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Our aim was to determine whether cytokine mRNA expression is induced by experimental manipulation including artificial perfusate or ischemia-reperfusion (I/R) in an isolated, perfused rat lung model. Constant pulmonary flow [Krebs-Henseleit solution supplemented with low-endotoxin (LE) or standard (ST) bovine serum albumin 4%, 0.04 ml/g body wt] and ventilation were maintained throughout. Right and left pulmonary arteries were isolated, and the left pulmonary artery was occluded for 60 min and then reperfused for 30 min. Analysis of tumor necrosis factor-[alpha], IL-1[beta], IL-6, IL-10, and IFN-[gamma] mRNA expression by RT-PCR and evaluation of vascular permeability by bronchoalveolar lavage (BAL) fluid albumin content were conducted separately in right and left lung. Both LE and ST groups (each 12 rats) showed increases in vascular permeability by I/R (BAL fluid albumin content: 5.53 [+ or -] 1.55 vs. 15.63 [+ or -] 8.87 and 4.76 [+ or -] 2.71 vs. 16.72 [+ or -] 4.85 mg*ml BAL [fluid.sup.-1] * g lung dry [wt.sup.-1], mean [+ or -] SD; right vs. left lung in LE and ST groups, P < 0.05 between right and left). Cytokine mRNA expression was significantly higher in the I/R lung than in the control lung in the LE group, whereas it was higher in the control lung in the ST group (P < 0.05). mRNAs of not only proinflammatory but also anti-inflammatory cytokines were expressed in I/R lung, which are expected to aggravate I/R injury. The reversed pattern of cytokine mRNA expression in the ST group was possibly due to the longer perfusion of control lung with perfusate containing endotoxin, which caused no lung damage without I/R. ischemia-reperfusion injury; reverse transcriptase-polymerase chain reaction; endotoxin

Introduction: Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used for patients with septic shock, and the recommended hemoperfusion period is 2 h. However, it remains unclear whether the optimal duration is 2 h or longer. The purpose of this study was to compare the effects of PMX-DHP between conventional and longer duration of PMX-DHP. Methods: We retrospectively investigated 103 patients with sepsis who underwent PMX-DHP. The demographic data, routine biochemistry, microbiological data, and primary infection site were reviewed in the medical chart. The acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, heart rate, mean arterial pressure (MAP), vasoactive-inotropic score (VIS), and PaO2/FiO2, at baseline and day 3, were compared between the standard group (2 h of PMX-DHP) and the extended group (>2 h of PMX-DHP). Results: Median MAP was significantly lower and median VIS was significantly higher in the extended group at baseline (p < 0.05, 0.01, respectively) There were no significant differences in APACHE II score, SOFA score, and PaO2/FiO2 at baseline between the 2 groups. The increase of MAP and the decrease in VIS from baseline to day 3 were significantly greater in the extended group (p < 0.01, respectively). In the extended group, increase in PaO2/FiO2 was significantly larger in the patients who underwent ≥8 h duration than that in patients who underwent <8 h duration (p < 0.01). The ventilator-free days, the incidence of continuous renal replacement therapy, and the 28-day mortality were not different between the groups. Discussion/Conclusions: Longer duration of PMX-DHP was associated with the improved MAP and decreased volume of vasoactive-inotropic agents compared with the conventional duration. Eight and longer hours duration of PMX-DHP was associated with the improvement in the pulmonary oxygenation. Further studies are needed to confirm the efficacy of longer duration of PMX-DHP in patients with septic shock. [ABSTRACT FROM AUTHOR]

Experimental analyses of whether tumor necrosis factor (TNF)-alpha affects hemodynamic modifications and endothelium-derived vasoactive factors in anesthetized dogs reveal that TNF-alpha enhances pulmonary and systemic vascular resistance and reduces MAP transiently. Endothelin (ET)-1 factor mediates the increases in vascular resistances due to TNF-alpha, while ET-3 and NO function as vasodilators for ET-1-induced vasoconstriction. Indomethacin or L-NNA pretreatment inhibits TNF-alpha-mediated hypotension and enhances systemic vascular resistance, indicating that TNF-alpha does not function through an NO-dependent pathway.

Nishizaki and colleagues [[1]] reported in the letter to the editor that prognosis of septic neonates in earlier PMX-DHP induction was better than that in later PMX-DHP induction. Although it is theoretically possible to extend the duration of PMX-DHP treatment in neonates, it will be practically difficult to perform longer treatment in neonates because of unstable hemodynamics during PMX treatment. The criterion for excluding PMX-DHP therapy for pediatric patients with septic shock is intracranial bleeding or tendency to bleed in general. [Extracted from the article]