Plasma Levels Of Granulocyte Elastase Research Articles

Granulocyte elastase release and pulmonary hemodynamics in patients with mitral valvular disease.

In patients with atrial septal defect in whom pulmonary hypertension could develop as a consequence of left-to-right shunt, the extent of neutrophil-mediated lung injury induced by cardiopulmonary bypass (CPB) is related to the degree of increase in the preoperative pulmonary artery pressure. In the present study, we investigated the relationship between levels of granulocyte elastase (GEL) after CPB and preoperative pulmonary hemodynamics or changes in pulmonary function after the operation in patients with mitral valve disease, in whom pulmonary hypertension could develop as a result of pulmonary venous congestion. The plasma levels of GEL were measured before and after CPB in patients who underwent mitral valve replacement. Respiratory index (RI) was evaluated preoperatively and postoperatively. Preoperative pulmonary hemodynamics were determined within one month of the operation. Granulocyte elastase level rose significantly after CPB from baseline (134.3 +/- 44.6 mg/L versus 2042.1 +/- 1215.0 mg/L; p <0.001). Peak level of GEL was significantly correlated with preoperative systolic pulmonary artery pressure (r = 0.71; p = 0.020), mean pulmonary artery pressure (r = 0.64; p = 0.046), pulmonary capillary wedge pressure (r = 0.68; p = 0.032), and pulmonary-to-systemic arterial pressure ratio (r = 0.64; p = 0.045), but not with the hemodynamic variables for pulmonary blood flow or pulmonary resistance. Moreover, the value of (Postoperative RI - Preoperative RI)/Preoperative RI was positively correlated with the peak level of GEL (r = 0.76; p = 0.011). In conclusion, in patients with mitral valvular disease, as in those with atrial septal defect, the increase in GEL level after CPB is proportional to the increase in preoperative pulmonary artery pressure, which may cause the accordant pulmonary vascular damage.

Oxidant-Antioxidant Balance in Granulocytes During ARDS: Effect of N-Acetylcysteine

The production of cytotoxic oxygen radicals by activated granulocytes is a proposed mechanism of lung injury in ARDS. Protective effects of N-acetylcysteine (NAC) have been described in experimental and clinical ARDS. NAC could act in part by replenishing the intracellular stores of glutathione (GSH) in activated granulocytes, leading to detoxification of oxygen radicals produced by these cells. To test this hypothesis, 16 patients in the early phase of ARDS were randomized to receive either NAC (n=8) or placebo (n=8); granulocyte GSH, granulocyte oxygen radical production, and plasma levels of granulocyte elastase were measured in blood samples drawn sequentially within 8 h after the onset of ARDS (day 0), and then 24 (day 1), 72 (day 3), and 120 h (day 5) after the first sample; treatment with NAC or placebo was started immediately after day 0 and stopped just after day 3. Granulocyte GSH was significantly higher on days 1 and 3 when NAC was received by the patient. Unstimulated oxygen radical production, as measured <i>ex vivo</i> by luminol- and lucigenin-amplified chemiluminescence (CL), was higher in granulocytes from ARDS patients than from healthy control subjects, but was not influenced by NAC. The plasma levels of granulocyte elastase were five to eight times above the upper normal limit on day 0, decreased steadily until day 5, and were uninfluenced by NAC. In summary, parenteral NAC treatment started within 8 h of diagnosis increases the intracellular GSH in the granulocytes of ARDS patients without decreasing spontaneous oxidant production by these cells. The mechanisms of the protective effects of this drug previously reported in experimental and clinical ARDS remain to be established.

The effects of urinastatin on the plasma levels of granulocyte elastase during open heart surgery under simple deep hypothermia.

Changes in granulocyte elastase (GLE) and Beta-gluculonidase (Beta-gl) were observed during open heart surgeries which were performed under deep hypothermia with surface cooling. In addition, the effect of urinary trypsin inhibitor, urinastatin, on the activities of these enzymes was studied. The patients were divided into three groups, namely group U-I with intravenous injection of 6000 u.kg(-1) of urinastatin before cooling, group U-II administered with an additional 6000 u.kg(-1) after warming to 30 degrees C, and an untreated group (Group C). The plasma level of GLE increased significantly in the three groups compared with the level before cooling respectively. In the group U-II, the GLE level after the warming was lower than that in the control group. The serum level of Beta-gl increased significantly in the three groups at the end of rewarming (36 degrees C). The release of GLE from lysosomes in granulocytes was inhibited in the group U-II. The insufficient inhibition of GLE release in the group U-I is probably due to relatively short half-life of urinastatin. Therefore double administration of 6000 u.kg(-1), before and after the cooling, may be required to achieve the therapeutic effect. Consequently, urinastatin appears to be useful in open heart surgery under deep hypothermia with surface cooling.

Influence of Haemodialysis Membranes on the Release of Granulocyte Elastase

The advantages of multiparameter assessment in the evaluation of the blood compatibility of biomaterials underline the importance of investigating possible relevant parameters. In this respect, a study has been made of granulocyte elastase to establish the influence of haemodialysis membranes on the release of this serine proteinase. Plasma levels of granulocyte elastase were determined as a complex with its natural inhibiter, alpha 1-proteinase. This elastase - alpha 1 proteinase (E- alpha 1 Pi) inhibitor complex was measured by a highly sensitive enzyme-linked immunoassay. The membranes evaluated were Cuprophan (15-11, Travenol) and polysulphone (F40, Fresenius). Samples were taken from patients undergoing maintenance haemodialysis, before the start of dialysis, after 15 and 90 minutes and again at the end of dialysis (4 h). This investigation clearly demonstrates the different response of the dialysers, and on correcting for surface area, the end-dialysis level of E-alpha 1 Pi remained significantly greater for the Cuprophan membrane. The results support the view that the release of granulocyte elastase is a relevant parameter for inclusion in membrane compatibility assessment.

Perioperative fluctuation in plasma levels of granulocyte elastase and alpha-1-antitrypsin: The influence of the severity of surgical intervention and their effect on the respiratory index

In order to examine whether granulocyte elastase is related to surgical stress and postoperative respiratory function, the perioperative plasma levels of granulocyte elastase and alpha 1-antitrypsin were periodically measured in 49 patients who underwent various operations and the correlation between these levels and the respiratory index was examined. A strong correlation between elevated plasma levels of granulocyte elastase and the degree of aggressiveness of surgery was quite conspicuous; as the operative intervention became more severe, the plasma levels of granulocyte elastase were higher. The plasma level of alpha 1-antitrypsin was in inverted relation to granulocyte elastase. Moreover, marked and prolonged elevation of plasma granulocyte elastase levels induced postoperative pulmonary complications. A highly significant positive correlation was found between the plasma level of granulocyte elastase and the respiratory index. Elevated granulocyte elastase and/or decreased alpha 1-antitrypsin may therefore be implicated in the etiology of postoperative respiratory dysfunction. Thus, an abnormal elevation of plasma granulocyte elastase may allude the existence of postoperative respiratory dysfunction.

Beta-2-microglobulin and main granulocyte components in hemodialysis patients.

Plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1-PI) increased during hemodialysis from 110 +/- 10 to 506 +/- 66 micrograms/L using dialyzers made of polyamide, from 95 +/- 2.2 to 211 +/- 54 micrograms/ml with hemophane and from 114 +/- 10 to 203 +/- 25 using dialyzers made of polysulfone. Plasma lactoferrin values were also significantly higher during hemodialysis with polyamide (772 +/- 110 micrograms/L) compared with hemophane (268 +/- 2.2) and the polysulfone (278 +/- 31 micrograms/L) dialyzer. After dialysis each dialyzer was rinsed. We found the lowest concentration of lactoferrin (902 +/- 254 micrograms/L) and E-alpha 1-PI (739 +/- 162 micrograms/L) after rinsing polysulfone dialyzers, whereas the highest concentrations were observed after rinsing the polyamide dialyzer (lactoferrin: 2,426 +/- 314; E-alpha 1-PI: 1,134 +/- 144 micrograms/L). Hemodialysis with polysulfone dialyzers caused significantly lower plasma levels of beta-2-microglobulin compared with polyamide or hemophane membranes despite significantly lower levels in the rinsing solutions. Our data indicate that low plasma levels of main granulocyte component observed with polysulfone and hemophane dialyzers are not the result of higher membrane adsorption of E-alpha 1-PI and lactoferrin. These main granulocyte components are not related to beta-2-microglobulin levels of both plasma and rinsing solutions.

TIME COURSE OF GRANULOCYTE ELASTASE IN SURGICAL CASES WITH RESPIRATORY DYSFUNCTION

To investigate the role of degeneration or destruction of white blood cells (WBC) in 5 patients with respiratory dysfunction who underwent surgical operation, we measured the plasma levels of granulocyte elastase (GEL), α1-antitrypsin (α1-AT), WBC and respiratory index. At the same time or after the decrease in WBC, the GEL level was increased and respiratory dysfunction appeared. After operation, the α1-AT level was decreased in 3 out of 5 cases.It was thought that GEL discharged from WBC may produce endothelial cell damage in the lung. GEL in the lung may be activated as a result of decreased αl-AT after operation. Neutropenia, decreased αl-AT and increased GEL level may play an important role in the etiology of ARDS.

Plasma Proteinases, Proteinase Inhibitors and Other Selective Plasma Proteins following Aortofemoral Bypass Operation

Monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins was evaluated in patients undergoing Y-graft aortofemoral bypass operation. Fast-reacting acute-phase proteins (C-reactive protein, antichymotrypsin, alpha 1-acid glycoprotein) and slow-reacting proteins (haptoglobin, alpha 1-antitrypsin) increased significantly 48-120 h after operation. By contrast, no significant increase was found between plasma ceruloplasmin levels before clamping and after declamping. Activity and concentration of alpha 2-macroglobulin decreased postoperatively and remained significantly lowered throughout the observation period. Plasma levels of granulocyte elastase were elevated significantly 1 h after declamping, whereas trypsin-binding capacity decreased immediately after the release of the clamp. Aprotinin pretreatment caused higher trypsin-binding capacity of the plasma, significantly lower 'unspecific' proteolytic (azocasein-hydrolyzing) activity and significantly lower non-TCA precipitable low molecular weight plasma protein concentration. Our results confirm the data of several authors that monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins may be helpful in evaluating surgical patients postoperatively.

Plasma levels of granulocyte elastase during hemodialysis: Effects of different dialyzer membranes

Plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor during hemodialysis were investigated in 15 patients (37.4 +/- 3.2 years) undergoing maintenance hemodialysis (47.0 +/- 12.9 months) with dialyzers made from cellulose hydrate, cuprophan, polymethylmethacrylate, ethylene-vinyl alcohol copolymer, and polyacrylonitrile. Cellulose hydrate membrane caused a maximal increase of the plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI: 1,659.0 +/- 256.8 ng/ml). Patients dialyzed with polyacrylonitrile dialyzers failed to exhibit comparable plasma levels of granulocyte elastase (E-alpha 1PI: 237.8 +/- 22.9 ng/ml). During hemodialysis plasma E-alpha 1PI values rose to a peak 643.0 +/- 174.7 ng/ml in patients on polymethylmethacrylate dialyzers, to 557.5 +/- 120.0 ng/ml on cuprophan dialyzers, but to only 381.9 +/- 54.0 ng/ml on ethylene-vinyl alcohol copolymer dialyzers. Plasma lysozyme levels decreased significantly in the presence of polyacrylonitrile and polymethylmethacrylate membranes. We conclude that the degree of PMNs stimulation depends on the nature of the dialyzer membrane material. The following membranes induce a reaction of increasing intensity: polyacrylonitrile, ethylene-vinyl alcohol copolymer, cuprophan, polymethylmethacrylate, and cellulose hydrate.

Effect of Different Dialyzers on Proteinases and Proteinase Inhibitors during Hemodialysis

The effect of different membrane materials on plasma levels of granulocyte elastase, 'unspecific' proteolytic (azocasein-hydrolyzing) activity, and activity and concentration of the main plasma proteinase inhibitors alpha 1-proteinase inhibitor (alpha 1PI) and alpha 2-macroglobulin during hemodialysis was investigated. Cuprophan (679.6 +/- 80.0 ng/ml) and polymethyl methacrylate (873.0 +/- 20.6 ng/ml) membranes caused a significantly higher maximal increase of plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor (E-alpha 1PI) complex compared with polyacrylonitrile (395.3 +/- 56.0 ng/ml) or polysulfone (295.2 +/- 41.3 ng/ml) membranes (healthy subject 70.3 +/- 4.4 ng/ml). The activity of alpha 1PI increased significantly during hemodialysis using polyacrylonitrile (+36%) or polysulfone (+29%) membranes, whereas this increase was less using cuprophan (+6%) or polymethyl methacrylate (+8%) membranes. The reverse effect, however, was observed analyzing alpha 1PI concentrations (cuprophan +33%, polymethyl methacrylate +23%, polyacrylonitrile +12%, polysulfone +7%). 'Unspecific' proteolytic activity and non-trichloroacetic acid-precipitable small molecular weight plasma protein fraction decreased significantly during hemodialysis in the presence of all four membranes. We conclude that neutral granulocyte proteinases can be released during hemodialysis independent of the change of white blood cells during the 1st h of dialysis therapy.