Equine Physiology
Animal Studies:
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- Rats 1: Inhal Toxicol 1999 Mar;11(3):249-64 Adaptive and non-adaptive responses in rats exposed to ozone, alone and in mixtures, with acidic aerosols. Kleinman MT, Mautz WJ, Bjarnason S. Department of Community and Environmental Medicine, University of California, Irvine, CA 92697-1825, USA. mtkleinm@uci.edu Healthy young adult (300 g) Sprague-Dawley rats were exposed for 1-day or 5-day periods, nose only, to purified air (CA) or four different pollutant atmospheres. Pollutant atmospheres included (a) 0.2 ppm ozone; (b) 0.4 ppm O3; (c) a low concentration mixture of ozone and sulfuric acid-coated carbon particles (0.2 ppm, 100 microg/m(3) and 50 microg/m(3), respectively); and (d) a high-concentration O3 and sulfuric acid-coated carbon particle mixture (0.4 ppm, 500 microg/m(3) and 250 microg/m(3), respectively). Following 1-day exposures to the high O3 concentration, significant (p< or =.05) decreases were observed in respiratory tidal volumes and significant increases were observed in lung inflammatory response. Following 5-day exposures to 0.4 ppm ozone, tidal volumes and lung inflammation were not significantly different from those seen in CA controls. In contrast, following 5-day exposures to the high-concentration O3-particle mixture, lung inflammation was increased significantly relative to that seen after 1-day high concentration mixture exposure or after CA exposure. Macrophage Fc-receptor binding, an important immunological function of macrophages, was significantly depressed after 5-day exposures to either the high- or low-concentration O3-particle mixtures compared to 1-day exposures or to CA. Thus, at the concentrations tested, repeated exposures to O3 produced diminished responses in breathing pattern changes and lung parenchymal injuries compared to acute, single exposures. This diminution was not observed after exposures to mixtures of acidic particles plus ozone. We conclude that mixtures of ozone and acidic particles may alter adaptive mechanisms that have been reported by us and others after repeated exposures to ozone alone. PMID: 10380169 [PubMed - indexed for MEDLINE]
1: Arch Toxicol 1998 Jun;72(7):445-9 Chronic exposure to ozone and nitric acid vapor results in increased levels of rat pulmonary putrescine. Sindhu RK, Mautz WJ, Kikkawa Y. Department of Pathology, College of Medicine, University of California at Irvine, 92697-4800, USA. In the past decade, there has been growing public concern for the human health effects of exposure to environmental pollutants. Ozone (O3) is one of the most reactive components of photochemical air pollution. Despite extensive investigations by many laboratories on the functional, biochemical, and cellular effects of O3 exposure in humans, animals, and in vitro systems, questions remain concerning the potential adverse effects to human health represented by chronic near-ambient exposure to this environmental pollutant. In the present investigation, the influence of inhalation of O3 and nitric acid (HNO3) vapor on polyamine levels was examined in rat lungs. Male F344/N rats were exposed nose-only to 0.15 ppm O3 and 50 microg/m3 HNO3 vapor alone and in combination for 4 hours/day. 3 days/week for a total of 40 weeks. At this time the animals were sacrificed and their lungs were examined for polyamine contents. Exposure to O3 and O3 plus HNO3 vapor caused a significant increase in the putrescine content of the lung compared to the air-exposed controls (P < 0.05). The concentrations of pulmonary spermidine and spermine were not significantly increased by exposure to either O3 or HNO3 vapor alone or in combination compared to the air-exposed controls. The role of polyamines in repair and anti-inflammatory processes has been discussed. PMID: 9708884 [PubMed - indexed for MEDLINE]
1: J Toxicol Environ Health 1988;25(2):165-77 Effects of exercise exposure on toxic interactions between inhaled oxidant and aldehyde air pollutants. Mautz WJ, Kleinman MT, Phalen RF, Crocker TT. Department of Community and Environmental Medicine, University of California, Irvine 92717. Respiratory tract injury resulting from inhalation of mixtures of ozone (O3) and nitrogen dioxide (NO2) and of O3 and formaldehyde (HCHO) was studied in Sprague-Dawley rats under exposure conditions of rest and exercise. Focal inflammatory injury induced in lung parenchyma by O3 exposure was measured morphometrically and HCHO injury to the nasal respiratory epithelium was measured by cell turnover using tritium-labeled thymidine. Mixtures of O3 (0.35 or 0.6 ppm) with NO2 (respectively 0.6 or 2.5 ppm) doubled the level of lung injury produced by O3 alone in resting exposures to the higher concentrations and in exercising exposures to the lower concentrations. Formaldehyde (10 ppm) mixed with O3 (0.6 ppm) resulted in reduced lung injury compared to O3 alone in resting exposures, but exercise exposure to the mixture did not show an antagonistic interaction. Nasal epithelial injury from HCHO exposure was enhanced when O3 was present in a mixture. Mixtures of O3 and NO2 at high and low concentrations formed respectively 0.73 and 0.02 ppm nitric acid (HNO3) vapor. Chemical interactions among the oxidants, HNO3, and other reaction products (N2O5 and nitrate radical) and lung tissue may be the basis for the O3-NO2 synergism. Increased dose and dose rate associated with exercise exposure may explain the presence of synergistic interaction at lower concentrations than observed in resting exposure. No oxidation products were detected in O3-HCHO mixtures, and the antagonistic interaction observed in lung tissue during resting exposure may result from irritant breathing pattern interactions. PMID: 3172271 [PubMed - indexed for MEDLINE]
1: J Toxicol Environ Health 1985;16(6):841-54 Enhancement of ozone-induced lung injury by exercise. Mautz WJ, McClure TR, Reischl P, Phalen RF, Crocker TT. Rats were exposed for up to 3.75 h to 0.20-0.80 ppm O3 under conditions of rest and treadmill exercise up to 30 m/min, 20% grade, to assess the importance of exposure duration, O3 concentration, and exercise on lung tissue injury. Focal lung parenchymal lesions increased in abundance and severity in response to the three variables; however, exercise was the most important. Lesion response to exercise was greater than that predicted by a simple proportion to estimated effective dose of O3. The results emphasize the importance of including exercise in assessment of possible adverse health effects of exposure to airborne pollutants. PMID: 4093997 [PubMed - indexed for MEDLINE]
1: Toxicol Appl Pharmacol 1992 Jan;112(1):73-80 Concentration-response relationships of rat lungs to exposure to oxidant air pollutants: a critical test of Haber's Law for ozone and nitrogen dioxide. Gelzleichter TR, Witschi H, Last JA. Department of Internal Medicine, California Primate Research Center, University of California, Davis 95616. Exposure protocols were designed to ask whether lung damage in rats exposed to either ozone or nitrogen dioxide is proportional to dose rate or to cumulative dose. Thus, the response of rats to a constant product of concentration of oxidant air pollutant and time of exposure (C x T) was evaluated for 3-day exposures over a fourfold range of concentrations of ozone (0.2-0.8 ppm) or of nitrogen dioxide (3.6-14.4 ppm) for exposure durations of 6-24 hr per day. The response of rat lungs was quantified by changes in total protein content of lung lavage supernatants or by changes in content of specific cell types in lung lavage pellets. The results of these experiments clearly demonstrate that acute lung damage is a function of cumulative dose (that is, C x T product) for the three highest dose rates tested. However, when exposure duration is extended to include the entire 24-hr period (the lowest dose rate tested), there is a marked attenuation of pulmonary response. Rats were also exposed to mixtures of ozone and nitrogen dioxide with the C x T product held constant. Our results clearly demonstrate that when rats are exposed to combinations of ozone and nitrogen dioxide, lung damage is a function of peak concentration rather than a function of cumulative dose. This deviation from Haber's Law is attributed to a concentration-dependent, synergistic (greater than additive) response to this specific mixture of oxidant air pollutants. PMID: 1733050 [PubMed - indexed for MEDLINE]
1: J Toxicol Environ Health 1987;22(4):417-37 Tracheal and bronchoalveolar permeability changes in rats inhaling oxidant atmospheres during rest or exercise. Bhalla DK, Mannix RC, Lavan SM, Phalen RF, Kleinman MT, Crocker TT. Department of Community and Environmental Medicine, University of California, Irvine 92717. Permeability of tracheal and bronchoalveolar airways of rats was measured and used to examine the effects of inhaled oxidant-containing atmospheres. The atmospheres studied were (a) ozone (O3) at 0.6 ppm (1.2 mg/m3) or 0.8 ppm (1.6 mg/m3); (b) nitrogen dioxide (NO2) at 6 ppm (11.3 mg/m3) or 12 ppm (22.6 mg/m3); (c) O3 + NO2 at 0.6 ppm (1.2 mg/m3) and 2.5 ppm (4.7 mg/m3), respectively; and (d) a 7-component particle and gas mixture (complex atmosphere) representing urban air pollution in a photochemical environment. The rats were exposed for 2 h. The effects of exercise during exposure were evaluated by exposing additional groups in an enclosed treadmill. Exposure of resting rats to 0.8 ppm O3 increased tracheal permeability to DTPA and bronchoalveolar permeability to diethylenetriamine pentaacetate (DTPA) and bovine serum albumin (BSA) at 1 h after the exposure. Bronchoalveolar, but not tracheal, permeability remained elevated at 24 h after the exposure. Exercise during exposure to O3 increased permeability to both tracers in the tracheal and the bronchoalveolar zones, and prolonged the duration of increased permeability in the tracheal zone from 1 h to 24 h, and in the bronchoalveolar zone from 24 h to 48 h. Permeability in the tracheal and bronchoalveolar zones of rats exposed at rest to 6 or 12 ppm NO2 did not differ from controls. However, rats exposed during exercise to 12 ppm NO2 for 2 h developed a significant increase in tracheal and bronchoalveolar permeability to DTPA and BSA at 1 h, but not at 24 or 48 h, after exposure. Exposure at rest to 0.6 ppm O3 plus 2.5 ppm NO2 significantly increased bronchoalveolar permeability at 1 and 24 h after exposure, although exposure at rest to 0.6 ppm O3 alone increased bronchoalveolar permeability only at 1 h after exposure. Exposure to O3 + NO2 during exercise led to significantly greater permeability to DTPA than did exercising exposure to O3 alone. Resting rats exposed to a complex gas/aerosol atmosphere composed of the above O3 and NO2 concentrations, plus 5 ppm (13.1 mg/m3) sulfur dioxide (SO2) and an aerosol of insoluble colloidal Fe2O3 with an aerosol of manganese, ferric, and ammonium salts, demonstrated increased permeability at 1 and 24 h after exposure. Nitric acid vapor was formed in both the O3 + NO2 atmosphere and the complex gas/aerosol atmosphere.(ABSTRACT TRUNCATED AT 400 WORDS) PMID: 3694704 [PubMed - indexed for MEDLINE]
1: J Pharmacol Exp Ther 2000 Dec;295(3):942-50 Long-term exposure to ozone increases acute pulmonary centriacinar injury by 1-nitronaphthalene: II. Quantitative histopathology. Paige RC, Wong V, Plopper CG. Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, California 95616, USA. rcpaige@ucdavis.edu Long-term exposure to the oxidant air pollutant ozone (O(3)) is associated with tolerance to the acute effects of oxidant injury. To test whether this resistance to acute injury extends to bioactivated pulmonary toxicants, male Sprague-Dawley rats were exposed to filtered air (FA) or 0.8 ppm O(3) (8 h/day) for 90 days and administered 1-nitronaphthalene i.p. at doses of 0, 50, or 100 mg/kg. 1-Nitronaphthalene is a pulmonary cytotoxicant requiring metabolic activation. High-resolution histopathology, transmission electron microscopy, and morphometry revealed significantly greater 1-nitronaphthalene toxicity in the central acinar region of O(3)- compared with FA-exposed rats. At 100 mg/kg, injury to terminal bronchioles in O(3)-exposed rats involved denudation of 86% of the basement membrane; 78% of the cells remaining on the epithelium were necrotic. This is compared with denudation of 4% of the basement membrane of FA-exposed rats administered 100 mg/kg 1-nitronaphthalene; only 25% of the cells remaining on the epithelium were necrotic. The key difference between FA- and O(3)-exposed rats treated with 1-nitronaphthalene was the heightened severity of ciliated cell toxicity in O(3)-exposed animals. This is despite the fact that long-term exposure to ozone produces tolerance to oxidant stress in the epithelium of the central acinus. No differences in the susceptibility of intrapulmonary airways or trachea to 1-nitronaphthalene were observed between filtered air- and ozone-exposed rats. This study demonstrates a site-selective synergy between the copollutants ozone and 1-nitronaphthalene in the production of acute lung injury. PMID: 11082427 [PubMed - indexed for MEDLINE]
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- Dogs 1: Res Rep Health Eff Inst 1991 Oct;(45):1-40; discussion 41-50 The effects of exercise on dose and dose distribution of inhaled automotive pollutants. Kleinman MT, Mautz WJ. Air Pollution Health Effects Laboratory, University of California, Irvine 92717. The purpose of this study was to determine how changes in ventilation rate and in the entry route of air pollutants into the respiratory tract (nose versus mouth breathing) affected the respiratory tract uptake and penetration of inhaled gaseous and particulate pollutants associated with automobile emissions. Experiments were performed with female beagle dogs exposed while standing at rest or while exercising on a treadmill at 5 km/hour and a 7.5 percent grade. Dogs were exposed to nitrogen dioxide at concentrations of 1 and 5 parts per million (ppm), to formaldehyde at 2 and 10 ppm, and to an aerosol of ammonium nitrate particles (0.3 micron mass median aerodynamic diameter) at 1 mg/m3. Total respiratory system uptake and effects on breath time, expired tidal volume, fractional expiration time, minute ventilation, respiratory gas exchange, ventilation equivalents for oxygen and carbon dioxide, and dynamic pulmonary resistance and compliance were measured in exercising and resting dogs exposed for two hours to 5 ppm nitrogen dioxide and 10 ppm formaldehyde in combination with 1 mg/m3 of ammonium nitrate particles. Regional penetration of pollutants through oral and nasal airways and pollutant uptake in the lung were measured in a separate group of six tracheostomized dogs standing at rest while being exposed to nitrogen dioxide, formaldehyde, and ammonium nitrate particles. Hypercapnic stimulation was used to modify ventilation rates in the tracheostomized dogs while pollutant penetration and uptake were measured. Dogs exposed to 5 ppm of nitrogen dioxide at rest tended to breathe more rapidly (p less than 0.05) and more shallowly (a nonsignificant trend) than dogs exposed to purified air. The changes observed were similar in direction, but of smaller magnitude, to changes observed when the same dogs were exposed during exercise to ozone at 0.6 ppm in a separate study. Rapid-shallow breathing was not observed when the dogs were exposed during exercise to 5 ppm nitrogen dioxide. Dogs exposed to a mixture of 10 ppm formaldehyde and 1 mg/m3 ammonium nitrate particles during exercise showed a shift to larger tidal volume breathing, but the response was much less pronounced than the slow-deep breathing pattern response observed in a separate study of dogs exposed to 10 ppm formaldehyde alone. The total respiratory system uptake of formaldehyde from the formaldehyde and ammonium nitrate mixture was larger than that measured for 10 ppm of formaldehyde alone in another exercise and exposure study. (ABSTRACT TRUNCATED AT 400 WORDS) PMID: 1722101 [PubMed - indexed for MEDLINE]
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- Primate 1: Am Rev Respir Dis 1988 Feb;137(2):326-30 Airway response to ultra short-term exposure to ozone. Fouke JM, Delemos RA, McFadden ER Jr. Southwest Foundation for Biomedical Research, San Antonio, Texas. To determine whether acute short-term exposure to oxidant pollutants can cause changes in respiratory mechanics, we gave 0.5 ppm ozone for 5 min to 7 baboons. We measured pulmonary resistance (RL) and obtained dose response curves to methacholine before and after the exposures. This brief insult increased resistance (control RL = 1.53 +/- 0.21 cm H2O.L-1 s; post-ozone RL = 3.53 +/- 0.54 cm H2O.L-1 s). On a second occasion, 6 of these animals were restudied before and after the administration of cromolyn sodium. Although this drug had no effect on the measurements of mechanics made in the control period, it significantly reduced the ozone-induced changes in mechanics. The increase in RL was 52% of that produced in the first study. The results demonstrated that the ozone injury with its acute and subacute airway sequelae occurs quite rapidly and after very brief exposure. The time course of the change in mechanics and the effects of cromolyn suggest the hypothesis that surface epithelial cells are disrupted, causing subsequent release of bronchoconstricting agents. PMID: 3124677 [PubMed - indexed for MEDLINE]
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- Horses 1: Equine Vet J Suppl 1999 Jul;30:92-5 Effect of exercise on concentrations of immunoreactive endothelin in bronchoalveolar lavage fluid of normal horses and horses with chronic obstructive pulmonary disease. Benamou AE, Art T, Marlin DJ, Roberts CA, Lekeux P. Centre for Equine Studies, Animal Health Trust, Newmarket, Suffolk, UK. Chronic obstructive pulmonary disease (COPD) represents a major cause of loss of performance in the horse. The role of endothelin (ET), a potent bronchoconstrictive and vasoactive peptide, is currently being investigated in asthma and other obstructive respiratory diseases in man. We have previously found elevated systemic and pulmonary endothelin levels in horses during exacerbation of COPD. In the present study, our aim was to examine possible variations in ET concentrations occurring during exercise in COPD horses. We compared the effects of intense treadmill exercise on the recovery of endothelin (ET) in the bronchoalveolar lavage fluid (BALF) as well as in arterial and venous blood, in a group of 5 healthy horses and a group of 5 COPD horses studied alternately in remission and while symptomatic. We also investigated the possible correlations between ET levels and pulmonary function tests during the study. While exercise did not affect the ET levels recovered in BALF among controls, it caused a significant increase (P = 0.02) among symptomatic COPD horses. During remission, wide variations of ET levels among horses, at rest and during exercise, made any significant interpretation difficult. No correlation could be found between exercise-induced changes in ET concentrations and pulmonary function tests or changes in arterial oxygen tension with exercise. We conclude that exercise appears to affect the release of ET by the airways in COPD horses, in contrast to healthy horses. It is still unclear, however, whether these differences relate to adjustments of lung function during exercise. PMID: 10659230 [PubMed - indexed for MEDLINE]
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