BackgroundWe previously reported that measuring circulating serum mRNAs using quantitative one-step real-time RT-PCR was clinically useful for detecting malignancies and determining prognosis. The aim of our study was to find crucial serum mRNA biomarkers in esophageal cancer that would provide prognostic information for post-esophagectomy patients in the critical care setting.MethodsWe measured serum mRNA levels of 11 inflammatory-related genes in 27 post-esophagectomy patients admitted to the intensive care unit (ICU). We tracked these levels chronologically, perioperatively and postoperatively, until the two-week mark, investigating their clinical and prognostic significance as compared with clinical parameters. Furthermore, we investigated whether gene expression can accurately predict clinical outcome and prognosis.ResultsCirculating mRNAs in postoperative esophagectomy patients had gene-specific expression profiles that varied with the clinical phase of their treatment. Multivariate regression analysis showed that upregulation of IL-6, VWF and TGF-β1 mRNA in the intraoperative phase (p = 0.016, 0.0021 and 0.009) and NAMPT and MUC1 mRNA on postoperative day 3 (p < 0.01) were independent factors of mortality in the first year of follow-up. Duration of ventilator dependence (DVD) and ICU stay were independent factors of poor prognosis (p < 0.05). Therapeutic use of Sivelestat (Elaspol®, Ono Pharmaceutical Co., Ltd.) significantly correlated with MUC1 and NAMPT mRNA expression (p = 0.048 and 0.045). IL-6 mRNA correlated with hypercytokinemia and recovery from hypercytokinemia (sensitivity 80.9%) and was a significant biomarker in predicting the onset of severe inflammatory diseases.ConclusionChronological tracking of postoperative mRNA levels of inflammatory-related genes in esophageal cancer patients may facilitate early institution of pharamacologic therapy, prediction of treatment response, and prognostication during ICU management in the perioperative period.

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Background Breathing during a marathon is often empirically conducted in a so-called "2:2 breathing rhythm," which is based on a four-phase cycle, consisting of the 1st and 2nd inspiratory and the 1st and 2nd expiratory phases. We developed a prototype ventilator that can perform intermittent positive pressure ventilation, mimicking the breathing cycle of the 2:2 breathing rhythm. This mode of ventilation was named the marathoners' breathing rhythm ventilation (MBV). We hypothesized that MBV may have a lung protective effect. Methods We examined the effects of the MBV on the pulmonary pre-edema model in isolated perfused rabbit lungs. The pulmonary pre-edema state was induced using bloodless perfusate with low colloid osmotic pressure. The 14 isolated rabbit lung preparations were randomly divided into the conventional mechanical ventilation (CMV) group and MBV group, (both had an inspiratory/expiratory ratio of 1/1). In the CMV group, seven rabbit lungs were ventilated using the Harvard Ventilator 683 with a tidal volume (TV) of 8 mL/kg, a respiratory rate (RR) of 30 cycles/min, and a positive end-expiratory pressure (PEEP) of 2 cmH 2 O for 60 min. In the MBV group, seven rabbit lungs were ventilated using the prototype ventilator with a TV of 6 mL/kg, an RR of 30 cycles/min, and a PEEP of 4 cmH 2 O (first step) and 2 cmH 2 O (second step) for 60 min. The time allocation of the MBV for one cycle was 0.3 s for each of the 1st and 2nd inspiratory and expiratory phases with 0.2 s of intermittent resting between each phase. Results Peak airway pressure and lung wet-to-dry ratio after 60 min of ventilation were lower in the MBV group than in the CMV group. Conclusion MBV was considered to have a lungprotective effect compared to CMV.

Purpose: The role of volatile anaesthetics on nitric oxide (NO)-dependent relaxation is unclear in the pulmonary circulation. We examined the effects of isoflurane on NO-dependent relaxation in isolated perfused rabbit lungs. Methods: Eighteen rabbit lungs were pedused in a constant-flow recirculation manner. In study I ( n = 12), acetylcholine (ACh, 4 x l0 '~ ~ M) or nitroglycerine (NTG, 6 x 10"1~ -8 M) was cumulatively injected into the pulmonary artery in the absence or presence of isoflurane (I, 2 MAC). In study 2 (n=6), ACh was injected as in study I in the presence or absence of No-nitro-L-arginine methyl ester (L-NAME, 100pM), an NO synthesis blocker. In all experiments, indomethacin was administered to prevent formation of vasoactive prostanoid metabolites, and the pulmonary vessels were preconstricted with prostaglandin F2~ (PGF2~) infused before ACh or NTG injection. The ACh-or NTG-induced relaxation was expressed as % decrease in PGF2~ preconstriction. Results: Isoflurane at 2 MAC attenuated the dose-dependent relaxation to ACh at doses of 4 x 1 9 9 M and 4 x I 0 -~ M from 27.8 • 4.3% and 38.8 • 5.3% to 17.0 _ 3.5% and 25.5 • 4.9%, respectively (P < 0.05). Isoflurane did not change the dose-dependent relaxation to NTG and L-NAME abolished the ACh-induced relaxation. Conclusion: Isoflurane inhibited NO-dependent relaxation in the pulmonary circulation at a site distal to the endothelial cell receptor-mediated responses but proximal to guanylate cyclase activation of vascular smooth muscle. Acetylcholine-induced relaxation in isolated pedused rabbit lungs was regulated primarily by NO.Objectif : Nous connaissons mal I'influence des anesth~siques volatils sur la relaxation de la circulation pulmonaire d~pendante du monoxyde d'azote (NO). Cette ~tude analyse les effets de I'isoflurane sur la relaxation NO-d~pendante de poumons perfus~s de lapins. M~thodes : Dix-huit poumons de lapins ont ~t~ perfus~s par recirculation ~ d~bit constant. Dans I'~tude I (n= 12), on a inject~ de rac~tylcholine (ACh, 4 x 10 -I-10 8 M) ou de la nitroglycerine (NTG, 6 x 10 l0 10-8 M) avec ou sans isoflurane (I ,2 MAC). Dans I'~tude 2, (n--6), I'ACh a ~t~ inject~e seule comme dans I'~tude I ou associ~e au No-nitro-L-arginine m~thyl ester (L-NAME, 100 HM), un inhibiteur de la synth~se du NO. Toutes les experiences ont comport~ I'administration d'indom~thacine pour pr~venir la formation de m~tabolites protanoldes vasoactifs ainsi que la constriction pr~alable avec de la prostaglandine F2~ (PGF2~) administr~e en perfusion avant I'injection de I'ACh et de la NTG. La relaxation induite par ACh ou NTG ~tait exprim~e en fonction de la diminution du pourcentage de constriction provoqu~e par la PGF2~. l~.sultats : Eisoflurane ~ 2 MAC att~nuait la relaxation ~ I'ACh proportionnellement aux doses de 4 x 10 9 et 4 x 10 8 M respectivement de 27,8 • 4,3% et 38,8 • 5,3% ~ 17,0 _ 3,5% et 25,5 • 4,9% (P < 0,05). l'isoflurane ne modifiait la relaxation de la circulation pulmonaire NO-d~pendante ~ la NTG ; le L-Name abolissalt la relaxation induit...