Respiratory mechanics in hamsters following treatment with endotracrael elastase or collagenase

Snider, Gordon L.; Sherter, Carl B.; Koo, K. W.; Karlinsky, Joel B.; Hayes, J. A.; Franzblau, Carl

doi:10.1152/jappl.1977.42.2.206

Cited by 48 publications

(15 citation statements)

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“…The present observations suggest that loss of lung elasticity is due to the decrease in elastin concentration. Lung tissue elasticity is well-correlated with elastin concentration in the growing rat (5) and elastin degradation by intratracheal or intraperitoneal administration of elastase results in a loss of lung elastic recoil (1 [8][9][10][11][12][13][14][15][16][17][18][19][20]. In our experiments, the fall in lung elastic recoil does not equal the loss in lung elastin concentration (21 and 34% of control values for recoil pressure and elastin concentration, respectively).…”

mentioning

confidence: 64%

Effects of Protein Deprivation from the Neonatal Period on Lung Collagen and Elastin in the Rat

Kalenga

Eeckhout

1989

Pediatr Res

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ABSTRACT. We have previously reported mechanical lung alterations in rats fed a protein-deficient diet from neonatal period to postnatal day 49 (12 and 8% protein versus a control 15% protein diet). From saline vol-pressure analysis, lungs from protein-deficient rats showed lower recoil pressure and needed higher pressure to rupture. In our study we have measured the collagen and elastin contents of homogenates of the lungs previously used for airfilling experiments. Results show that protein-deficient rats had lesser amounts of collagen and elastin per lung. Nevertheless tissue concentration of collagen remained constant, whereas elastin concentration was severely decreased. The decrease in lung recoil pressure is thought to be related to the lowered elastin concentration. Thus elastin accumulation, which mainly occurs between postnatal d 12 and 20, is predominantly affected by early protein deficiency with a consequent lack of increase in lung elasticity. The increased rupture pressure in protein-deficient rat lungs occurs despite the maintenance of the tissue concentration of collagen and suggests a role for other factors in this process. (Pediatr Res 26:125-127, 1989) Morphologic, biochemical, and mechanical properties of the growing rat lung are well documented (1-5). Of interest is the correlation between connective tissue accumulation, especially collagen and elastin, and changes in mechanical behavior of the lung (4). Absolute collagen content and collagen concentration increase in a linear fashion from postnatal d 4 into adulthood in proportion to lung size. The at which the saline inflated lung ruptures increases in parallel. The lung elastin concentration rises slowly from d 4 to 12, increases 3-fold between d 12 and 20, then falls to a constant level in the adult. These major changes in elastin concentration between d 12 and 20 are associated with an increase in lung elasticity measured as recoil pressure.We have previously demonstrated differences in the pattern of deflation vol pressure curves of saline filled lungs of rats fed on a protein-restricted diet either from the neonatal period or after weaning. Lungs of rats fed on a diet restricted in protein from the neonatal period had decreased recoil pressure (6), whereas protein restriction from d 28 resulted in a moderately increased recoil pressure (7). Inasmuch as we know from the observations of Myers et al. (8) rats produces an increase in lung elastin concentration, our second experiment could lend support to their conclusions. We had also observed an increase in the pressure at which the lung of protein-deficient rats ruptured. This increase could also have resulted from alterations in collagen or (and) elastin content of the lung. The major mechanical properties of lungs from rats restricted in protein from neonatal period are summarized in Table 1.The purpose of our study was to determine the amounts of collagen and elastin in lungs of rats restricted in protein from the postnatal d 8 until d 49 in our first experiment. The assays were...

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mentioning

confidence: 64%

Effects of Protein Deprivation from the Neonatal Period on Lung Collagen and Elastin in the Rat

Kalenga

Eeckhout

1989

Pediatr Res

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“…Functionally, the lungs of elastase-injected animals demonstrate changes similar to those observed in human emphysema. Lung compliance, functional residual capacity (FRC), residual volume (RV), and total lung capacity (TLC) are all increased (15)(16)(17). Hamsters with elastase-induced em- physema also develop CO2 retention (18) and right ventricular hypertrophy (19), the major clinical complications of emphysema.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we have made use of a well-characterized animal model of human emphysema, induced by intratracheal administration of elastase (15)(16)(17)(18)(19)(20), to examine directly the effect of emphysema on diaphragmatic muscle function. Studies were performed in vitro using muscle strips from the costal portion of the diaphragm.…”

mentioning

confidence: 99%

Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

Supinski¹,

Kelsen²

1982

J. Clin. Invest.

106

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A B S T R A C T The effect of emphysema on the ability of the diaphragm to generate force was examined in costal diaphragm muscle strips from 10 Golden hamsters killed 18 mo after intratracheal injection of pancreatic elastase in a dose producing hyperinflation (mean total lung capacity [TLC] = 163% of control) and generalized panacinar emphysema. 13 saline-injected normal animals served as controls. The time course of isometric tension and the effect of alterations in muscle fiber and sarcomere length on the isometric tension (T) generated in response to tetanizing electrical stimuli (length-tension [L-T] relationship) were examined. Elastase administration caused an increase in diaphragm muscle thickness and reduction in the length of costal diaphragm muscle fibers measured in situ. Emphysema significantly increased the maximum tetanic tension as a result of hypertrophy. Maximal tension corrected for increases in muscle cross-sectional area (T/cm2), however, was the same in emphysematous (E) and control (C) animals. Emphysema also shifted the muscle fiber L-T curve of the diaphragm but not of a control muscle, the soleus, toward shorter lengths. In contrast to the effects of E on the diaphragm muscle fiber L-T curve, the sarcomere L-T curve was the same in E and C. Since the length at which tension was maximal correlated closely with sarcomere number (r = 0.94; P < 0.001) reduction in the number of sarcomeres in series in muscles from emphysematous animals appeared to explain the shift in the muscle fiber L-T curve. We conclude that in elastase-induced emphysema adaptive changes both in diaphragm cross-sectional area and sarcomere number augment the force-generating ability of the diaphragm. We speculate that changes in sarcomere number compensate for alterations in muscle fiber length

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“…After rechromatography of this mixture, all of the enzyme activity and 80% of the radioactivity were found in a 780,000-dalton complex; the remainder of the radioactivity was associated with low molecular weight material. The formation of a-l-PI-elastase was studied as follows: 3H-Me-PE was a-Macroglobulin-Elastase Complexes 927 16 20 jAg Elastase/ml Plasma FIGURE 2 Comparison of the functional antielastase profile of hamster plasma with normal human plasma (PiMM) and deficient human plasma (PiZZ). Plasma samples were incubated with 3H-Me-PE and chromatographed on Sepharose 6B columns as described in Fig.…”

Section: Measurement Of Elastase-binding Molecules In Plasmamentioning

confidence: 99%

“…Investigators (2) have reported the progression of the lesion in hamsters for many months after a single instillation of elastase. Data obtained to date support the concept of long-term retention of elastase after its instillation into the lungs (3).…”

Section: Introductionmentioning

confidence: 99%

Role of alpha-macroglobulin-elastase complexes in the pathogenesis of elastase-induced emphysema in hamsters.

Stone¹,

Calore²,

Snider³

et al. 1982

J. Clin. Invest.

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A B S T R A C T Radiolabeled, enzymatically active or chloromethyl ketone-inactivated porcine pancreatic elastase was endotracheally instilled into hamsters. Gel filtration of the bronchopulmonary lavage fluid revealed two major radioactive fractions: one, eluting at 780,000 daltons, corresponding to an a-macroglobulinpancreatic elastase complex, and another, at 68,000 daltons, corresponding to an a-1-protease inhibitorpancreatic elastase complex. Elastolytic activity was recovered in the bronchopulmonary lavage fluid up to 4 d after elastase instillation and was associated with the a-macroglobulin-pancreatic elastase complex. Small amounts of this complex were recovered 15 d after instillation. When <1% (1.5-1.7 ,ug) of the usual dose of elastase was instilled into hamsters, the major radioactive complex was a-1-protease inhibitor-pancreatic elastase complex, and little or no elastolytic activity was found in the lavage fluid. In contrast to the instillation of 220 tsg of elastase, no disease or hemorrhagic reaction was detected with this low dose, and without hemorrhage only insignificant amounts of amacroglobulin-pancreatic elastase complexes were recovered from the lungs. To study the interaction of circulating antiproteases with elastase, hamster plasma was allowed to interact directly with the radiolabeled elastase; a-macroglobulin bound much more of the elastase than a-1-protease inhibitor, confirming the findings in the lung lavage experiments. The hamster's susceptibility to pancreatic elastase-induced emphysema may depend on the preferential binding of elastase to a-macroglobulin, which protects the elastolytic potential, rather than to a-1-protease inhibitor, which

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Respiratory mechanics in hamsters following treatment with endotracrael elastase or collagenase

Cited by 48 publications

References 0 publications

Effects of Protein Deprivation from the Neonatal Period on Lung Collagen and Elastin in the Rat

Effects of Protein Deprivation from the Neonatal Period on Lung Collagen and Elastin in the Rat

Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

Role of alpha-macroglobulin-elastase complexes in the pathogenesis of elastase-induced emphysema in hamsters.

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