated delta Pdif and is a further pressure change in the same direction as delta Pinit but evolving over several seconds. The physiological interpretations of delta Pinit and delta Pdif have been somewhat unclear. Delta Pinit has been taken to equal the pressure drop across the pulmonary airways, possibly with a contribution from the tissues of the respiratory system. Delta Pdif can arise, in principle, from two sources: gas redistribution throughout the lung after interruption of flow and stress recovery within the tissues. To resolve these issues we performed interruption experiments on anesthetized paralyzed, tracheotomized, open-chest normal dogs during passive expiration while measuring alveolar pressures at three sites with alveolar capsules. We found that, in the absence of the chest wall, delta Pinit reflects only the resistance of the airways and that delta Pdif can be ascribed almost entirely to the stress recovery properties of lung tissues.

Airway Resistance↗

PubMed1988

Lung inflation does not increase maximal expiratory flow during induced obstruction in the dog.

A deep inflation (DI) reverses induced bronchoconstriction in normal human subjects whether assessed by airway resistance before and after a DI or by isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume (PEFV) vs. maximum expiratory flow-volume (MEFV) maneuvers. These observations suggest that with induced constriction the hysteresis of airways exceeds that of the parenchyma. In contrast with humans, a previous study of ours on dogs indicated that induced increases in airway resistance were unaffected by DI, suggesting that hysteresis of airways and parenchyma were equal. We hypothesized therefore that in constricted dog lungs, any differences that might arise in isovolumic Vmax between PEFV and MEFV maneuvers would not be due to changes in airway caliber but rather would be wholly determined by isovolumic differences in deflational recoil pressures. Recoil pressures were dynamically measured using six separate alveolar capsules in each of six dogs. At base line there were no significant differences between isovolumic recoil pressures or maximal flows with volume history, suggesting equal degrees of airway and parenchymal hysteresis. After histamine-induced constriction there were also no isovolumic differences in flows, but due to striking nonhomogeneities in dynamic recoil pressure among alveolar capsules, it was not possible to express a single meaningful recoil pressure pertinent to the lungs as a whole. These findings are consistent with the idea that isovolumic comparisons of Vmax serve as a reasonable indicator of changes in the relative degree of airway and parenchymal hysteresis.

Airway Obstruction↗

PubMed1988

Differential responses of tissue viscance and collateral resistance to histamine and leukotriene C4.

Alterations in tissue viscance (Vti) and collateral resistance (Rcoll) are both used as indexes of peripheral lung responses. However, it is not known whether the two responses reflect the effects of activation of the same contractile elements. We measured differential responses in Vti and Rcoll to histamine and leukotriene (LT) C4 to determine whether each evoked a similar pattern of response. Using the wedged bronchoscope constant-flow technique, we measured Rcoll in lobar segments of anesthetized, paralyzed, open-chest, mechanically ventilated mongrel dogs. In addition, we measured (with an alveolar capsule) alveolar pressure (PA) within the segment under study. This allowed us to calculate Vti, the component of the PA change in phase with segment flow. Rcoll and Vti measurements were obtained under base-line conditions and after local delivery of aerosols generated from histamine and LTC4. In five out of five lobes studied with both histamine and LTC4, the fractional Rcoll response to histamine was greater than the fractional Rcoll response to LTC4. In contrast, in four out of five lobes examined, the fractional increase in Vti accompanying the histamine response was less than the fractional increase in Vti accompanying LTC4 administration. These data suggest that anatomically distinct contractile elements influence Vti and Rcoll insofar as LTC4 and histamine evoke quantitatively different changes in these two indexes of peripheral lung responses.

Airway Resistance↗

PubMed1987

Partitioning of pulmonary resistance during constriction in the dog: effects of volume history.

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.

Airway Resistance↗