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Abstract

Metalloproteinase (MMP)-9 plays a role in the pathogenesis of acute respiratory distress syndrome (ARDS). Polymyxin B-immobilized fiber (PMX-F) treatment improves circulatory disturbance and oxygenation in ARDS patients. We aimed to assess whether PMX-F treatment alters the blood MMP-9 and tissue inhibitor of MMP (TIMP)-1 levels in ARDS patients. Twelve ARDS patients who received PMX-F treatment and 20 healthy control volunteers were included in this study. PMX-F was carried out twice at a rate of 100 ml/min for 2 h with a time interval of 24 h. Blood MMP-9 and TIMP-1 levels were measured before and after PMX-F treatment. We monitored blood pressure and the PaO2/FiO2 (PF) ratio before and after PMX-F treatment. The mortality of ARDS patients after PMX-F treatment was 16.7%. Chest X-ray abnormalities were ameliorated in surviving patients after PMX-F treatment. Systolic and diastolic blood pressure increased significantly after PMX-F treatment (p < 0.01). The PF ratio also increased significantly after PMX-F treatment (p < 0.01). Blood MMP-9 and TIMP-1 levels in ARDS patients (126.4 +/- 36.4 and 326.5 +/- 52.5 ng/ml) were significantly higher than in controls (34.5 +/- 12.5 and 160.5 +/- 24.5 ng/ml; p < 0.01). PMX-F treatment reduced these levels significantly (the first treatment: MMP-9 85.4 +/- 28.6 ng/ml, p < 0.05, TIMP-1 265.8 +/- 36.6 ng/ml, p < 0.05; the second treatment: MMP-9 56.5 +/- 18.8 ng/ml, p < 0.01, TIMP-1 220.6 +/- 30.5 ng/ml, p < 0.01). These data suggest that MMP-9 and TIMP-1 may play a role in the pathogenesis of ARDS and that PMX-F treatment ameliorated increased MMP-9 and TIMP-1 levels in ARDS patients. Copyright 2004 S. Karger AG, Basel

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Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber.

T Tani, H. Aoki, M Kodama … (1994)

Despite the use of potent antibiotics and intensive supportive care, mortality remains high among septic shock patients, especially those with endotoxemia. To remove endotoxin directly from the blood, a material consisting of polymyxin B that is immobilized on fibers (PMX-F) and that can selectively detoxify endotoxin was developed. In a preliminary clinical study, 16 patients with septic multiple organ failure were treated with direct hemoperfusion using a PMX-F column. This therapy significantly decreased the endotoxin level from 76 pg/mL to 21 pg/mL after 2 hours of direct hemoperfusion. The hyperdynamic state of the cardiac index, which is a characteristic of endotoxic shock, returned to normal levels after treatment. In septic shock patients with a systolic pressure of less than 100 mm Hg, the systolic arterial pressure increased significantly from the pretreatment level. The alleviation of fever caused by this therapy continued until the day after treatment. Of the 16 patients who underwent this therapy, 9 were alive 2 weeks after this therapy and 7 patients were discharged from the hospital alive. Hemoperfusion with PMX may be an effective treatment for sepsis and septic shock.

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Direct hemoperfusion using a polymyxin B immobilized column improves acute respiratory distress syndrome.

Keisaku Fujimoto, Kenji Tsushima, K Hora … (2001)

Acute respiratory distress syndrome (ARDS) is characterized by a high mortality rate. We have studied whether direct hemoperfusion using a polymyxin B immobilized fiber column (PMX-DHP) is effective for acute lung injury (ALI) and ARDS. Two ALI and eighteen ARDS patients were evaluated, four congestive heart failure (CHF) patients were evaluated as cardiogenic pulmonary edema, and we retrospectively compared the outcome with ten patients with ARDS who had been hospitalized between 1990 and 1998 as the untreated group. PMX-DHP was carried out twice at a rate of 80-100 ml/minute for 2 hours, with a time interval of approximately 24 hours. We monitored systolic blood pressure (BP), diastolic BP, and the PaO(2)/FIO(2) (PF) ratio before and after PMX-DHP treatment. The mortality was classified if patients were alive at day 30 after initiating PMX-DHP. The mortality of ARDS patients was approximately 20%. Systolic BP increased significantly from 106 +/- 20 to 135 +/- 21 and to 125 +/- 20 mmHg on the following day. Diastolic BP increased from 61 +/- 16 to 78 +/- 15, and to 72 +/- 12 mmHg. The PF ratio increased significantly from 125 +/- 54 to 153 +/- 73, and 163 +/- 78 Torr. CHF patients did not reveal improvement of systolic, diastolic BP, and PF ratio after PMX-DHP. Eight of ten patients in the untreated group died through exacerbated ARDS. In ARDS patients, PMX-DHP improved circulatory disturbance and oxygenation despite the underlying diseases. The mortality improved compared with that before induction of PMX-DHP. Copyright 2002 Wiley-Liss, Inc.

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Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment.

Takeshi Nakamura, I Ebihara, N. Shimada … (1998)

The authors measured plasma metalloproteinase (MMP)-9 and corresponding monocyte mRNA in 20 patients with septic shock. Plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels were significantly higher in the 10 nonsurviving patients with septic shock than in 10 surviving patients and 25 normal controls. Hemoperfusion using polymyxin B immobilized on fibers (PMX-F), a reportedly effective treatment for septic shock, was studied for effects on MMP-9 in the patients. Increases in plasma MMP-9 concentrations and corresponding monocyte mRNA levels were attenuated significantly by PMX-F treatment in both nonsurviving and surviving patients. These data suggest that plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels may be useful prognostic markers in septic shock, and that PMX-F treatment affects MMP-9.

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PubMed ID:: 15148453

DOI:: 10.1159/000078494

ScienceOpen disciplines: Chemistry

Keywords: Aged,Blood Pressure,drug effects,Endotoxins,blood,Female,Hemoperfusion,methods,Humans,Male,Matrix Metalloproteinase 9,Middle Aged,Polymyxin B,pharmacology,therapeutic use,Respiratory Distress Syndrome, Adult,mortality,therapy,Respiratory Function Tests,Tissue Inhibitor of Metalloproteinase-1,Treatment Outcome

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Effect of polymyxin B-immobilized fiber on blood metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in acute respiratory distress syndrome patients.

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Karger: Nephrology

Most cited references 12

Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber.

Direct hemoperfusion using a polymyxin B immobilized column improves acute respiratory distress syndrome.

Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment.

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