Biomedical subjects

M S Ludwig

Publications and source records attributed to M S Ludwig.

At least 37 records · Page 2Linked to original sources

PubMed1998

Antigen-induced responses in lung parenchymal strips during sinusoidal oscillation.

We have recently demonstrated that tissue resistance increases during the early response to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate in vitro the dynamic tissue response to antigen challenge and the involvement of the mediators, i.e., serotonin (5HT) and leukotriene D4 (LTD4). In addition, we questioned whether strips from sensitized rats responded differently to nonspecific challenge compared with those of unsensitized controls. We sensitized Brown-Norway rats with ovalbumin and performed experiments using strips of subpleural parenchyma. Tissue strips were challenged with ovalbumin in the bath; in some experiments the tissues were exposed to methysergide (10(-6) M), a 5HT antagonist, or MK-571 (10(-6) M), a LTD4 receptor antagonist, or both, prior to challenge. At the end of the experiment all tissues were exposed to carbacholine (10(-3) M). Oscillation mechanics of tissue strips were studied and values of resistance (R), elastance (E), and hysteresivity (eta) were obtained. During ovalbumin challenge in sensitized tissues, R, E, and eta increased significantly (% change in R, 12.1 +/- 2.1%; % change in E, 3.8 +/- 1.3%; % change in eta, 9.3 +/- 2.8%). Both methysergide and MK-571 reduced the increase in R (3.0 +/- 0.6 and 3.2 +/- 0.8%, respectively, p < 0.05 vs. ovalbumin). There was no difference between sensitized and unsensitized strips in the response to carbacholine challenge. These data suggest that the oscillatory behaviour of tissue strips from sensitized rats is altered after ovalbumin challenge. The mechanism of that response is mediated by both 5HT and LTD4.

Animals↗

PubMed1996

Effect of the route and mode of agonist delivery on functional behaviour of the airways.

There is evidence that the mode of smooth muscle agonist delivery affects the changes induced in lung mechanical properties. The object of this investigation was to study modifications in airway behaviour associated with different modes of agonist delivery. Tracheal (Ptr) and alveolar pressure (PA) and flow (V) were measured in open-chested, mechanically ventilated (f = 1 Hz, VT = 10 ml/kg, PEEP = 4 cm H2O) rats under baseline conditions and during administration of repeated intravenous (i.v.) bolus, i.v. continuous infusion and aerosols of methacholine (MCh). We calculated lung elastance (EL) and lung resistance (RL) by fitting the equation of motion to changes in Ptr and V. We assessed the patency of the airway pathways and local dynamic hyperinflation by comparing Ptr vs PA. Comparison of the three different modes of MCh delivery showed a difference in the functional behaviour of the airways. In the aerosol group a larger incidence of highly constricted airways was observed. Conversely, the i.v. groups showed a larger incidence of regional dynamic hyperinflation. In the bolus group a different time course in the development of dynamic hyperinflation was observed for different pathways within the same animal. For consecutive challenges a given pathway tended to behave in the same manner, suggesting the response was characteristic for that pathway. In this study we have shown that, even though different airway pathways show different intrinsic reactivity, the mode of agonist delivery plays a role in determining functional airway behaviour.

Animals↗

PubMed1996

Characterization of the anatomical structures involved in the contractile response of the rat lung periphery.

1. When lung parenchymal strips are challenged with different smooth muscle agonists, the tensile and viscoelastic properties change. It is not clear, however, which of the different anatomical elements present in the parenchymal strip, i.e., small vessel, small airway or alveolar wall, contribute to the response. 2. Parenchymal lung strips from Sprague Dawley rats were suspended in an organ bath filled with Krebs solution (37 degrees C, pH = 7.4) bubbled with 95%O2/5%CO2. Resting tension (T) was set at 1.1 g and sinusoidal oscillations of 2.5% resting length (L0) at a frequency of 1 Hz were applied. Following 1 h of stress adaptation, measurements of length (L) and T were recorded under baseline conditions and after challenge with a variety of pharmacological agents, i.e., acetylcholine (ACh), noradrenaline (NA) and angiotensin II (AII). Elastance (E) and resistance (R) were calculated by fitting changes in T, L and delta L/ delta t to the equation of motion. Hysteresivity (eta, the ratio of the energy dissipated to that conserved) was obtained from the equation eta = (R/E)2 pi f. 3. In order to determine whether small airways or small vessels accounted for the responses to the different pharmacologic agents, further studies were carried out in lung explants. Excised lungs from Sprague Dawley rats were inflated with agarose. Transverse slices of lung (0.5-1.0 mm thick) were cultured overnight. By use of an inverted microscope and video camera, airway and vascular lumen area were measured with an image analysis system. 4. NA, ACh and AII constricted the parenchymal strips. Airways constricted after all agonists, vessels constricted only after All. Atropine (Atr) pre-incubation decreased the explanted airway and vessel response to AII, but no difference was found in the parenchymal strip response. 5. Preincubation with the arginine analogue N omega-nitro-L-arginine (L-NOARG) did not modify the response to ACh but mildly increased the oscillatory response to NA after co-preincubation with propranolol (Prop). 6. These results suggest that during ACh and NA challenge, small vessels do not contribute substantially to the parenchymal strip response. The discrepancy between results in airways, vessels and strips when Atr was administered prior to AII implicates a direct contractile response in the parenchymal strip.

Acetylcholine↗

PubMed1996

Airway and tissue behavior during early response in sensitized rats: role of 5-HT and LTD4.

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the role of the potential ER mediators 5-hydroxytryptamine (5-HT) and leukotriene D4 (LTD4) in the airway and tissue response. We sensitized the rats with ovalbumin (OA) and performed experiments on anesthetized, open-chested, mechanically ventilated [breathing frequency = 1 Hz, tidal volume = 12 ml/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O] animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw). To assess the effects of LTD4 and 5-HT, we administered the antagonists methysergide (5-HT antagonist) and MK-571 (LTD4 antagonist) before challenge. To assess lung morphometry during the ER, the lungs of four animals from each group were frozen with liquid nitrogen (PEEP = 3 cmH2O). Airway constriction was assessed by measuring the ratio of the airway lumen to the ideally relaxed airway (Abm/A*bm). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue to air space, and SD of the two (SD-Lm and SD-ATI). In all animals receiving OA but no antagonists, an ER was seen (RL, Rti, and Raw = 180.7 +/- 6.1, 155.4 +/- 8.2, and 223.1 +/- 14.0% of baseline, respectively). Methysergide significantly inhibited the ER (RL, Rti, and Raw = 117.0 +/- 5.9, 101.2 +/- 1.6, 133.7 +/- 10.2%, respectively), whereas MK-571 partially reduced the ER (RL, Rti, and Raw = 144.2 +/- 5.6, 132.9 +/- 5.7, and 155.5 +/- 9.2%, respectively). Abm/A*bm was significantly decreased, and SD-Lm and SD-ATI were significantly increased in animals receiving OA alone and in those receiving MK-571 before OA challenge. These data suggest that alterations in both airways and tissues contribute to the ER and that 5-HT and, to a lesser degree, LTD4 are important mediators of the ER in this rat model of extrinsic asthma.

Air Pressure↗

PubMed1996

Effects of lung volume on airway resistance during induced constriction in papain-treated rabbits.

It has been reported that both the elasticity of the cartilage and airway-parenchymal interdependence can modify shortening of the airway smooth muscle and airway narrowing during induced constriction. We hypothesized that induced softening of the cartilage could alter airway compliance and/or the forces of mechanical interdependence, resulting in an increased degree of airway narrowing in response to a contractile stimulus. To test this hypothesis, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in papain-treated (n = 6) and control rabbits (n = 6). With use of the alveolar capsule technique, Raw was directly measured under baseline conditions at different levels of end-expiratory transpulmonary pressure (Ptp = 4-12 cmH2O). Then aerosolized MCh was delivered (0.2-25 mg/ml) and measurements were performed at different levels of Ptp (4 and 12 cmH2O). From measured tracheal flow and tracheal and alveolar pressure in open-chest animals during mechanical ventilation (tidal volume = 6 ml/kg, breathing frequency = 1 Hz), we calculated Raw by subtracting tissue resistance from lung resistance. Papain treatment significantly increased Raw both under baseline conditions and after induced constriction. We found that increasing Ptp decreased Raw before and after MCh in both groups; however, the effects of changing Ptp on Raw were less in papain-treated animals. These observations suggest that both cartilage elasticity and mechanical interdependence are important determinants of airway smooth muscle shortening. The observation that volume dependence of Raw was less in papain-treated animals is consistent with the hypothesis that papain effects significant changes in the parenchymal attachments.

Airway Resistance↗

PubMed1995

How mode of stimulus affects the relative contribution of elastance and hysteresivity to changes in lung tissue resistance.

Challenges with high concentrations of constrictor agonist delivered by intravenous vs. aerosol result in different modifications of the mechanical properties of lung tissues. We questioned whether low doses of a smooth muscle agonist administered via different routes (aerosol, i.v. bolus, i.v. continuous infusion) or an increase in positive end-expiratory pressure (PEEP) would result in different mechanical perturbations of lung tissues. Tracheal and alveolar pressures and flow were measured in open-chest mechanically ventilated (frequency 1 Hz, tidal volume 10 ml/kg, PEEP 4 cmH2O) rats under baseline conditions and after administration of low doses of methacholine or after increases in PEEP. We calculated lung elastance (EL), lung resistance, and tissue resistance (Rti) by fitting the equation of motion to changes in tracheal and alveolar pressures. Airway resistance and hysteresivity (eta) were derived from the above measurements. For comparable increases in Rti, the aerosol and PEEP groups showed large increases in EL with a decrease in eta, whereas the two intravenous groups showed large increases in eta with smaller increases in EL. The largest contribution of eta to the overall increase in Rti was seen in the intravenous bolus group. When induced changes in EL vs. induced changes in eta were plotted, different relationships were found for the four groups. We conclude that despite similar increases in Rti a different kind of mechanical perturbation occurred in the lung tissues that depended on the nature of the stimulus.

Aerosols↗

PubMed1995

Does the anatomic makeup of parenchymal lung strips affect oscillatory mechanics during induced constriction?

Parenchymal tissue strips have been used to investigate the mechanical behavior of the lung parenchyma. We questioned whether the relative amounts of alveolar, blood vessel, and bronchial walls would be important when the contractile response of parenchymal strips from Sprague-Dawley rats was studied. One group of strips was cut from the subpleural edge and another from between 1 and 3 mm proximal to the pleura. Strips were suspended in an organ bath filled with Krebs solution (37 degrees C, pH 7.4) bubbled with 95% O2-5% CO2. Resting tension (T) was set at 1.1 g, and sinusoidal oscillations of 2.5% resting length at a frequency of 1 Hz were applied. Measurements of length and T were recorded during baseline conditions and after acetylcholine (10(-3) M) was added to the bath. Elastance, resistance, and hysteresivity (the ratio of the energy dissipated to that conserved) were calculated. Strips were fixed in Formalin at a T of 1 g, histological sections were prepared, and the fractional areas of alveolar, blood vessel, and bronchial walls were measured by using point counting. Significant differences were found between the two groups of strips in the acetylcholine response and anatomic makeup. The magnitude of the changes of all the mechanical parameters were correlated with the volume proportions of the different anatomic constituents when all the strips were plotted together but not when the subpleural strips were considered alone. We conclude that subpleural parenchymal strips are a sound model of parenchymal lung behavior. When more proximal strips are studied, the amount of bronchial wall may play an important role in determining the hysteretic response.

Acetylcholine↗

PubMed1995

Lung tissue distortion in response to methacholine in rats: effect of lung volume.

We have previously shown that, after induced constriction, there is substantial distortion of the parenchymal tissues. In this study we investigated whether differences in parenchymal morphology occurred when the lung was constricted at different lung volumes. We measured tracheal pressure and calculated lung resistance in mechanically ventilated rats under control conditions and after aerosol administration of methacholine (256 mg/ml) at different positive end-expiratory pressures (PEEP = 7, 5, and 3 cmH2O). The lungs were frozen with liquid nitrogen at different PEEP levels and processed via freeze substitution. We measured airway constriction as the ratio of the airway lumen to the ideally relaxed area, alveolar size by measuring the mean linear intercept between alveolar walls, and tissue distortion as the standard deviation of the number of intercepts in the 40 fields sampled per lung. The increase in lung resistance was largest at PEEP = 3 cmH2O. Whereas airway constriction decreased and alveolar size increased at higher lung volume (PEEP = 7 cmH2O), tissue distortion did not change. These data suggest that parenchymal distortion after induced constriction was not attributable to airway narrowing and/or closure.

Aerosols↗

PubMed1995

Dynamic elastance and tissue resistance of isolated liquid-filled rat lungs.

The effect of the surface forces of the alveolar air-liquid interface on the dynamic behavior of lung tissue was investigated in five isolated liquid-filled rat lungs. The lungs were subjected to 0.04-Hz sinusoidal oscillation (1.5-ml tidal volume) at lung volume (VL) levels ranging from volume at zero pressure (V0) + 4 ml to V0 + 10 ml. Oscillations were performed at each VL after inflation of the lungs from V0. Alveolar pressure (PA) was measured with an alveolar capsule attached to the visceral pleura. Dynamic elastance (Edyn), tissue resistance (Rti), and hysteresivity [eta = Rti omega/Edyn, where omega is angular frequency (2 pi x frequency)] were computed from PA and VL changes. Edyn was 59.6 +/- 4.3 Pa/ml at V0 + 4 ml and varied little up to V0 + 7 ml. Thereafter, Edyn increased markedly with VL, reaching 102 +/- 16 Pa/ml at V0 + 10 ml. No significant difference was found between elastance computed from PA and that computed from pressure recorded at the airway opening. Rti was 35.2 +/- 3.6 Pa.s.ml-1 and exhibited a VL dependence similar to that of Edyn. As a result, eta was 0.16 and did not vary significantly in the explored VL range. We conclude that PA can be reliably measured in the liquid-filled lung by means of alveolar capsules. In the liquid-filled lung, Edyn was smaller than and eta was similar to values reported for air-filled lungs. Hence, surface tension accounts for a considerable part of elastance and Rti of the air-filled lung within the volume range of normal breathing.

Animals↗

PubMed1995

In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4.

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the in vitro airway and tissue responses to antigen and the involvement of the potential mediators serotonin (5-HT) and leukotriene D4 (LTD4). We sensitized Brown-Norway rats with ovalbumin (OA) and subsequently challenged bronchial rings and subpleural parenchymal strips with OA in the organ bath. In selected experiments tissues were incubated with methysergide (a 5-HT receptor antagonist), ketanserin (a 5-HT2 receptor antagonist), MK-571 (a LTD4 receptor antagonist), or MK-886 (5-lipoxygenase inhibitor) prior to challenge. Both bronchial rings and parenchymal strips constricted in response to OA. Methysergide and ketanserin completely inhibited OA-induced constriction of bronchial rings. The effect of MK-571 was not significant, whereas MK-886 partially blocked OA-induced bronchial constriction, suggesting a potential role for LTC4 in antigen-induced airway constriction. In parenchymal strips, methysergide, ketanserin, MK-571, and MK-886 all partially inhibited the OA response, whereas the combinations of methysergide and MK-571 or ketanserin and MK-886 completely ablated the response. These data suggest that both bronchial rings and parenchymal strips constrict after OA challenge but that the relative contributions of 5-HT and LTD4 to the allergic response in central airways and parenchymal tissues differ.

Airway Resistance↗

PubMed1994

Heterogeneous regional behavior during forced expiration before and after histamine inhalation in dogs.

We studied the evolution of alveolar pressure (PA) heterogeneity during the course of forced expiration in the lungs of six anesthetized open-chest dogs. Using an alveolar capsule technique, we measured PA simultaneously in six lung regions during full maximal forced deflations before and after administering aerosolized histamine. Flow was measured plethysmographically with volume obtained by flow integration. Heterogeneity was expressed as the coefficient of variation (CV) of regional PA after 25% of the vital capacity had been expired from total lung capacity. The CV in in vivo open-chest canine lungs (21.3%) was significantly greater than that we measured previously in excised lungs (8.7%) (P < 0.02). Inhalation of aerosolized solutions of histamine produced significant increases in interregional heterogeneity (CV = 35.5 and 38.8% after 3 and 10 mg/ml of histamine, respectively; P < 0.025). After histamine, the vital capacity was reduced and the configuration of the flow-volume curve demonstrated some shortening of the flow plateau commonly observed in dogs. Changes in the flow-volume relationship failed, however, to reflect well the marked degree of heterogeneity of PA after histamine administration. These findings may be reconciled on the basis of interdependence of regional expiratory flows. Reductions in flow from obstructed regions appear to be compensated by increases in flow from unobstructed regions and thus mask upstream nonuniformities. These mechanisms may explain in part why the maximal expiratory flow-volume curve has been a relatively insensitive tool for the detection of early nonuniform airway disease.

Administration, Inhalation↗

PubMed1994

Airway and tissue behavior during induced constriction in rats: intravenous vs. aerosol administration.

The distribution of contractile agonist during intravenous (i.v.) or aerosol (AR) administration is likely to be different. We questioned whether the different pattern of distribution would result in different effects on lung tissue response. We measured tracheal and alveolar pressure in open-chest mechanically ventilated [frequency 1 Hz, tidal volume 8 ml/kg, positive end-expiratory pressure (PEEP) 3 cmH2O] rats under control conditions and after i.v. or AR administration of saline or methacholine (MCh; i.v., 50 micrograms.kg-1.min-1; AR, 256 mg/ml). We calculated lung elastance and resistances of lung, tissue, and airway by fitting the equation of motion to changes in tracheal and alveolar pressure. Lungs were then frozen in situ with liquid nitrogen (PEEP=3 cmH2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of airway lumen to ideally relaxed area. Tissue distortion was assessed by measuring mean linear intercept between alveolar walls (Lm), atelectasis index (ATI) derived by calculating ratio of tissue to air space, and SD of Lm and ATI. I.v. and AR MCh increased lung resistance to a similar degree. However, changes in tissue resistance and lung elastance after AR MCh were significantly greater than those after i.v. MCh, whereas the change in airway resistance was significantly less. After i.v. MCh, airway constriction was prominent and evenly distributed. After AR MCh, airway constriction was less prominent and decreased as airway size decreased. Tissue distortion, i.e., SD of Lm and ATI, was significantly greater after AR than i.v. MCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

PubMed1994

Proposed nomenclature for quantifying subdivisions of the bronchial wall.

There is increasing interest in the structural components of the airway wall because of the airway remodeling that is observed in conditions such as asthma and chronic obstructive pulmonary disease and because of their contribution to changes in airway mechanics. This interest has stimulated several groups to make morphometric measurements on airway cross sections, and their results have been reported using a variety of nomenclature. We propose the adoption of a standard system of nomenclature that is based on accepted terms for subdivisions of the airway wall and has been agreed to by several groups working in this field.

Bronchi↗

PubMed1994

Structural composition of lung parenchymal strip and mechanical behavior during sinusoidal oscillation.

The lung parenchymal strip is comprised of many different anatomic elements, including small vessels, small airways, and alveolar walls. We questioned whether the relative amounts of these different structures are important in determining the mechanical behavior of this preparation during dynamic oscillations. We studied 16 parenchymal strips (10 x 2 x 2 mm) from 12 Sprague-Dawley rats. The strips were suspended in an organ bath filled with Krebs solution, bubbled with 95% O2-5% CO2, and maintained at 37 degrees C. One end of the strip was attached to a force transducer, and the other end was attached to a lever system that effected length (L) changes. We oscillated the strips at various resting tensions (T) (0.9 and 1.5 g), frequencies (0.1, 0.3, 0.6, and 1.0 Hz), and amplitudes (1.1, 2.4, and 5.3% of optimal L). We obtained T vs. L curves and calculated the resistance, elastance, and hysteresivity (ratio of energy dissipated to energy stored) of the tissue. At the end of the experiment, the strips were fixed in Formalin at T = 1 g. Histological sections were examined, and the amounts of airway, blood vessel, and alveolar wall were quantified using point counting techniques. We found that whereas resistance varied significantly with frequency and T, elastance and hysteresivity varied with only T. The fractional areas of alveolar, blood vessel, and bronchial wall were 86.3 +/- 0.5 (SE), 8.4 +/- 0.3, and 5.3 +/- 0.4%. Only hysteresivity and the fractional area of alveolar wall were significantly correlated at the lower resting tension (r = -0.76, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Airway and tissue responses during hyperpnea-induced constriction in guinea pigs.

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. On the basis of recent studies that show increases in tissue resistance after allergen exposure in sensitized rats, we hypothesized that lung tissues might also be involved in the pathophysiology in this asthma model. We measured tracheal pressure (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 4 cm H2O) guinea pigs under control conditions (regular breathing of warm, humidified air) and after dry gas hyperpnea challenge (HC, mixture of 95% O2 and 5% CO2, 150 breaths/min, 7 min). We calculated lung elastance (EL) and resistance of lung (RL), tissue (Rti), and airway (Raw) by fitting the equation of motion to changes in Ptr and PA. To assess the effects of volume history, we applied a single deep inflation (three times VT) in five HC animals. We performed morphometric analysis in five control and five HC animals, freezing the lungs with liquid nitrogen and processing the tissues via freeze substitution. HC significantly increased RL, Rti, Raw, and EL (424 +/- 62, 771 +/- 230, 287 +/- 33, 259 +/- 31% baseline, respectively). A deep inflation reduced RL, Rti, Raw, and EL by 30 +/- 4, 31 +/- 4, 29 +/- 6, 23 +/- 5%, respectively. In HC animals, the degree of airway constriction was most prominent in the larger airways; extensive tissue distortion was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Airway and tissue responses to antigen challenge in sensitized brown Norway rats.

It has recently been shown in several species that lung tissue resistance increases after administration of exogenous bronchoconstrictors. This finding suggests the possibility that lung parenchymal tissues could be involved in the pathophysiology of pulmonary allergic responses. To test this hypothesis, we sensitized Brown Norway rats with ovalbumin (OA) and performed experiments in anesthetized, open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 3 cm H2O) animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) under control conditions and after aerosol administration of saline (S) (n = 10) or OA (n = 14). To assess lung morphometry during the late response, the lungs of six S and six OA animals were frozen with liquid nitrogen (PEEP = 3 cm H2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed airway (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue/airspace, and the standard deviation (SD) of Lm and ATI. In the OA group, all animals demonstrated an early response (ER; RL, Rti, Raw = 183.5 +/- 7.7, 159.7 +/- 9.9, 232.5 +/- 17.2% baseline, respectively) and 11 animals showed a late response (LR; RL, Rti, Raw = 178.9 +/- 5.1, 191.3 +/- 11.5, 176.6 +/- 17.3% baseline, respectively). Neither ER nor LR were observed in the saline group.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1993

How changes in the serial distribution of bronchoconstriction affect lung mechanics.

It is generally accepted that methacholine (MCh) acts predominantly on the central airways and histamine (H) acts on the lung periphery. We hypothesized therefore that lung mechanics would be affected differently by H and MCh aerosols. In 12 anesthetized paralyzed open-chest mongrel dogs, we obtained MCh (0.1-30 mg/ml, n = 6) and H (0.1-30 mg/ml, n = 6) concentration-response curves. The alveolar capsule technique was used to partition lung resistance (RL) into airway (Raw) and tissue (Rti) components. The degree of mechanical heterogeneity across the lung was assessed by computing the coefficient of variation for five alveolar pressures during relaxed expirations. RL increased 823 +/- 202% after H and 992 +/- 219% after MCh. Rti increased 784 +/- 192% after H and 1,014 +/- 279% after MCh. Raw increased 1,098 +/- 297% after H and 1,275 +/- 332% after MCh. Elastance increased 342 +/- 53% after H and 423 +/- 88% after MCh. The coefficient of variation increased 279 +/- 65% after H and 252 +/- 55% after MCh. The patterns of change were similar throughout the H and MCh concentration-response curves. We conclude that H and MCh have comparable effects on lung mechanics and that the degree and pattern of heterogeneity inside the lung after constriction are the same regardless of the agent used. These data support the hypothesis that H and MCh have some similar direct effect on the lung parenchyma. Parenchymal deformation after MCh-induced central airway constriction alone would be unlikely to explain increases in Rti of this magnitude or changes in lung mechanics so similar to those induced by H.

Aerosols↗

PubMed1993

Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction.

Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063-16 mg/ml). In separate animals (n = 10), measurements were made at 3-13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction.

Aerosols↗