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Biomedical subjects

M J Hazucha

Publications and source records attributed to M J Hazucha.

At least 19 recordsLinked to original sources
PubMed2000

Noninvasive ambulatory assessment of cardiac function in healthy men exposed to carbon monoxide during upper and lower body exercise.

Very little is known about the cardiovascular responses of exercising individuals when exposed to carbon monoxide (CO). Sixteen healthy nonsmoking men aged 18-29 years participated in the study. Using a combination of exposures to CO by breathing from a bag or in an environmental chamber, subjects performed a randomized sequence of brief (5 min) multi-level treadmill and hand-crank exercises on different days at less than 2% carboxyhemoglobin (COHb) and after attaining target levels of 5%, 10%, 15%, and 20% COHb. To assess cardiac function changes we employed noninvasive impedance cardiography (ICG) and three-lead electrocardiograms (ECG). The ICG was used to estimate cardiac output, stroke volume, heart rate, cardiac contractility, and time-to-peak ejection time. The ECG was used to assess myocardial irritability and ischemia, and changes in cardiac rhythm. The results showed that the cardiovascular system compensated for the reduced O2-carrying capacity of the blood by augmenting heart rate, cardiac contractility, and cardiac output for both upper-body and lower-body exercise. While this mechanism served well in submaximal exercise, the enhanced cardiovascular response to exercise was not without physiological costs because it began to fail at moderate levels of CO exposure and exercise. We concluded that young, apparently healthy men can perform submaximal upper and lower-body exercise without overt impairment of cardiovascular function after CO exposures attaining 20% COHb.

Adolescent↗
PubMed2000

Time course of response to ozone exposure in healthy adult females.

Ozone exposure causes acute decrements in pulmonary function, increases airway responsiveness, and changes the breathing pattern. We examined these responses in 19 ozone-responsive (DeltaFEV(1) > 5%) young females exposed to both air and 0.35 ppm ozone. The randomized 75-min exposures included two 30-min exercise periods at V(E) approximately 40 L/min. Responses were measured before, during, and after exposure and at 18 and 42 h postexposure. FVC, FEV(1), and FIV(0.5) decreased (p <.01) immediately postexposure by 13.2%, 19.9%, and 20.8%, respectively, and the airway responsiveness was significantly increased. Raw increased (p <.05), while TGV remained essentially unchanged. At 18 h postexposure, the airways were still hyperresponsive and FEV(1) and FIV(0.5) were still 5% below the preexposure levels. There were no residual effects in any of the variables at 42 h postexposure. During exercise in ozone the tidal volume was decreased (-14%) and respiratory frequency increased (+15%). The changes in airway responsiveness were not related to changes in spirometric measurements. We found no significant differences between postair and postozone mouth occlusion pressure (Pm(0.1)) and the hypercapnic response to CO(2) rebreathing. We conclude that ozone induced typical acute changes in airway responsiveness and that ventilatory (exercise), spirometric (inspiratory and expiratory), and plethysmographic pulmonary function may show some residual effects for up to 18 h after exposure. The ozone-induced alteration in breathing pattern during exercise does not appear to be related to a change in ventilatory drive.

Administration, Inhalation↗
PubMed1998

Nociceptive mechanisms modulate ozone-induced human lung function decrements.

We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535-1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18-59 yr) known to be "weak" (WR; n = 20) and "strong" O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0. 42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 microgram/kg iv) or saline. O3 exposure significantly (P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma beta-endorphin levels were not related to an individual's O3 responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3 responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.

Adolescent↗
PubMed1996

Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation and lung function changes.

Inhalation of O3 causes airways neutrophilic inflammation accompanied by other changes including increased levels of cyclo-oxygenase products of arachidonic acid in bronchoalveolar lavage fluid (BALF). Ozone O3 exposure also causes decreased forced vital capacity (FVC) and forced expiratory volume after 1 s (FEV(1)), associated with cough and substernal pain on inspiration, and small increases in specific airway resistance (SRAW). The spirometric decrements are substantially blunted by pretreatment with indomethacin. Since the O3-induced decrement in FVC is due to involuntary inhibition of inspiration, a role for stimulation of nociceptive respiratory tract afferents has been suggested and cyclo-oxygenase products have been hypothesized to mediate this stimulation. However, the relation (if any) between the O3-induced neutrophilic airways inflammation and decreased inspiratory capacity remains unclear. We studied the effects of pharmacologic inhibition of O3-induced spirometric changes on the inflammatory changes. Each of ten healthy men was exposed twice (5-week interval) to 0.4 ppm O3 for 2 h, including 1 h of intermittent exercise (ventilation 601*min(-1)). One-and-a-half hours prior to and midway during each exposure the subject ingested 800 mg and 200 mg, respectively, of the non-steroidal anti-inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in randomized, double-blind fashion. Spirometry and body plethysmography were performed prior to drug administration, and before and after O3 exposure. Immediately following postexposure testing, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed. Neither IBU nor PLA administration changed pre-exposure lung function. O3 exposure (with PLA) caused a significant 17 percent mean decrement in FEV(1) (P <0.01) and a 56 percent increase in mean SRAW. Following IBU pretreatment, O3 exposure induced a significantly lesser mean decrement in FEV(1) (7 percent) but still a 50 percent increase in mean SRAW. IBU pretreatment significantly decreased post-O3 BAL levels of prostaglandin E2 (PGE2) by 60.4 percent (P <0.05) and thromboxane B(2) (TxB(2)) by 25.5 percent (P <0.05). Of the proteins, only interleukin-6 was significantly reduced (45 percent, P <0.05) by IBU as compared to PLA pretreatment. As expected, O3 exposure produced neutrophilia in BALF. There was, however, no effect of IBU on this finding. None of the major cell types in the BALF differed significantly between pretreatments. We found no association between post-exposure changes of BALF components and pulmonary function decrements. We conclude that IBU causes significant inhibition of O3-induced increases in respiratory tract PGE(2) and TxB(2) levels concomitant with a blunting of the spirometric response. This is consistent with the hypothesis that the products of AA metabolism mediate inhibition of inspiration. However, IBU did not alter the modest SRAW response to O3.

Adult↗
PubMed1994

Prediction of carboxyhemoglobin formation due to transient exposure to carbon monoxide.

Fifteen men were exposed to 6,683 ppm C18O for 3.09-6.65 min. Arterial and antecubital vein blood samples were drawn at 1-min intervals beginning at the start of C18O inhalation and ending 10 min later. Simultaneously, alveolar ventilation was calculated from the measured values of minute ventilation and dead space. All other parameters of the Coburn-Forster-Kane equation (CFKE), except the Haldane affinity ratio, were measured separately in each subject. Means of CFKE predictions of increases in venous HbCO (delta HbCO) in samples collected approximately 2 min after cessation of exposure were accurate, but the range in errors of prediction for individual subjects was +/- 3.8% HbCO, depending on the time after exposure cessation. Increases in venous and arterial HbCO were inaccurately predicted during and immediately after HbCO formation, however. Venous blood was overestimated during CO uptake because of a delayed appearance of HbCO. Individual subjects differed markedly in the degree of delay of HbCO appearance in venous blood. Arterial delta HbCO was consistently underestimated either by the CFKE or by predictions based on venous blood samples. Thus, exposure of such organs as brain or heart to HbCO may be substantially higher than expected during transient high-level CO exposure.

Adolescent↗
PubMed1994

Effect of regional circulation patterns on observed HbCO levels.

In an earlier experiment, we briefly exposed 15 young men to high levels of CO while simultaneously monitoring arterial and peripheral venous HbCO levels. The arterial HbCO levels were considerably higher than the venous levels during the CO exposure. Furthermore, great variation in the difference between arterial and venous HbCO levels was observed, with the maximal difference for each subject ranging from 2.3 to 12.1% HbCO. In the present paper, we suggest an explanation for the observed differences between arterial and venous HbCO on the basis of the regional circulation of the forearm, where both samples were taken. Because regional circulation patterns are known to vary with physical training, the differences in physical training between subjects may account for the observed variation. An expanded model was derived from the Coburn-Forster-Kane equation, which reflects the above hypothesis. Most of the parameter values for the expanded model were measured on individual subjects. Literature values were used for other parameters. Two parameters were estimated using five of the subjects and were then used in the predictions of the expanded model for the remaining subjects.

Arteries↗
PubMed1994

Lung function response of healthy women after sequential exposures to NO2 and O3.

Since NOx emissions bear a precursor-product relation with ambient ozone (O3) levels, the sequence of peak ambient concentrations is first nitrogen dioxide (NO2) followed later in the day by ozone (O3). We ascertained whether preliminary exposure to 0.6 parts per million (ppm) NO2 would affect the lung function response to subsequent exposure to 0.3 ppm O3. Twenty-one healthy young nonsmoking women (18 to 35 yr of age) underwent two sets of exposures on two different days separated by a minimum of 2 wk. On one day, subjects were exposed to air for 2 h followed 3 h later by a 2-h exposure to O3. On the other day, the first exposure was to NO2; order of the days was randomized. During each exposure subjects intermittently exercised, alternating 15 min of rest with 15 min of exercise (Ve approximately 40 L/min). Spirometry was performed before the first exposure and at 1-h intervals until the end of the 2-h (O3) exposure. Plethysmography measurements were made before and after NO2 and O3 exposures. Nonspecific airway reactivity (AR) was determined at least 1 wk prior to the first exposure and following each O3 exposure. AR to methacholine (MCh) was expressed as dose required to decrease FEV1 by 10% (PD10FEV1). Nitrogen dioxide exposure alone did not reduce FEV1 but did significantly enhance O3-induced spirometric changes. No significant effects were observed in plethysmography. On both exposure days, the median PD10FEV1 was significantly reduced (p < 0.05) from control PD10FEV1 (14.3 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of steady-state and variable ozone concentration profiles on pulmonary function.

Measurements of ambient ozone (O2) concentration during daylight hours have shown a spectrum of concentration profiles, from a relatively stable to a variable pattern usually reaching a peak level in the early afternoon. Several recent studies have suggested that in estimating exposure dose (O3 concentration [C] x exposure time [T] x ventilation [V]), O3 concentration needs to be weighted more heavily than either ventilation or duration of exposure in the estimates. In this study we tested the hypothesis that regardless of concentration pattern and exposure rate the same exposure dose of O3 will induce the same spirometric response. We exposed 23 healthy male volunteers (20 to 35 yr of age) for 8 h to air, 0.12 ppm O3 (steady-state), and a triangular exposure pattern (concentration increased steadily from zero to 0.24 ppm over the first 4 h and decreased back to zero by 8 h). During the first 30 min of each hour, subjects exercised for 30 min at minute ventilation (VE) approximately 40 L/min. The order of the exposures was randomized, and the exposures were separated by at least 7 days. The response patterns over the 8-h periods for spirometric variables in both O3 exposures were statistically different from air exposure changes and from each other. For FEV1 the p values were 0.017 between air and steady-state profile, 0.002 between air and triangular profile, and 0.037 between steady-state and triangular profiles. Although in the triangular pattern of exposure the maximal O3 concentration was reached at 4 h, the maximum FEV1 decrement (10.2%) was observed at 6 h of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Mechanism of action of ozone on the human lung.

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Relationship between ozone exposure and pulmonary function changes.

A detailed comparison of literature-reported averaged decrements in pulmonary function of normal subjects exposed to O3 has been undertaken. The data base was formed by including data published during the past 20 yr from studies that reported at least one of the pulmonary function variables (forced vital capacity, forced expiratory volume at 1 s, mean forced expiratory flow between 25 and 75% of forced vital capacity, and airway resistance) acquired at 2 h of exposures utilizing either original or modified Bates-Hazucha (intermittent exercise) protocol and that satisfied selection criteria. The final set of data (24 studies involving 299 subjects) was divided by ventilation rate (exercise loads) into four categories: light, moderate, high, and very high ventilation level. For each pulmonary function variable and ventilation level a quadratic function has been fitted to the data using regression procedures. The curve parameter estimates have been computed, tabulated, and statistically evaluated. The slope (quadratic coefficient) for each variable within a group and almost all variables between groups were significantly different from zero and from each other at P less than or equal to 0.0001.

Forced Expiratory Flow Rates↗
PubMed1987

Differing response of asthmatics to sulfur dioxide exposure with continuous and intermittent exercise.

Ten subjects with mild asthma were initially exposed in an environmental chamber (26 degrees C 70% relative humidity) to clean air and 1.0 ppm SO2 while performing 3 sets of 10-min treadmill exercises (ventilation, 41 L/min) broken by 15-min rest periods. To evaluate the effects of the pattern and duration of exercise on the response to SO2 exposure, the subjects were then exposed to the same environmental conditions while exercising continuously for 30 min. Specific airway resistance (SRaw) was measured by body plethysmography before each exposure and after each exercise. All SO2 responses were significantly greater than the clean air responses. With intermittent exercise and SO2 exposure, mean SRaw measurements (preexposure and after 10, 20, and 30 min of exercise) were 5.4, 14.7, 12.8, and 11.1 cm H2O/s. After SO2 exposure with continuous exercise, the mean SRaw showed an increase from 5.2 to 17.3 cm H2O/s. This increase was significantly (p = 0.018) greater than the response after the third exercise in the intermittent protocol. It appears that asthmatics show an attenuated response to repetitive exercise in an atmosphere of 1.00 ppm SO2 and that the response to SO2 exposure develops rapidly and is maintained during 30 min of continuous exercise.

Adult↗
PubMed1987

An aerosol generator system for inhalation delivery of pharmacologic agents.

Most commercially available aerosol generators widely used in medical applications produce aerosols characterized by a large mass median diameter in the 4-8 micron range and the particle size in the 0.1-10.0 microns range. The desirable size of therapeutic and diagnostic aerosols, however, is about 2-4 microns mass median diameter, and less than 2.0 geometric standard deviation; this size increases the reproducibility of inhalation tests and enhances drug efficacy. We combined the commercially available DeVilbiss Model 65 nebulizer with a dilution/mixing chamber developed in our laboratory. The characteristics of this aerosol generator system were examined over a range of operating conditions and concentrations of solutions of three bronchoconstrictive agents--histamine, carbachol, and methacholine. The aerosol generator system produced a polydispersed aerosol with a mass median diameter range of 1.7-2.4 microns and geometric standard deviation of 1.5. The reliable and reproducible operation of the aerosol generator system greatly increases the power of bronchial challenge tests with bronchoconstrictive drugs.

Administration, Inhalation↗
PubMed1985

Responses of subjects with chronic obstructive pulmonary disease after exposures to 0.3 ppm ozone.

We previously reported (American Review of Respiratory Disease 1982; 125:664-669) that the respiratory mechanics of intermittently exercising persons with chronic obstructive pulmonary disease (COPD) were unaffected by a 2-h exposure to 0.2 ppm ozone. Employing a single-blind, cross-over design protocol, 13 white men with nonreversible COPD (9 current smokers; mean FEV1/FVC, 56%) were randomly exposed on 2 consecutive days for 2 h to air and 0.3 ppm ozone. During exposures, subjects exercised (minute ventilation, 26.4 +/- 3.0 L/min) for 7.5 min every 30 min; ventilation and gas exchange measured during exercise showed no difference between exposure days. Pulmonary function tests (spirometry, body plethysmography) obtained before and after exposures were unchanged on the air day. On the ozone day the mean airway resistance and specific airway resistance showed the largest (25 and 22%) changes (p = 0.086 and 0.058, respectively). Arterial oxygen saturation (SaO2) obtained in 8 subjects during the last exercise interval showed a mean decrement of 0.95% on the ozone exposure day; this change did not attain significance (p = 0.074). Nevertheless, arterial oxygen desaturation may be a true consequence of low-level ozone exposure in this compromised patient group. As normal subjects undergoing exposures to ozone with slightly higher exercise intensities show a threshold for changes in their respiratory mechanics at approximately 0.3 ppm, our data indicate that persons with COPD are not unduly sensitive to the effects of low-level ozone exposure.

Aged↗
PubMed1983

Effects of 0.1 ppm nitrogen dioxide on airways of normal and asthmatic subjects.

It has been reported (J. Clin. Invest. 57: 301-307, 1976) that inhalation of nitrogen dioxide (NO2) will enhance the bronchial reactivity of asthmatics. This study was designed to evaluate the respiratory effect of a 1-h exposure of normal subjects and of atopic asthmatics to 0.1 parts per million (ppm) NO2. Fifteen normal and 15 asthmatic subjects were exposed to air and to NO2 in a randomized double-blind crossover design. Exposure to either atmosphere was bracketed by bronchial inhalation challenge using aerosolized metacholine chloride solutions. Plethysmographic measurements of specific airway resistance (sRaw) and the forced random noise impedance spectrum (5-30 Hz) were obtained immediately after each methacholine dose. Following acute exposure to NO2, there was a slight but not significant increase in mean base-line sRaw in both normals and asthmatics. The overall base-line resistive properties of the respiratory system determined by forced random noise excitation were not significantly affected by NO2 inhalation either. Finally, there was no change in bronchial response to methacholine challenge in either group. These findings indicate that 0.1 ppm NO2 exposure for 1 h without exercise had no demonstrable airways effects in either young atopic asthmatics with mild disease or young normal subjects.

Adolescent↗
PubMed1983

Pulmonary effects of ozone exposure during exercise: dose-response characteristics.

Because minimal data are available regarding the pulmonary effects of ozone (O3) at levels less than 0.27 ppm, six groups of healthy young males were exposed for 2.5 h to one of the following O3 concentrations: 0.0, 0.12, 0.18, 0.24, 0.30, or 0.40 ppm. Fifteen-minute periods of rest and exercise (65 l/min minute ventilation) were alternated during the first 2 h of exposure. Coughing was observed at all levels of O3 exposure. Small changes in forced-expiratory spirometric variables [forced vital capacity (FVC), forced expiratory volume in 1 s, and mean expiratory flow rate between 25 and 75% FVC] were observed at 0.12 and 0.18 ppm O3, and larger changes were found at O3 levels greater than or equal to 0.24 ppm. Changes in tidal volume and respiratory frequency during exercise, specific airway resistance, the presence of pain on deep inspiration, and shortness of breath occurred at O3 levels greater than or equal to 0.24 ppm. In conclusion, pulmonary effects of O3 were observed at levels much lower than that for which these effects have been previously described. Stimulation of airway receptors is probably the mechanism responsible for the majority of observed changes; however, the existence of a second mechanism of action is postulated.

Adolescent↗
PubMed1982

The acute effects of 0.2 ppm ozone in patients with chronic obstructive pulmonary disease.

Epidemiologic data suggest that patients with chronic obstructive pulmonary disease (COPD) might be more sensitive than normal persons to the respiratory effects of oxidant pollutant exposure. Our study was designed to determine the response of patients with COPD to ozone. Thirteen white men with nonreversible airways obstruction (mean FEV1/FVC, 58%), of whom 8 were current smokers, were randomly exposed for 2 h to air and to 0.2 ppm ozone on 2 consecutive days using a single-blind crossover design. During either exposure, subjects exercised for 7.5 min every 30 min. Measures of respiratory mechanics obtained pre-exposure and postexposure were not significantly affected by either exposure. Similarly, ventilation and gas exchange measured during exercise showed no difference either between exercise periods or exposure days. However, arterial O2 saturation (SaO2), measured by ear oximetry during the final exercise period each day was lower (94.8%) at the end of O2 exposure, than SaO2 obtained at the end of air exposure (95.3%), the difference (0.48%) being significant (p = 0.008). Because normal subjects undergoing comparable exposures show a threshold for respiratory mechanical effects at about 0.3 ppm ozone, our data suggest that mild to moderate COPD is not associated with increased sensitivity to low ozone concentrations. However, our data do not rule out the possibility that the response of such subjects might be exaggerated at higher ozone concentrations. The consistent (in 11 of 13 subjects), though small, decrease in SaO2 may indicate that indexes of ventilation/perfusion distribution might be more sensitive measures of ozone effect in this compromised patient group than are conventional respiratory mechanics measures.

Adult↗
PubMed1981

Correlation of airway resistance with forced random noise resistance parameters.

The correlation between airway resistance (Raw) measured in a plethysmograph and three respiratory resistance parameters measured by forced random noise was evaluated. Forced random noise resistance parameters were the average resistance between 5 and 9 hz (R5-9), the average resistance between 20 and 24 Hz (R20-24), and the extrapolated resistance at 1 Hz (R1). We studied 22 healthy, nonsmoking subjects, 10 of whom had a history suggesting childhood asthma. Serial measurements were made after inhalation of aerosols containing increasing concentrations of methacholine of aerosols containing increasing concentrations of methacholine to obtain data in various stages of bronchoconstriction. There was a broad range of responsiveness to methacholine; the ratio of the peak to base-line values of Raw ranged from 1.1 to 6.3. R1, R5-9, and R20-24 were related to Raw by linear regression analysis. R1 and R5-9 showed excellent correlation with Raw (r = 093 and 4=0.91, respectively); R20-24 showed much poorer correlation (r = 0.62). The slopes of the regression equations for R1 and R5-9 were 1.56 and 0.51, respectively; thus neither provided an exact measure of Raw. The data appear to be consistent with a model in which most of the methacholine-induced increase in resistance occurred in the peripheral airways and only a small fraction in the central airway.

Adolescent↗