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Biomedical subjects

W Mitzner

Publications and source records attributed to W Mitzner.

At least 37 records · Page 2Linked to original sources
PubMed1993

Direct in vivo visualization of bronchodilation induced by inhalational anesthesia using high-resolution computed tomography.

BACKGROUND: Volatile anesthetics are effective at preventing and reversing bronchospasm, but their effects on baseline airway tone are controversial. While tantalum bronchography has been used in the past to measure one-dimensional airway diameter changes, this method has inherent problems associated with the irritant effects of tantalum. Until recently, no other direct noninvasive in vivo method to assess airway caliber was available. The present investigation assesses the effects of the inhalation anesthetic halothane on individual unstimulated airways in vivo. METHODS: Ten studies were performed in seven dogs. All dogs were initially anesthetized with 15 mg/kg thiopental followed by a 10-mg.kg-1 x h-1 maintenance dose. Following tracheal intubation the lungs were mechanically ventilated (15 ml/kg, 15 beats/min). The dogs subsequently received increasing doses of halothane (range 0.5-1.5%). On a separate day, the dogs were pretreated with atropine (0.2 mg/kg) and the study was repeated. Fifty sequential high-resolution computed tomography scans were obtained using a 1-s scan time, 137 kVp, 220 mA, 2-mm slice thickness, and 1-mm table feed. Airway areas ranging in size from 3 to 22 mm in diameter were measured and analyzed by one way analysis of variance and Bonferroni pair-wise comparisons of means. RESULTS: Halothane in concentrations of 0.5%, 1.0%, and 1.5% showed significant dose-dependent dilation of the airways (percent increase from control) that averaged 90 +/- 19% (mean +/- SEM), 128 +/- 20%, and 182 +/- 27%, respectively (P = .017). Atropine pretreatment alone significantly dilated the airways to 151 +/- 25% (P = .002) of their baseline value. Halothane caused no further airway dilation in atropine pretreated dogs. CONCLUSIONS: Halothane dilates baseline airways by blocking baseline vagal tone. Since baseline airway tone, airway wall thickness, and initial airway diameter are major determinants of airway reactivity, the observed dilation by halothane may be one of the mechanisms by which inhalational anesthetics decrease airway reactivity.

Anesthesia, Inhalation↗
PubMed1993

High-resolution computed tomography--physiologic correlation.

High-resolution computed tomography (HRCT) as a tool for investigation of bronchovascular and pulmonary responses to various physiologic and pharmacologic stimuli is a new field of application. The potential of this method has only recently been investigated in animal experiments. To date, research has focused on the determination of airway responses in the context of agonist challenge such as aerosolized or i.v. histamine, isotonic saline, halothane anesthesia, and hypoxia. Likewise, physiologic HRCT has been used in the elucidation of the pulmonary circulatory response to acute hypervolemia and hypoxia. Early results indicate that significant observations can be derived from HRCT as it is the only existing method that not only detects physiologic responses but, unlike existing methods, can characterize their site and locoregional differences. In this article, the rationale for and present status of physiologic HRCT is presented.

Bronchial Hyperreactivity↗
PubMed1993

Cationic proteins alter smooth muscle function by an epithelium-dependent mechanism.

Using a perfused guinea pig tracheal tube preparation, which allows the selective application of agonists to either the serosal or luminal surface, we have investigated whether two synthetic cationic proteins, poly-L-arginine and poly-L-lysine, can modify epithelium-dependent responses. With an intact epithelium, methacholine was approximately 150 times less potent when applied intraluminally than when applied extraluminally. This difference was abolished by chemically removing the epithelium with the detergent CHAPS. Intraluminal application of KCl induced a dose-related relaxation of a precontracted trachea, which was also abolished by epithelium removal. Perfusion of the luminal surface with cationic proteins for 1 h (10 micrograms/ml) increased the potency of intraluminally applied methacholine without modifying the responses to extraluminally applied methacholine. Cationic proteins also attenuated the relaxant effects of intraluminally applied KCl. These effects occurred in the absence of any overt epithelial cell damage. In contrast, when the serosal surface of the trachea was treated with poly-L-arginine, there was no modification of either methacholine-induced contraction or KCl-induced relaxation. The effects of poly-L-arginine were inhibited by coperfusion with the polyanions albumin (10 micrograms/ml) or heparin (100 micrograms/ml). In contrast to cationic proteins, intraluminal perfusion with a polyanion, poly-L-aspartate (10 micrograms/ml), failed to modify either methacholine-induced contraction or KCl-induced relaxation. Our data demonstrate that cationic proteins can modify epithelium-dependent responses in the airways. Although the precise mechanisms are unclear, a role is suggested for a charge-mediated interaction with the respiratory epithelium, resulting in airway smooth muscle dysfunction.

Albumins↗
PubMed1993

Individual airway constrictor response heterogeneity to histamine assessed by high-resolution computed tomography.

We directly measured the range of individual airway responses to aerosol and intravenous administration of histamine by using high-resolution computed tomography and then compared the heterogeneity in constriction responses between these two routes. Seven dogs were used for a total of eleven studies. Six of the seven dogs received intravenous histamine (100-300 micrograms/min) and five of the seven dogs received aerosolized histamine (0.01-3.0 mg/ml for 5 breaths). Data were analyzed using linear regression models calculating residual mean square values for each route of histamine as a measure of variability in the change in airway size. The residual mean square values for the absolute airway size after the aerosol and intravenous histamine challenges were 17.73 and 15.42, respectively, which were not significantly different [F(331,166) = 1.15, P = 0.32]. Also, there were no significant differences when we compared the log or the percent change in airway area for the two routes of administration. We conclude that the route of histamine administration does not significantly affect the heterogeneity of airway response, suggesting that the heterogeneity observed after the histamine challenge is predominantly controlled by local mechanisms in the airways.

Aerosols↗
PubMed1993

Effects of high-frequency ventilation and PEEP on carotid baroreceptor reflexes.

We tested the hypothesis that altering the pattern and/or magnitude of discharge of pulmonary stretch receptors (PSRs) would alter baroreceptor reflexes in anesthetized aortic-denervated cats. Carotid baroreceptor control of mean arterial pressure (MAP), heart rate (HR), and hindlimb perfusion pressure (PPhl) was examined by changing carotid sinus pressure (CSP) from 50 to 225 mmHg. The pattern of PSR discharge was changed by switching conventional mechanical ventilation (CMV) to high-frequency ventilation (HFV). Magnitude of PSR discharge was altered by changing positive end-expiratory pressure (PEEP). Altering the discharge pattern of PSR had no effect on CSP-MAP or CSP-PPhl relationships; small changes in HR were observed. Increasing PSR activity by increasing PEEP during CMV (from 3 to 9 cmH2O) depressed CSP-MAP relationship, set point, and threshold pressure. However, the depression in CSP-MAP relationship and set point during PEEP was unrelated to PSR activation, because these changes were not abolished after bilateral vagotomy. CSP-PPhl relationship was significantly elevated during PEEP before and after vagotomy, suggesting activation of a nonvagally mediated vasoconstrictory mechanism instead of PSR-mediated depressor reflex. CSP-HR relationship during PEEP showed a slight elevation, which was abolished after vagotomy. We conclude that despite minor increases in HR, altering the pattern of magnitude of PSR activity with HFV and PEEP has no significant effect on carotid baroreceptor regulation of systemic circulation. Hemodynamic changes observed during PEEP were likely due to its mechanical effect on cardiac output and activation of other cardiopulmonary receptors rather than to the increase in PSR activity.

Animals↗
PubMed1992

Effect of bronchial smooth muscle contraction on lung compliance.

Lung compliance is generally considered to represent a blend of surface and tissue forces, and changes in compliance in vivo are commonly used to indicate changes in surface forces. There are, however, theoretical arguments that would allow contraction of airway smooth muscle to affect substantially the elasticity of the lung. In the present study we evaluated the role of conducting airway contraction on lung compliance in vivo by infusing methacholine (MCh) at a constant rate into the bronchial circulation. With a steady-state MCh infusion of 2.4 micrograms/min into the bronchial perfusate (perfusate concentration = 0.7 microM), there was an approximate doubling of lung resistance and a 50% fall in dynamic compliance. There were also significant decreases in chord compliance measured from the quasi-static pressure-volume curves and in total lung capacity and residual volume. When the same infusion rate was administered into the pulmonary artery, no changes in lung mechanics were observed. These results indicate that the conducting airways may have a major role in regulating lung elasticity. This linkage between airway contraction and lung compliance may account for the common observation that pharmacological challenges given to the lung usually result in similar changes in lung compliance and airway conductance. Our results also suggest the possibility that the lung tissue resistance, which dominates the measurement of lung resistance in many species, might in fact reflect the physical properties of conducting airways.

Airway Resistance↗
PubMed1992

Quantitative evaluation of pulmonary stretch receptor activity during high-frequency ventilation.

The purpose of this study was to determine the neural output of pulmonary stretch receptors (PSRs) in response to conditions that, in previous studies (J. Appl. Physiol. 65: 179-186, 1988 and Respir. Physiol. 80: 307-322, 1990), produced apnea in anesthetized cats. These conditions included changes in airway pressure (Paw; 2 or 6 cmH2O), stroke or tidal volume (1-4 ml/kg), frequency [conventional mechanical ventilation (CMV) vs. high-frequency ventilation (HFV) at 10, 15, and 20 Hz], and levels of inspired CO2 (0, 2, and 5%). These data were needed to assess properly the specific contribution of the PSRs to the apnea found with certain combinations of the above variables. Each PSR was subjected to HFV over a range of mechanical and chemical settings, and its activity was recorded. PSRs exhibited continuous activity associated with pump stroke in 11 of 12 fibers tested. PSRs fired more rapidly when mean Paw was 6 cmH2O [45.3 +/- 0.8 (SE) impulses/s] than when it was 2 cmH2O (31.7 +/- 0.9 impulses/s, P = 0.0001). At both pressures, PSR activity increased as the volume of inflation, or tidal volume, was increased from 1 to 4 ml/kg. At Paw of 2 cmH2O, the number of impulses per second for HFV was not different from that for CMV (averaged over the respiratory cycle), under conditions previously demonstrated as apneogenic for both modes of ventilation. Therefore the absolute amount of information being sent to the brain stem processing centers via PSRs during HFV did not differ from that during CMV. Thus any PSR contribution to HFV-induced apnea must have been the result of changes in the pattern of the signal or the central nervous system's processing of it rather than an increase in the amount of inhibitory afferent signal.

Animals↗
PubMed1992

Antagonists of EDRF attenuate acetylcholine-induced vasodilation in isolated hamster lungs.

To evaluate the role of endothelium-dependent relaxing factor (EDRF) in acetylcholine- (ACh) induced vasodilation in the intact pulmonary circulation, we examined the effects of atropine and three EDRF antagonists that have been shown to be effective in vitro: nitro-L-arginine (NOARG), hemoglobin (Hb), and methylene blue (MB). We studied ACh-induced dilation after preconstriction with angiotensin II and prostaglandin F2 alpha (PGF2 alpha) in hamster lungs perfused with Krebs solution containing Ficoll (4 g/dl) and indomethacin (10 microM). In the constricted lungs with no blockers, infusion of ACh (1 microM) decreased the constriction by 67%, and this effect was completely abolished by atropine pretreatment (1 microM). Treatment of hamster lungs with each of the three EDRF blockers, NOARG (30 microM), Hb (10 microM), and MB (250 microM), augmented the pressor responses to angiotensin II and PGF2 alpha. However, NOARG and MB inhibited the ACh-induced dilation by 49 and 60%, respectively, without affecting vasodilatory responses to isoproterenol, an agent that relaxes vascular smooth muscle independent of EDRF synthesis. In contrast, Hb significantly inhibited both ACh- and isoproterenol-induced vasodilations. Because all these EDRF antagonists attenuated ACh-induced vasodilation in intact hamster lungs, we conclude that EDRF plays a role in this response. Nonselective inhibitory effects of Hb in hamster lungs, however, suggest that mechanisms other than inhibition of EDRF by this agent are also involved.

Acetylcholine↗
PubMed1992

On the purported discovery of the bronchial circulation by Leonardo da Vinci.

Among modern physiologists and anatomists, there has been a nearly universal acceptance that Leonardo da Vinci was the first to identify the anatomy of the bronchial circulation. However, because of certain ambiguities in both his anatomic drawing that was supposed to have shown this circulation and the accompanying descriptive text, we questioned whether he really could have been the first to discover this small but important vasculature. To address this question, we set out to repeat Leonardo's dissections in the ox. We reasoned that perhaps the normally tiny bronchial vessels would be considerably more noticeable in this very large species. Our dissections, however, failed to provide any evidence that Leonardo's drawing was that of the bronchial circulation. Furthermore we observed a set of distinct small pulmonary veins to the left upper and right middle lobes that Leonardo, given his lack of understanding of the function of the lung and its circulation, could have easily mistaken for a separate circulation. We thus conclude that Leonardo da Vinci did not describe the anatomy of the bronchial circulation. We believe that the first person to clearly and unequivocally describe the anatomy of this circulation was the Dutch Professor of Anatomy and Botany, Frederich Ruysch.

Anatomy, Artistic↗
PubMed1992

Pulmonary vascular reactivity and hemodynamic changes in elastase-induced emphysema in hamsters.

Changes in pulmonary hemodynamics and vascular reactivity in emphysematous hamsters were studied in an isolated lung preparation perfused at constant flow with blood and 3% dextran. Hamsters were treated with intratracheal porcine pancreatic elastase at 70 days of age, and experimental studies were conducted at 1, 3, and 8 mo after treatment. Baseline pulmonary arterial pressure in elastase-treated lungs was increased compared with saline-treated control lungs 1 mo after treatment, but this increase did not progress at 3 and 8 mo. Increases in pulmonary arterial pressure in elastase-treated lungs were temporally correlated with the morphological development of emphysema and right ventricular hypertrophy; both of these were evident at 1 mo after treatment and showed little change thereafter. Pressor responses to hypoxia and angiotensin II were not different between elastase-treated and control lungs at 1 and 3 mo. At 8 mo, however, pressor responses in emphysematous lungs to 0% O2 (but not to angiotensin II) were significantly increased. This was the result of a lack of the normal age-related fall in the hypoxic pressor response. Our results suggest that the right ventricular hypertrophy found in these emphysematous animals results from a chronically increased pulmonary vascular resistance. Furthermore, increases in pulmonary vascular resistance in the early development of emphysema are likely a result of the loss of vascular beds and supporting connective tissue.

Angiotensin II↗
PubMed1991

Design and calibration of a high-frequency oscillatory ventilator.

High-frequency ventilation (HFV) is a modality of mechanical ventilation which presents difficult technical demands to the clinical or laboratory investigator. The essential features of an ideal HFV system are described, including wide frequency range, control of tidal volume and mean airway pressure, minimal dead space, and high effective internal impedance. The design and performance of a high-frequency oscillatory ventilation system is described which approaches these requirements. The ventilator utilizes a linear motor regulated by a closed loop controller and driving a novel frictionless double-diaphragm piston pump. Finally, the ventilator performance is tested using the impedance model of Venegas [1].

Calibration↗
PubMed1991

Assessment of pulmonary airway reactivity with high-resolution CT.

The evaluation of airway reactivity plays a central role in the diagnosis of bronchial hyperreactivity and asthma. The authors used high-resolution computed tomography (HRCT) to assess airway reactivity and compared the results with simultaneously performed measurements of airway pressure (Paw). Ten anesthetized and ventilated dogs were studied in a control state, after saline aerosol application, and after histamine aerosol challenge. In each condition, Paw was determined and HRCT was performed at functional residual capacity. On the HRCT scans, the cross-sectional areas of airway lumina were measured by using a computer edging process. After histamine challenge, HRCT demonstrated a decrease in airway areas of 43% +/- 2% (mean +/- standard error) from baseline (control) and Paw increased 99% +/- 18%. Surprisingly, saline aerosol challenge also resulted in a significant decrease in airway areas (26% +/- 3%) from control, while Paw measurements did not change significantly. Airway reactivity varied between dogs and within dogs. The authors conclude that HRCT can depict the site and degree of airway reactions and thus represents a new tool to assess airway reactivity in vivo.

Animals↗
PubMed1991

Use of collateral airways to assess airway reactivity.

We investigated the correlation between collateral airway reactivity and other indexes of lung reactivity in response to aerosol and intravenous (iv) challenges. In four anesthetized mongrel dogs, we measured the peripheral airway resistance (Rp) to gas flow out of a wedged lung segment in different lobes on multiple occasions. We obtained dose-response curves of peripheral airways challenged with iv histamine or aerosols through the bronchoscope. During the same iv bolus challenge, whole lung airway pressure (Paw) responses to histamine were also measured. On separate occasions, changes in lung resistance (RL) were measured after the whole lung was challenged with a histamine aerosol. Reactivity was assessed from the dose-response curves for Rp and RL as the PD50 (dose required to produce a 50% increase); for changes in Paw we calculated the PD15 (dose required to produce a 15% increase over baseline). Results for Rp showed considerably more variability among different lobes in a given animal with the aerosol challenge through the bronchoscope than with the iv challenge. With aerosol challenge there were no significant differences in the mean PD50 for Rp among any of the animals. However, with the iv challenge two of the dogs showed significant differences from the others in reactivity assessed with Rp (P less than 0.01). Moreover, the differences found in the peripheral airways with iv challenge reflected differences found in whole lung reactivity assessed with either iv challenge (Paw vs. Rp, r2 = 0.96) or whole lung aerosol challenge (RL vs. Rp, r2 = 0.84). We conclude that the measurement of the collateral resistance response to iv challenge may provide a sensitive method for assessing airway reactivity.

Aerosols↗
PubMed1991

Measurement of airway wall blood flow in sheep by laser-Doppler flowmetry: interpretation and problems.

We have used laser-Doppler flowmetry (LDF), a technique that detects movement of erythrocytes, to measure tracheal and bronchial wall blood flow in anesthetized open-chest sheep. LDF derives continuous measurements noninvasively, although fiber-optic bronchoscopy is necessary to introduce the LDF probe into the airways. The response of the LDF flow signals at four regions of the airway walls to varying bronchial arterial flow rates was examined in both live and dead sheep by cannulation and subsequent perfusion of the common bronchial artery at different flow rates by use of a roller pump. In the live sheep, variations in bronchial arterial blood flow resulted in variations in LDF signals in the principal bronchus and in lobar and segmental bronchi but not in the trachea. In the dead sheep, variations in bronchial arterial blood flow resulted in variations in LDF signals in all four regions. Within regions, the average response of the LDF signals to varying bronchial blood flow rates was approximately linear in both live and dead sheep, but considerable site-to-site variation in response was observed. In the live sheep, significant LDF signals were observed when the bronchial arterial flow was set to zero and when the bronchial artery was perfused with dextran solution, which would in theory be expected to produce no LDF signal. A small LDF signal was also detected under zero flow conditions in the dead sheep. These observations suggest that the LDF technique, in addition to detecting blood flow from the bronchial artery also detects background noise and/or collateral circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Interaction between CO2 concentration and flow rate on peripheral airway resistance.

In the present study, we investigated the interaction between CO2 concentration and rate of delivered flow on peripheral airway resistance (Rp) in the intact canine lung. Dogs were anesthetized, intubated, paralyzed, and mechanically ventilated with room air to maintain end-tidal CO2 between 4.8 and 5.2%. Using a wedged bronchoscope technique, we measured Rp at functional residual capacity. The relationship between CO2 concentration and Rp was measured at flow rates of 100 and 400 ml/min with 5, 3, 2, 1, and 0% CO2 in air. Measurements were made at the end of a 3-min exposure to each gas. At low flow rates (100 ml/min) responses to hypocapnia were small, whereas at high flow rates (400 ml/min) responses were large. The PC50 (defined as the CO2 concentration required to produce a 50% increase in Rp above baseline Rp established on 5% CO2) at 400 ml/min (1.73%) was significantly larger than that at 100 ml/min (0.38%). We also directly measured the relationship between Rp and flow rate with 5% CO2 (normocapnia) or 1% CO2 (hypocapnia) delivered into the wedged segment. Increases in normocapnic flow caused small but significant decreases in Rp. In contrast, increases in hypocapnic flow from 100 to 400 ml/min caused a 108% increase in Rp. Thus the response to hypocapnia is augmented by increasing flow rate. This interaction can be explained by a simple model that considers the effect of local ventilation-perfusion ratio and gas mixing on the local CO2 concentration at the site of peripheral airway contraction.

Airway Resistance↗
PubMed1991

Role of the epithelium in airway smooth muscle responses to relaxant agonists.

We studied the role of the guinea pig tracheal epithelium in modulating tracheal smooth muscle responses to the relaxant agonists albuterol, sodium nitroprusside, and theophylline. We used an in vitro preparation that allowed separation of the fluids bathing the luminal (internal) and serosal (external) surfaces of the trachea, and bronchodilators were administered to either surface of carbachol-contracted tracheae. All three drugs produced dose-dependent relaxation. However, albuterol and nitroprusside were less potent (concentration that produced half-maximal effect increased by 100- and 32-fold, respectively) when given to the epithelial side with the epithelium intact compared with the epithelium denuded or compared with serosal administration with the epithelium intact. These differences were not observed for theophylline, where smooth muscle responses were independent of either the side of stimulation or of the presence or absence of the epithelium. Direct measurements of the diffusion of theophylline across the tracheal wall in the presence or absence of epithelium showed that after 5 h of incubation with a fixed luminal concentration of theophylline, only 1.7% had diffused across the tracheal wall with the epithelium intact. This increased to only approximately 3.3% when the epithelium was denuded. These results suggest that the epithelial is a relatively weak barrier for lipophilic agents but has a major role as a diffusion barrier to hydrophilic substances.

Albuterol↗