Faculty Profiles - MORIMATSU Hiroshi

MISC - MORIMATSU Hiroshi

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Heme arginate pretreatment attenuates pulmonary NF-κB and AP-1 activation induced by hemorrhagic shock via heme oxygenase-1 induction

T. Sasaki, Takatoru Takahashi, H. Shimizu, Y. Toda, H. Morimatsu, M. Takeuchi, M. Yokoyama, R. Akagi, K. Morita

Medicinal Chemistry 2 ( 3 ) 271 - 274 2006.5

Language：English

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors
nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-κB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-κB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-κB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-κB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors. © 2006 Bentham Science Publishers Ltd.

DOI： 10.1263/jbb.101.271

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成人心臓血管手術後症例における呼気一酸化炭素(CO)濃度の上昇

森松博史, 高橋徹, 竹内護, 戸田雄一郎, 松崎孝, 森田潔

Shock : 日本Shock学会雑誌 21 ( 1 ) 56 - 56 2006.4

ウリナスタチンはラット出血性ショック後急性肺傷害を改善する

井上一由, 高橋徹, 井戸加奈, 川上朋子, 森松博史, 森田潔

Shock : 日本Shock学会雑誌 21 ( 1 ) 46 - 46 2006.4

Increased heme catabolism in critically ill patients: correlation among exhaled carbon monoxide, arterial carboxyhemoglobin, and serum bilirubin IX alpha concentrations

H Morimatsu, T Takahashi, K Maeshima, K Inoue, T Kawakami, H Shimizu, M Takeuchi, M Yokoyama, H Katayama, K Morita

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 290 ( 1 ) L114 - L119 2006.1

Language：English Publisher：AMER PHYSIOLOGICAL SOC

It has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there was no study that examined correlation among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and bilirubin IX alpha (BR) in serum, i.e., the three major indexes of heme catabolism, within the same subject. Here, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in eight healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared with control. There was significant correlation between CO and CO-Hb and CO and total BR level. We also found CO concentrations correlated with indirect BR but not direct BR. Multivariate linear regression analysis for amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of study subjects were markedly heterogeneous. We found no correlation among exhaled CO, patients' severity, and degree of inflammation, but we found a strong trend of a higher exhaled CO concentration in survivors than in nonsurvivors. These findings suggest there is an increased heme breakdown in critically ill patients and that exhaled CO concentration, arterial CO-Hb, and serum total BR concentrations may be useful markers in critically ill conditions.

DOI： 10.1152/ajplung.00031.2005

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Pulmonary artery catheter versus pulse contour analysis: a prospective epidemiological study

Shigehiko Uchino, Rinaldo Bellomo, Hiroshi Morimatsu, Makoto Sugihara, Craig French, Dianne Stephens, Julia Wendon, Patrick Honore, John Mulder, Andrew Turner

CRITICAL CARE 10 ( 6 ) 2006

Language：English Publisher：BIOMED CENTRAL LTD

Introduction The choice of invasive systemic haemodynamic monitoring in critically ill patients remains controversial as no multicentre comparative clinical data exist. Accordingly, we sought to study and compare the features and outcomes of patients who receive haemodynamic monitoring with either the pulmonary artery catheter (PAC) or pulse contour cardiac output (PiCCO) technology.
Methods We conducted a prospective multicentre, multinational epidemiological study in a cohort of 331 critically ill patients who received haemodynamic monitoring by PAC or PiCCO according to physician preference in intensive care units (ICUs) of eight hospitals in four countries. We collected data on haemodynamics, demographic features, daily fluid balance, mechanical ventilation days, ICU days, hospital days, and hospital mortality. We statistically compared the two techniques.
Results Three hundred and forty-two catheters ( PiCCO 192 and PAC 150) were inserted in 331 patients. On direct comparison, patients with PAC were older ( 68 versus 64 years of age; p = 0.0037), were given inotropic drugs more frequently 37.3% versus 13%; p < 0.0001), and had a lower cardiac index (2.6 versus 3.2 litres/ minute per square meter; p < 0.0001). Mean daily fluid balance was significantly greater during PiCCO monitoring (+ 659 versus + 350 ml/day; p = 0.017) and mechanical ventilation-free days were fewer ( 12 for PiCCO versus 21 for PAC; p = 0.045). However, after multiple regression analysis, we found no significant effect of monitoring technique on mean daily fluid balance, mechanical ventilation-free days, ICU-free days, or hospital mortality. A secondary multiple logistic regression analysis for hospital mortality which included mean daily fluid balance showed that positive fluid balance was a significant predictor of hospital mortality ( odds ratio = 1.0002 for each ml/day; p = 0.0073).
Conclusion On direct comparison, the use of PiCCO was associated with a greater positive fluid balance and fewer ventilator-free days. After correction for confounding factors, the choice of monitoring did not influence major outcomes, whereas a positive fluid balance was a significant independent predictor of outcome. Future studies may best be targeted at understanding the effect of pursuing different fluid balance regimens rather than monitoring techniques per se.

DOI： 10.1186/cc5126

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【これまでのそしてこれからの循環動態モニタリング】胸郭インピーダンス法

森松博史, 竹内護, 下野綾子, 戸田雄一郎, 森田潔

ICUとCCU 30 ( 3 ) 203 - 206 2006

先天性表皮水疱症の食道狭窄に対するバルーン拡張術の麻酔経験

松三絢弥, 森松博史, 松崎孝, 戸田雄一郎, 中塚秀輝, 森田潔

麻酔 55 ( 3 ) 362 - 364 2006

[急性血液浄化法徹底ガイド] 最近注目されている血液浄化法 High folw CHDF,High volume CHF

片山浩, 森松博史, 江木盛時, 岡部悠吾, 佐藤哲文, 森田潔

救急・集中治療 2006

Non Renal Indicationによる血液浄化法の考察

森松博史

ICUとCCU 30 ( 8 ) 541 - 545 2006

ストレス蛋白Heme Oxygenase-1(HO-1)の腎および腸管保護作用

高橋徹, 森松博史, 森田潔

ICUとCCU 30 ( 5 ) 359 - 365 2006

ドパミン神話の崩壊？ドパミンのない世界へようこそ

森松博史

Cardiovascular Anesthesia 2006

血液浄化と酸塩基平衡

森松博史, 江木盛時, 片山浩

救急・集中治療 2006

生体肝移植術後の敗血症症例にPMX‐DHPを施行した1例

佐藤哲文, 片山浩, 松三絢弥, 松崎孝, 新井美奈子, 竹中央, 森松博史, 賀来隆治, 佐藤健治, 中塚秀輝, 松三昌樹, 森田潔

エンドトキシン血症救命治療研究会誌 9 ( 1 ) 212 - 217 2005.12

The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy

M Yokoyama, Y Itano, H Katayama, H Morimatsu, Y Takeda, T Takahashi, O Nagano, K Morita

ANESTHESIA AND ANALGESIA 101 ( 5 ) 1521 - 1527 2005.11

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

We investigated whether perioperative extensive epidural block (C3-L) affects postoperative immune response in patients undergoing radical esophagectomy. Patients undergoing radical esophagectomy were randomly assigned to either general anesthesia with continuous epidural infusion via 2 epidural catheters that was continued for postoperative analgesia (group E, n = 15) or intraoperative general anesthesia and postoperative IV morphine analgesia (group G, n = 15). Plasma levels of stress hormones, cytokines, C-reactive protein (CRP), leukocyte counts, and distribution of lymphocyte subsets were assessed before and after surgery and on postoperative days (PODs) 1 and 3. In comparison with group E, significant increases in plasma epinephrine level at the end of surgery (P < 0.05) and norepinephrine level at the end of surgery (P < 0.01) and on POD1 (P < 0.01) and POD3 (P < 0.01) and significant decrease in cluster of differentiation (CD4/CD8 ratio) at the end of surgery (P < 0.05) were observed in group G. However, there were no significant differences in other variables between groups. In both groups, plasma cortisol, adrenocorticotropic hormone, interleukin (IL)-1 beta, IL-6, IL-10, and CRP levels were increased after surgery (each group P < 0.01) and IL-1 beta, IL-6, IL-10, and CRP were still increased on POD1 and POD3 (each change, each group P < 0.01). Leukocyte counts were increased on PODI (each group P < 0.05) and POD3 (each group P < 0.01). The proportion of lymphocytes decreased from the end of surgery to POD3 (each group P < 0.01). The proportion of B cells was increased on POD1 (each group P < 0.01); that of natural killer cells was decreased at PODI and POD3 (each group P < 0.01). We conclude that tissue damage and inflammation apparently overcome the effects of extensive epidural block on stress response and immune function in radical esophagectomy.

DOI： 10.1213/01.ANE.0000184287.15086.1E

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集中治療に役立つ血液浄化の最先端:HF,HV‐CHDFに対する期待と展望

片山浩, 森松博史, 佐藤哲文, 岩崎達雄, 武田吉正, 竹内護, 中塚秀輝, 森田潔

日本臨床麻酔学会誌 25 ( 6 ) S148 2005.10

External validation of severity scoring systems for acute renal failure using a multinational database

S Uchino, R Bellomo, H Morimatsu, S Morgera, M Schetz, Tan, I, C Bouman, E Macedo, N Gibney, A Tolwani, GS Doig, HO van Straaten, C Ronco, JA Kellum

CRITICAL CARE MEDICINE 33 ( 9 ) 1961 - 1967 2005.9

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objective. Several different severity scoring systems specific to acute renal failure have been proposed. However, most validation studies of these scoring systems were conducted in a single center or in a small number of centers, often the same ones used for their development. Therefore, it is not known whether such severity scoring systems may be widely applied.
Design: Prospective clinical investigation.
Setting: Intensive care units.
Patients: One thousand seven hundred and forty-two intensive care unit patients with acute renal failure who were either treated with renal replacement therapy or fulfilled predefined criteria.
Interventions: Demographic and clinical information and outcomes were measured.
Measurements and Main Results. Scores for four acute renal failure-specific scoring systems and two general scoring systems (Simplified Acute Physiology Score II and Sequential Organ Failure Assessment) were calculated, and their discrimination and calibration were tested with receiver operating characteristic curves and Hosmer-Lemeshow goodness-of fit-tests. For the receiver operating characteristic curves, blood lactate levels were also used as a reference. All scores had an area under the receiver operating characteristic curve < 0.7 (Mehta 0.670, Liano 0.698, Chertow 0.610, Paganini 0.643, Simplified Acute Physiology Score II 0.645, Sequential Organ Failure Assessment 0.675, lactate 0.639). For scores that can calculate predicted mortality, the Hosmer-Lemeshow goodness-of-fit test showed poor calibration.
Conclusions: None of the scoring systems tested had a high level of discrimination or calibration to predict mortality for patients with acute renal failure when tested in a broad cohort of patients from multiple countries. A large, multiple-center database might be needed to improve the discrimination and calibration of acute renal failure scoring system.

DOI： 10.1097/01.CCM.0000172279.66229.07

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Acute renal failure in critically ill patients - A multinational, multicenter study

S Uchino, JA Kellum, R Bellomo, GS Doig, H Morimatsu, S Morgera, M Schetz, Tan, I, C Bouman, E Macedo, N Gibney, A Tolwani, C Ronco

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 294 ( 7 ) 813 - 818 2005.8

Language：English Publisher：AMER MEDICAL ASSOC

Context Although acute renal failure (ARF) is believed to be common in the setting of critical illness and is associated with a high risk of death, little is known about its epidemiology and outcome or how these vary in different regions of the world.
Objectives To determine the period prevalence of ARF in intensive care unit (ICU) patients in multiple countries; to characterize differences in etiology illness severity, and clinical practice; and to determine the impact of these differences on patient outcomes.
Design, Setting, and Patients Prospective observational study of ICU patients who either were treated with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries.
Main Outcome Measures Occurrence of ARF, factors contributing to etiology, illness severity, treatment, need for renal support after hospital discharge, and hospital mortality.
Results Of 29 269 critically ill patients admitted during the study period, 1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their ICU stay, including 1260 who were treated with RRT. The most common contributing factor to ARF was septic shock (47.5%; 95% Cl, 45.2%-49.5%). Approximately 30% of patients had preadmission renal dysfunction. Overall hospital mortality was 60.3% (95% Cl, 58.0%-62.6%). Dialysis dependence at hospital discharge was 13.8% (95% Cl, 11.2%-16.3%) for survivors. Independent risk factors for hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95% Cl, 1.50-2.55; P<.001), mechanical ventilation (OR, 2.11; 95% Cl, 1.58-2.82; P<.001), septic shock (OR, 1.36; 95% Cl, 1.03-1.79; P=.03), cardiogenic shock (OR, 1.41; 95% Cl, 1.05-1.90; P=.02), and hepatorenal syndrome (OR, 1.87; 95% Cl, 1.07-3.28; P=.03).
Conclusion In this multinational study; the period prevalence of ARF requiring RRT in the ICU was between 5% and 6% and was associated with a high hospital mortality rate.

DOI： 10.1001/jama.294.7.813

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A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study

J Makino, S Uchino, H Morimatsu, R Bellomo

CRITICAL CARE 9 ( 4 ) R357 - R362 2005.8

Language：English Publisher：BIOMED CENTRAL LTD

Introduction Metabolic acidosis is common in patients with cardiac arrest and is conventionally considered to be essentially due to hyperlactatemia. However, hyperlactatemia alone fails to explain the cause of metabolic acidosis. Recently, the Stewart Figge methodology has been found to be useful in explaining and quantifying acid - base changes in various clinical situations. This novel quantitative methodology might also provide useful insight into the factors responsible for the acidosis of cardiac arrest. We proposed that hyperlactatemia is not the sole cause of cardiac arrest acidosis and that other factors participate significantly in its development.
Methods One hundred and five patients with out-of-hospital cardiac arrest and 28 patients with minor injuries ( comparison group) who were admitted to the Emergency Department of a tertiary hospital in Tokyo were prospectively included in this study. Serum sodium, potassium, ionized calcium, magnesium, chloride, lactate, albumin, phosphate and blood gases were measured as soon as feasible upon arrival to the emergency department and were later analyzed using the Stewart - Figge methodology.
Results Patients with cardiac arrest had a severe metabolic acidosis ( standard base excess - 19.1 versus - 1.5; P < 0.0001) compared with the control patients. They were also hyperkalemic, hypochloremic, hyperlactatemic and hyperphosphatemic. Anion gap and strong ion gap were also higher in cardiac arrest patients. With the comparison group as a reference, lactate was found to be the strongest determinant of acidosis (- 11.8 meq/ l), followed by strong ion gap (- 7.3 meq/ l) and phosphate (- 2.9 meq/ l). This metabolic acidosis was attenuated by the alkalinizing effect of hypochloremia (+ 4.6 meq/ l), hyperkalemia (+ 3.6 meq/ l) and hypoalbuminemia (+ 3.5 meq/ l).
Conclusion The cause of metabolic acidosis in patients with out-of-hospital cardiac arrest is complex and is not due to hyperlactatemia alone. Furthermore, compensating changes occur spontaneously, attenuating its severity.

DOI： 10.1186/cc3714

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重症患者における呼気一酸化炭素濃度(CO)と臓器不全との関係

森松博史, 高橋徹, 井戸佳奈, 川上朋子, 前島亨一郎, 戸田雄一郎, 清水裕子, 森田潔

Shock : 日本Shock学会雑誌 20 ( 1 ) 44 - 44 2005.4

Exhaled CO after surgery: A consequence of postoperative narcotics? - Response

H Morimatsu, T Takahashi

ANESTHESIA AND ANALGESIA 100 ( 3 ) 896 - 896 2005.3

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