Angiopoietin Balance in Septic Shock Patients Treated by Direct Hemoperfusion With Polymyxin B‐immobilized Fiber

Abstract

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. We previously reported elevated levels of vascular endothelial growth factor and its receptor (fms-like tyrosine kinase-1) in patients with septic shock, then investigated two kinds of angiopoietins in those patients. An enzyme-linked immunoassay was used to measure serum angiopoietin-1 and -2 levels in 12 patients with septic shock who were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The angiopoietin-1 level was lower in patients with septic shock (7.01 +/- 10.08 ng/mL) than in controls (28.24 +/- 11.61 ng/mL, P < 0.001), but the angiopoietin-2 level was higher in septic shock patients (40.83 +/- 30.13 ng/mL vs. 2.47 +/- 1.78 ng/mL, P < 0.001). Between seven survivors and five non-survivors there was no significant difference in angiopoietin-1 levels before DHP-PMX therapy. During DHP-PMX therapy, however, the angiopoietin-2 level was significantly decreased in survivors (31.52 +/- 26.15 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.035). Moreover, at the end of the therapy, the angiopoietin-1 level was significantly lower in non-survivors (1.14 +/- 1.30 ng/mL vs. 10.43 +/- 13.56 ng/mL, P = 0.042), but the angiopoietin-2 level in non-survivors was significantly higher (70.79 +/- 40.47 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.019). The angiopoietin-2 level may be associated with vascular permeability in septic patients, and angiopoietins may be suitable markers of disease severity and mortality.

Treatment of acute exacerbation of idiopathic pulmonary fibrosis with direct hemoperfusion using a polymyxin B-immobilized fiber column improves survival

“…The present study also found significantly decreased white blood cell and neutrophil counts in patients treated with PMX-DHP than in patients treated without PMX-DHP. Treatment of AE-IPF or septic shock with PMX-DHP has also been reported to decrease the concentrations of serum matrix metalloproteinase (MMP)-9 [26], vascular endothelial growth factor (VEGF) [27], and angiopoietin-2 [28,29], which can facilitate vascular permeability. Direct interactions between activated neutrophils and endothelial cells can induce production of angiopoietin-2 by endothelial cells [30].…”

Serum TNF‐Related and Weak Inducer of Apoptosis Levels in Septic Shock Patients

“…Inter‐ and intra‐assay variations were less than 10%. In the analysis for angiopoietins, the serum samples were measured by enzyme‐linked immunoassay (R & D Systems) in duplicate, as previously described (4,5).…”

“…In septic patients treated with DHP‐PMX, we have previously investigated plasma levels of vascular endothelial growth factor (VEGF) and angiopoietins, finding no differences in VEGF levels between septic shock patients and controls (4). In contrast, angiopoietin‐1 levels were found to be lower and angiopoietin‐2 levels to be higher in septic shock patients than in controls (5). Quiescent endothelial cells are attached to pericytes that constitutively produce angiopoietin‐1, which reacts with the endothelial tyrosine kinase receptor Tie2 as a vascular maintenance factor (6).…”

Angiopoietin Balance in Septic Shock Patients With Acute Kidney Injury: Effects of Direct Hemoperfusion With Polymyxin B‐Immobilized Fiber

“…We demonstrated that a dysregulated angiopoietin balance was associated with the mean blood pressure and PaO 2 /FiO 2 (PF) ratio in sepsis patients treated with a polymyxin B‐immobilized fiber column (DHP‐PMX) . This result suggests that a dysregulated angiopoietin balance may play a role in the pathogenesis of vascular permeability, and that DHP‐PMX therapy ameliorates the angiopoietin balance in patients with sepsis.…”