Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Furoyl saccharin was evaluated for its ability to prevent the development of emphysematous lesions produced in hamsters by the exposure to aerosolized papain (3% for 3 h). Pretreatment with intratracheal furoyl saccharin (at the doses of 0.3, 1, 3 mg) reduced the appearance of papain-induced emphysema as evaluated by both physiologic (static compliance) and histologic (mean linear intercept and internal surface area of the lungs) methods. Inhibition was dose-related with maximal reduction of changes in static compliance (74%), mean linear intercept (84%) and internal surface area (65%) observed after a dose of 3 mg. This is the first time that a non-peptide acylating inhibitor of serine proteases is reported to be affective in preventing the development of experimental emphysema.
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PMID:The effect of furoyl saccharin, a novel non-peptidic acylating protease inhibitor, on experimental emphysema in the hamster. 401 80

We examined the changes in vascular and interstitial mechanics in pulmonary emphysema (PE) using a canine lobar model. PE was produced in the left lower lobe (LLL) of five dogs (group E) by six weekly intrabronchial instillations of the enzyme papain. In five control dogs (group C), a normal saline solution was used. In our in vivo preparation, vascular flow (Q) to the LLL was measured. Inflow (Ppa) and outlow (Pv) pressures to the LLL could be varied independently. The relationship of Ppa to Q was examined in zones 2 and 3 of West. The slope of the Ppa-Q relationship was used to determine vascular conductance, whereas the extrapolation to zero flow in zone 2 conditions represented the mean pressure required for vascular recruitment (Pi). Lobar weight gain was measured continuously. Following step increases in Ppa, the rapid increase in wet weight measured when Q to the LLL was zero was used to obtain vascular compliance (C). Subsequent slow increases in wet weight were used to determine the rate of fluid exchange with the interstitium (Qf). The slope of the Qf-Ppa relationship represented fluid conductance (Kf). The extrapolation to zero Qf gave the minimal pressure required for continuous edema formation (Pm). Compared with group C, vascular conductance (G) decreased and Pi increased in group E, whereas fluid conductance (Kf) and Pm increased. The decrease in G most likely resulted from the loss of vascular cross-sectional area in emphysematous lungs, whereas the increase in Pi was possibly due to mechanical changes in the lung interstitium which increased vessel closure. We propose that the increase in Kf in group E reflected an increase in interstitial conductance, such that due to structural changes in the interstitium in emphysematous lungs, tissue resistance to fluid flux decreased.
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PMID:Vascular and interstitial mechanics in canine pulmonary emphysema. 407 78

Intrapulmonary deposition of the proteolytic enzyme papain produces a lesion resembling emphysema in experimental animals. The natural history of this lesion has not been well defined. The present study was performed to evaluate changes in lung structure and function with aging in normal rats and rats exposed to an aerosol of papain at 2 mo of age. Groups of control and papain-exposed animals were studied at 4, 8, and 18 mo of age. The parameters of lung function studied were specific airways' conductance (G(aw)/TGV), diffusing capacity per unit of alveolar volume (D(Lco)/V(A)), diffusing capacity (D(Lco)), and functional residual capacity (FRC). Morphometric parameters were the postfixation lung volume (V(L)) and mean chord length (L(M)); internal surface area (ISA) and ISA extrapolated to both the mean V(L) of the corresponding papain group and a V(L) of 10 ml (ISA(10)) were calculated. At 4 mo of age L(M) and FRC were significantly increased and ISA, D(Lco)/V(A), and D(Lco) were significantly reduced in the papain group. At 8 mo of age L(M) was significantly increased and ISA was significantly decreased in the papain group: physiologic studies were not performed in this group. At 18 mo of age L(M) was significantly increased and D(Lco)/V(A), D(Lco), and ISA were significantly decreased. Neither progression nor healing of the lesion was observed despite similar lung growth in both groups. This study demonstrates that a single proteolytic lung injury produces a fixed deficit of lung parenchyma. Progressive lung destruction may require repeated or continuous lung injury.
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PMID:Lung structure and function with age in normal rats and rats with papain emphysema. 474 15

Rats were exposed for 7 days to an oxygen concentration of 85% and then submitted to an aerosol of papain, immediately, 3, 7 or 15 days after this exposure. The number of animals dying increased as the time between the administration of papain and the end of the exposure to oxygen increased. The quantification of emphysema was made by measurement of the mean linear intercept (LM). The LM does not differ between animals pretreated with oxygen and which have received papain, immediately or after 3 days, and the controls in air not having received papain. On the contrary, the animals pretreated with oxygen and having received papain 7 or 15 days later show a significantly higher LM than do the controls in air having received papain. The protection of the lung against the elastolytic effect of papain by a preliminary stay in 85% O2 is short-term; its mechanism is discussed.
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PMID:Papain-induced emphysema: the influence of preliminary oxygenation. 622 62

In the hearts of control beagle dogs, capillary density in the right ventricle was found to be similar to that of the subendocardium of the left ventricle but lower than that of the subepicardium of the left ventricle. In emphysematous animals, 6 months after the exposure to papain (the emphysema-inducing agent), capillary density in the right ventricle and in the subendocardium of the left ventricle increased significantly, reaching values similar to that of the subepicardium of the left ventricle, which remained constant. These morphologic changes are considered to be an adaptation to a prolonged condition of increased myocardial oxygen demand and/or may represent an early stage of a developing cardiac hypertrophy.
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PMID:Increased myocardial capillary density in dogs with experimental emphysema. 623 25

Chronic hypoxic lung diseases are associated with abnormal blood pressure regulation. Because the lung is the principal site of angiotensin conversion and because hypoxia decreases converting enzyme activity, we examined whether angiotensin converting enzyme activity was impaired in lung disease. 12 dogs received a 6 wk course of aerosolized and intratracheal papain that produced moderate panlobular emphysema. These dogs and 24 control dogs were anesthetized and sampling catheters were placed under fluoroscopic control. Angiotensin conversion was measured by a blood pressure response bioassay. Pulmonary converting enzyme activity was also assessed by infusing bradykinin (BK) and using radioimmunoassay to measure the instantaneous clearance of BK and the concentration of BK in the pulmonary artery which first produced spillover of BK into left atrial blood. Angiotensin conversion was reduced in the emphysematous dogs to 81.1% (13.2 SD) from 92% (6 SD) in the control dogs (P < 0.01). Instantaneous clearance of BK in the emphysematous dogs was only slightly reduced (93%), despite reduction in their Pao(2) to 75 mm Hg, indicating that the greatest proportion of the perfused vascular bed was exposed to alveolar Po(2) of >90 mm Hg. However, the barrier to BK passage provided by the lung, and measured by the spillover level, was reduced (1/4) to (1/2) that observed in control animals. That the defect was promptly corrected by supplemental oxygen indicates that regional pulmonary vascular converting enzyme activity had been impaired by regional alveolar hypoxia, which permitted some peptide to pass through the lungs unmetabolized. Determination of peptide metabolism in the lungs may provide a useful measure of regional alveolar hypoxia and may lead to new ways of assessing lung injury.
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PMID:Impaired angiotensin conversion and bradykinin clearance in experimental canine pulmonary emphysema. 625 12

The pathophysiology of reduced maximum expiratory flow in a canine model of pulmonary emphysema was studied, and the results interpreted in terms of the wave-speed theory of flow limitation. According to this theory, maximum expiratory flow is related both to the cross-sectional area and compliance at an airway site where a critical gas velocity is first reached ("choke-point") and to gas density. Pulmonary emphysema was produced by the repeated instillations of the enzyme papain into the airways of six dogs. In five control dogs, a saline solution was instilled. During forced vital capacity deflation, in an open-chest preparation, maximum expiratory flow, choke-point locations, and the response to breathing an 80:20 helium/oxygen gas mixture were determined at multiple lung volumes. To locate choke-points, a pressure measuring device was positioned in the airway to measure lateral and end-on intrabronchial pressures, from which the relevant wave-speed parameters were obtained. In general, the reduced maximum expiratory flow in emphysema can be explained by diminished lung elastic recoil pressure and by altered bronchial pressure-area behavior, which results in a more peripheral location of choke-points that have smaller cross-sectional areas than controls. With respect to the density dependence of maximum expiratory flow, this response did not differ from control values in four dogs with emphysema in which frictional pressure losses upstream from choke-points did not differ on the two gas mixtures. In two dogs with emphysema, however, upstream frictional pressure losses were greater on helium/oxygen than on air, which resulted in a smaller cross-sectional area on helium/oxygen; hence density dependence decreased.
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PMID:Expiratory flow limitation and the response to breathing a helium-oxygen gas mixture in a canine model of pulmonary emphysema. 671 39

Emphysema was induced in mongrel dogs by four weekly inhalations of papain. The effects of IPPV were studied using four different inspiratory flow waveforms and each at three different inspiratory times. Tidal volume and respiratory frequency were kept constant and inspiratory time and flow waveform were varied independently. There were statistically significant differences in a number of physiological variables. With a longer inspiratory time of 2.2s and with the reversed ramp flow waveform VD/VT was decreased. With the reversed ramp flow waveform there was a greater total compliance, increased (PAo2-Pao2) and reduced PaCO2. There were statistically significant differences in mean airway and oesophageal pressures which indicate valid differences in the flow waveforms and times.
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PMID:Effects of varying inspiratory flow waveform and time in intermittent positive pressure ventilation: emphysema. 680 17

The development of papain-induced emphysema and the effect of structural changes of the lung on pulmonary hemodynamics were investigated in the dog in a 6-month study. Papain was administered as an aerosol at the beginning of the study and at Day 21; control animals received saline. At 3 or at 6 months, hemodynamic investigations were carried out in the awake animal (sedated with piritramide). The dogs were then killed and the lungs processed for morphometric evaluation. Arterial blood gases were analyzed at regular intervals for the duration of the study. In the papain-treated dogs, mean linear intercept (Lm) and internal surface area of the lungs corrected to an arbitrary lung volume of 2L (ISA2) were significantly different from control dogs both at 3 and at 6 months. No progression of the structural changes of the lung occurred between these two time intervals. Arterial blood oxygenation was normal throughout the study. In the papain-treated group at 6, but not at 3, months, mean pulmonary arterial blood pressure (PAPm) and pulmonary arteriolar resistance (PAR) were significantly augmented when compared with the control group. A significant correlation was found at 6 months between the Lm and ISA2 on one side, and PAPm and PAR on the other side, suggesting that the structural changes of the lung were responsible for pulmonary hemodynamic alterations.
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PMID:A six-month study of the evolution of papain-induced emphysema in the dog. 681 11

The protease hypothesis of emphysema development evolved from systems using intratracheal instillation or aerosols of heterologous enzymes, such as papain or porcine pancreatic elastase, which bear no relation to the animal species treated. Although these enzymes did produce experimental emphysema, their exogenous origin and superphysiological dosages limit their use in definitive model systems. The observation that dog leukocyte homogenates could induce canine emphysema led us to purify the causative agent from canine neutrophils. This report establishes that a single elastolytic enzyme from dog neutrophils is responsible for inducing experimental emphysema in the dog. Two purification methods were employed. The first used solvents of increasing ionic strength in a sequential extraction of acetone powders of purified dog neutrophils. The ability to initiate emphysema-like lesions was tested in every fraction of the purification and was localized in the extract with the highest true elastolytic activity. The second purification involved neutrophil intracytoplasmic organelle fractionation and established that only extracts of the lysosomal granules were capable of emphysema induction. Finally, the enzyme was purified to homogeneity from the granules using affinity chromatography and was shown to be a true elastase. Emphysema development was quantitated using mean linear intercept and was shown to be dependent on elastase concentration. There does not appear to be any other single enzyme in the canine neutrophil capable of inducing experimental emphysema.
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PMID:Emphysema induced in vitro and in vivo in dogs by a purified elastase from homologous leukocytes. 691 76


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