OUAR DIARY

IARS 2015 Annual Meeting 発表報告

3月21—24日にハワイ・ホノルルで行われましたIARS 2015で当教室から9名の先生が発表致しました。当教室では海外の学会に参加するだけではなく、積極的に研究成果を発表しております。
以下に簡単ですが、発表要旨、質疑応答の内容を報告します。

M.Kinoshita

GLUTAMATE TRANSPORTER-1 IPLAYS AN IMPORTANT ROLE IN THE DEVELOPMENT OF MIRROR IMAGE PAIN IN THE SPARED NERVE INJURY MODEL IN RATS

We studied the pathogenesis of Mirror Image Pain (MIP) using Spared Nerve Injury (SNI) model rats. The incidence of MIP in SNI rats was 33.3%. We measured expression of mRNAs in L5 spinal cord to investigate the pathogenesis of MIP. Then, only glutamate transporter-1 (GLT-1) was suppressed bilaterally in SNI rats compared with naive rats. Therefore, we focused on GLT-1. We further compared GLT-1 in the rats with and without MIP. However, Expression of GLT-1 didn’t change significantly. Bilateral GLT-1 down regulation might play a role in the development of MIP, although further studies will be required.

Questions & Answers

Q1Would you plan to try the genetic methods or the other way?
A1I would like to try gene transfer of GLT-1 into the spinal cord, or drug intervention.
Q2What do you think this result that the incidence of MIP did not change significantly?
A2I guess that the other glutamate transporters or glutamine synthases may affect the change of GLT-1.
Q3Did you study expression of mRNAs in the spinal cord only? Do you have a plan to study the brain?
A3We guess that the primary cause of MIP exist in the spinal cord. Because there is no report studying the brain about MIP, however there are some reports studying the spinal cord. Then, we focused on the spinal cord.
Q4Was the incidence of MIP in SNI rats too high?
A4Li et al. reported that the incidence of MIP in the SNI rats was 25%. Therefore, we consider that the result in this study (the incidence of MIP was 33%.) is appropriate.

N.Tanioka

THE ROLE OF TRANSCRIPTION FACTOR BACH1 IN A RAT MODEL OF ACUTE LIVER INJURY INDUCED BY EXPERIMENTAL ENDOTOXEMIA

In a septic liver injury model, cytoprotective HO-1 is thought to be induced by oxidative stress and free heme released from hepatic heme proteins. A heme-responsive transcription factor Bach1 is a key regulator of the HO-1 expression. In this study, HO-1 gene expression was upregulated and ALAS1 gene expression was downregulated after LPS treatment. Bach1 gene expression was also upregulated, on the other hand, nuclear Bach1 protein showed transient decline just after LPS treatment. These findings suggest that free heme is involved in hepatic injury and Bach1 is exported from nucleus by binding with heme, allowing transcriptional activation of the HO-1 gene.

Questions & Answers

Q1Have you ever tried to measure the concentration of free heme?
A1An accurate measurement of the concentration of free heme by conventional methods is very difficult. We are trying a novel method now.
Q2Which do you think is the key player in septic tissue injury, heme or hemin?
A2I think hemin (free heme) must be the key player.

K.Kuroda

Plasma levels of Histidine-Rich Glycoprotein in Critically Ill Patients

Histidine-Rich Glycoprotein (HRG) is a protein produced in liver. In this study, we measured HRG levels and assessed the relations between HRG levels and other parameters in SIRS patients. We demonstrated that the HRG levels in SIRS patients were significantly low, and that the HRG levels in septic patients were still lower than those in non-septic SIRS patients. These results suggested that the lower HRG levels might indicate the higher severities of patients, and that HRG could be a useful marker for the severity.

Questions & Answers

Q1This is the study of new marker for sepsis. Results are clear and very interesting. Especially comparing septic patients and non-septic patients, there were significant differences. You should collect more cases, maybe twice or more.
A1Yes, we should go on.
Q2Do you have data in time course or only one time?
A2In this study, we only check one time.
We have some data about time course. In patients with non-survivor, HRG levels tended to keep lower level.
Q3Do the data change 24 hours later?
A3I’m not sure, but maybe Yes. We should check it.

Y.Hikasa

Bilateral Bronchial dehiscence with pneumonia after lung transplantation successfully managed with veno-venous extracorporeal membrane oxygenation under spontaneous breathing

Bronchial dehiscence is a very rare but disastrous complication after lung transplantation (LTx). We experienced a case of bilateral dehiscence with pneumonia after LTx. In this case, it was impossible to prevent hypoxia and hypercapnia due to not only bronchial fistulas but also pneumonia with low positive pressure ventilation. VV-ECMO under spontaneous breathing offered bronchial rest and oxygenation until fistulas and pneumonia had healed. Bilateral bronchial dehiscence after LTx was successfully managed by VV-ECMO without any complication.

Questions & Answers

Q1Which vessel were selected as cannulation site for ECMO ?
A1Femoral vein
Q2How did you do for respiratory management during ECMO ?
Could you manage the patient with pneumothorax under mechanical ventilation ?
A2We used High Flow Oxygenation under spontaneous breathing to prevent positive airway ventilation.
Q3Could you maintain ECMO at low ACT value?
Are there any evidences that support low ACT during ECMO?
A3Generally, ACT should be controlled 180-200 in ECMO guideline.
But we controlled ACT value from 130-150 with heparin-coated cannulas to prevent bleeding from anastomosis. Although we did not have any evidence about this value, we selected this value to prevent complication, especially, bleeding.

M.Yamaoka

DYNAMIC CHANGE IN BACH1 EXPRESSION IN A RAT MODEL OF GLYCEROL-INDUCED ACUTE KIDNEY INJURY

In the present study, using a rat model of glycerol-induced AKI, we examined changes in the gene expression of Bach1, HO-1 and ALAS1 and protein expression of HO-1 and nuclear Bach1. Glycerol treatment caused rhabdomyolysis-induced AKI. Renal HO-1 mRNA expression and protein levels increased and renal ALAS1 mRNA expression decreased. Nuclear Bach1 protein levels significantly decreased 2−3 h after the treatment, followed by Bach1 mRNA increase. These results indicate the increase in intracellular free heme concentration and nuclear export of Bach1 protein and compensatory increase in Bach1 mRNA.

Questions & Answers

Q1Explain about the relationship between dynamic change of nuclear Bach1 protein and that of renal Bach1 mRNA.
A1Different from HO-1, following to decrease in nuclear Bach1 protein, Bach1 mRNA gradually increased. We think these results indicate the Bach1 export from nuclear due to increase in intracellular free heme and compensatory activation in Bach1 mRNA to restore intracellular homeostasis.
Q2Have you ever used Bach1 knockout mice, or are you planning to challenge it?
A2I have never experienced it. For now, I don’t have any plan. I’m sure it would be great if I have a chance to challenge an experiment using Bach1 knockout mice.

K.Arakawa

ULTRASOUND-ASSISTED PERCUTANEOUS NUCLEOTOMY IN PATIENT WITH CERVICAL HERNIATED DISC: A CASE REPORT

In general, Percutaneous Nucleotomy (PN) has been performed under fluoroscopy and/or CT guidance. On the other hand, recently ultrasound (US) -guided block especially in the cervical region may improve patient safety. In the case, we report an US-assisted percutaneous cervical nucleotomy and some advantages of this procedure. Firstly, using US improves patient safety to avoid the important structures and to decide the safety needle path. One of the reasons is that the position during the procedure may be different from the position while MRI/CT is taken. Secondly, US is also useful to decrease radiation exposure for patient and health care provider.

Questions & Answers

Q1Actually, how did you use US and fluoroscopy for the patient?
A1US for a puncture, fluoroscopy for confirmation of the needle position.
Q2Can you perform it from back side?
A2I guess it is difficult. Because there are some artery, many nerve route and spinal cord.

T.Kanazawa

PREOPERATIVE BRAIN NATRIURETIC PEPTIDE IN PEDIATRIC CARDIAC SURGERY PATIENTS: ITS ASSOCIATION WITH POSTOPERATIVE OUTCOMES

The relationship between BNP and postoperative acute prognosis in pediatric cardiac patients has not evaluated well. We conducted a prospective observational study to investigate the relationship between perioperative BNP and postoperative serious adverse events.
71 children under 15y.o who underwent pediatric cardiac surgery were enrolled during study period from 2012-2014. BNP was measured at 3 points (preoperatively, POD1 and POD3). The definition of SAE was 1)Death in the ICU, 2)ECMO, 3)cardiac arrest, 4)re-operation for hemodynamic instability. We compared patients background between SAE(+) group and SAE(-) group. BNPpre of SAE(+) group was statistically higher than that of SAE(-) group. (p=0.01). We calculated cutoff BNP 1000pg/ml from ROC analysis. We performed multivariate analysis to investigate independent association between BNPpre >1000pg/ml and SAE. Only BNPpre >1000pg/ml was related to the incidence of SAE (Odds Ratio 20, p=0.008). BNPpre was independently associated with the incidence of SAE. BNPpre will be a good predictor of the incidence of SAE.

Questions & Answers

Q1Have you changed patient management after this study?
A1We have not changed our practice now, however we are processing prospective study to investigate the utility of BNP guide therapy.
Q2How many single ventricle patients were included?
A2We included more than 20 single ventricle patients.
Q3How do you explain the patient who had SAE with BNPpre less than 1000pg/ml?
A3That is the limitation. The sensitivity and specificity were 63% and 92%.
Q4Can you explain the relationship about RACHS-1?
A4RACHS-1 is the severity of the operation. RACHS-1 was not related with SAEs after multivariate analysis. BNPpre is stronger predictor for SAEs.
Q5How was patient’s ASA PS?
A5We excluded ASAⅠand Ⅱ patients. All patients ASA PS were more than Ⅲ.

S.Okahara

THE USE OF NEURALLY ADJUSTED VENTILATORY ASSIST IN SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME WITH INFLUENZA PNEUMONIA UNDERGOING EXTRACORPOREAL MEMBRANE OXYGENATION

We reported new advanced function of NAVA as an objective indicator of breathing effort. This case is a 40-year-old man suffering severe ARDS secondary to influenza (H1N1) pneumonia, and for the patient ECMO was established immediately. First weaning trial failed because we overestimated the recovery of native lung. At second weaning trial, we used Edi monitoring to assess his breathing effort and the timing of weaning. Edi reflected the breathing effort and told us the information for ECMO weaning. The advantage of NAVA and Edi monitoring is not only synchronized proportional assist but also assessment of ventilatory support during spontaneous breathing.

Questions & Answers

Q1ECMO supports oxygenation and ventilation. Which is more related with increase of Edi at the weaning trial?
A1In clinical use, it is difficult to resolve the problem. However I think ventilation is more important than oxygenation, because of following; Edi basically reflects the motion of diaphragm and Edi didn’t reflect for oxygen concentration of ECMO in this case.
Q2How do you measure Edi or conduct the NAVA?
A2First, we insert the dedicated gastric tube. Next we position the electrode on the gastroesophageal junction by the reference to EEG measured the catheter. Additionally, we confirm the depth by chest image. It is the most important to gain the Edi certainly.
Q3Tell me about the position of Edi and the possibility of Edi in clinical use.
A3Some study reported the non-inferiority of NAVA compared Pressure Support. However there are few papers about the Edi as the indicator of breathing workload. Therefore we will collect the data about various cases with respiratory failure.

H.Kawase

The cerebral blood flow threshold for membrane repolarization is not associated with residual cerebral blood flow during ischemic depolarization in rats

It is not known whether the residual CBF during depolarization has an impact on the CBF threshold for membrane repolarization. In the present study, we compared the CBF threshold for repolarization between 2 groups that had different residual CBF values during ischemic depolarization. The threshold for repolarization in the high-flow group was 45.2 ± 7.9%, and that in the low-flow group was 45.0 ± 10.6%. The threshold for repolarization in the high-flow group was not significantly different compared to that in the low-flow group (p = 0.95). CBF during ischemic depolarization does not have an impact on the thresholds for membrane repolarization.

Questions & Answers

Q12 vessel occlusion is the standard method?
A1The method is standard for brain ischemia study.
Q2How about arterial blood gas analysis?
A2We have the data. There is no difference between the two groups.
Q3Is there any difference in blood pressures during 5 minutes ischemic depolarization?
A3We don’t have correct data. I think, blood pressure in the low-flow group was lower than the high-flow group.
Q3Membrane potential during resuscitation is important?
A3Membrane repolarization is required for the recovery of neuronal cell function. So, it is very important.