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Satoshi Gando

Publications and source records attributed to Satoshi Gando.

34 records · Page 2Linked to original sources
PubMed2004

Temporal changes in pulmonary expression of key procoagulant molecules in rabbits with endotoxin-induced acute lung injury: elevated expression levels of protease-activated receptors.

Recently a new concept has emerged implicating thrombin signaling as the "bridge" that connects tissue damage to hemostatic and inflammatory responses. In view of this concept, we hypothesized that induction of protease-activated receptor (PAR) expression may play a critical role in endotoxin-induced tissue injury through the cellular actions of thrombin. Thus, in this study, temporal changes in expression of key precoagulant molecules, including PARs, in lungs from rabbits rendered endotoxemic by 100 microg/kg lipopolysaccharide (LPS) were examined with measurements of variables reflecting acute lung injury (ALI). ALI induction by LPS was confirmed by blood gas derangement, lung vascular hyperpermeability, and histopathological changes, and was characterized by the deposition of fibrin in the alveolar spaces, bronchioles and vessels. Plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) were highly expressed in lungs after LPS injection. While the peaks in levels of PAI-1 and TF were comparable (12 approximately 13-fold from control), their expression time-courses were different: PAI-1 exhibited a bell-shaped expression pattern and peak at 6 h, whereas TF level reached maximum at 10 h. Of note, LPS induced a rapid and significant increase in levels of PAR-1 compared to control, with a peak level at 1 h (3.3-fold). Although declining thereafter, it remained significantly higher than the control level throughout the study period. Expressions of PAR-2, -3, and -4 were also increased by LPS with different time courses from PAR-1 expression. Immunofluorescence staining for PAR-1 were localized in blood vessels, bronchial epithelium, and alveolar pneumocytes after LPS. These results suggest that the increased expression levels of PARs, in addition to PAI-1 and TF, may, in part, underlie the development of ALI occurring during endotoxemia.

Animals↗
PubMed2004

[Systemic inflammatory response syndrome (SIRS) and endothelial cell injury].

During recent years, evidences have been accumulated demonstrating bidirectional crosstalk between coagulation and inflammation. This review outlines the influences that coagulation and inflammation exert on each other to the endothelium and how these systems induce systemic inflammatory response syndrome (SIRS). Then we discussed the implications of leucocyte-endothelial activation to endothelial cell injury followed by multiple organ dysfunction syndrome (MODS) in patients with sustained SIRS. Last we demonstrated an important role of inflammatory circulation disturbance induced by endothelial cell injury for the pathogenesis of MODS in SIRS and sepsis.

Endothelial Cells↗
PubMed2003

Pharmacokinetics and the most suitable dosing regimen of fluconazole in critically ill patients receiving continuous hemodiafiltration.

OBJECTIVE: To evaluate fluconazole pharmacokinetics and the dosage best suited to maintain effective plasma concentration in patients with continuous hemodiafiltration. DESIGN AND SETTING: Prospective study in the general intensive care unit of a university hospital. PATIENTS: Four critically ill patients being treated with fluconazole and receiving continuous hemodiafiltration. INTERVENTIONS: Fluconazole was administered at three dosing regimens: 200 and 400 mg every 24 h, 400 mg every 12 h, and 800 mg every 24 h. MEASUREMENTS AND RESULTS: The following pharmacokinetic variables for fluconazole were obtained: The mean volume distribution of steady state dosed at 400 mg every 12 h and 800 mg every 24 h were 0.55+/-0.23 and 0.71+/-0.16 l/kg, half-life of the elimination phase 8.08+/-0.83 and 9.12+/-0.75 h, total body clearance of fluconazole 1.14+/-0.44 and 0.98+/-0.20 ml/kg per minute, respectively. None of the dosing regimens reached the effective plasma trough concentration of fluconazole; however, simulation study found the recommended dose. CONCLUSIONS: Continuous hemodiafiltration is highly effective in removing fluconazole from circulation. We recommend fluconazole to be dosed at 500-600 mg intravenously every 12 h in patients receiving hemodiafiltration. This dosing regimen resulted in adequate trough plasma levels for systemic fungal infection.

Adult↗
PubMed2003

Contractions to histamine in pulmonary and mesenteric arteries from endotoxemic rabbits: modulation by vascular expressions of inducible nitric-oxide synthase and histamine H1-receptors.

The inducible isoform of nitric-oxide synthase (iNOS) is highly expressed after induction of endotoxemia and contributes to vascular hypocontractility in endotoxemia. Circulating levels of histamine are elevated in animal models of sepsis and in patients with septic shock. This study assessed whether the vascular effects of histamine play a significant role in the pathophysiology of endotoxemic shock despite the hyporesponsiveness to vasoconstrictors associated with iNOS up-regulation. Rabbits were rendered endotoxemic by lipopolysaccharide (LPS; 100 microg/kg, i.v.). In mesenteric arteries taken from animals at 6 h of LPS administration, the contractile response to histamine was significantly impaired but histamine-evoked contractions in pulmonary arteries were unchanged. Western blot revealed a drastic increase in iNOS expression in mesenteric vessels after LPS, but endotoxin-induced iNOS increase was not so marked in pulmonary vessels. On the other hand, expression of endothelial nitric-oxide synthase was suppressed under LPS challenge in both types of vessels. In the presence of NG-nitro-l-arginine or (S)-ethylisothiourea used for iNOS inhibition, histamine-evoked contractions of endotoxemic pulmonary and mesenteric vessels were significantly enhanced. This was possibly associated with a dramatic increase in H1-receptor expression at the gene and protein levels, as determined by Northern blot and immunoblot analyses. Furthermore, we found that LPS-induced endotoxemia caused prominent increases in production of histamine through induction of histidine decarboxylase in tissues, including blood vessels. From these results, we propose that histamine may contribute to the development of endotoxin-induced pulmonary hypertension.

Animals↗
PubMed2003

Normalization by edaravone, a free radical scavenger, of irradiation-reduced endothelial nitric oxide synthase expression.

We investigated the therapeutic effect of edaravone, a free radical scavenger, on alterations in endothelium-dependent relaxation and endothelial nitric oxide synthase (eNOS) expression in the rabbit ear central artery at 2 weeks after exposure to a dose of 45 Gy radiation with a cobalt60 unit. For treatment with edaravone, edaravone was given daily to the animals from the day before irradiation at an intrapenetreal dose of 10 mg/kg twice a day. The endothelium-dependent relaxant response to acetylcholine was markedly impaired in irradiated vessels. Edaravone treatment improved the response to the level observed in nonirradiated control vessels. Using immunohistochemical and Western blot techniques, we showed that protein expression of eNOS in irradiated vessels was reduced to about 50% of control and that edaravone treatment returned it nearly to intact levels. Gene expression of eNOS, analyzed by reverse transcription-competitive polymerase chain reaction, was found to be reduced from the control level by 47% following irradiation. The reduced level of eNOS mRNA in irradiated vessels was almost completely normalized by edaravone treatment. These results suggest that edaravone has a protective effect on the reduced expression of eNOS and its associated endothelial cell dysfunction in the vessels following irradiation. We thus assume that oxygen-free radicals may be closely related to the irradiation-induced derangement of the eNOS gene regulation.

Acetylcholine↗
PubMed2003

Imbalances between the levels of tissue factor and tissue factor pathway inhibitor in ARDS patients.

INTRODUCTION: To evaluate the pathogenetic role of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and neutrophil elastase in acute respiratory distress syndrome (ARDS), as well as to test the hypothesis that TFPI levels modified by neutrophil activation are not sufficient to prevent TF-dependent intravascular coagulation, leading to sustained systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), which determine the prognosis of these patients. MATERIALS AND METHODS: The study subjects consisted of 55 patients with trauma and sepsis who were divided into three groups according to the Lung Injury Score. Ten normal healthy volunteers served as control. Plasma levels of TF, TFPI, and neutrophil elastase were measured on the day of injury or the day of diagnosis of sepsis (day 0) and days 1 through 4. The number of SIRS criteria that the patient met and the disseminated intravascular coagulation (DIC) score is determined daily. RESULTS: Patients (15) developed ARDS, 23 were at risk for but did not develop the syndrome, and 17 patients were without risk for ARDS. TF and neutrophil elastase levels in ARDS patients were persistently higher than those in other two groups and control subjects. However, the TFPI levels showed no difference among the three groups, which retained normal or slightly elevated levels compared to the control subjects. DIC scores did not improve and SIRS continued during the study period in patients with ARDS. The ARDS patients showed higher numbers of dysfunctioning organs and associated with poorer outcome than the other two groups. CONCLUSION: Systemic activation of the TF-dependent pathway not adequately balanced by TFPI is one of the aggravating factors of ARDS. High levels of neutrophil elastase released from activated neutrophils may explain the imbalance of TF and TFPI. Persistent DIC and sustained SIRS contribute to MODS, determining the prognosis of ARDS patients.

Disseminated Intravascular Coagulation↗
PubMed2003

The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release?

UNLABELLED: The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation. IMPLICATIONS: The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.

Animals↗
PubMed2003

[Coagulofibrinolytic response to surgical insult].

During recent years, evidence has accumulated demonstrating bidirectional cross-talk in the classic neuroendocrine response as well as immune-mediated inflammatory response, and newly described coagulofibrinolytic response. This review outlines the influences that these systems exert on each other and discusses the implications of the coagulofibrinolytic response to the multiple-organ dysfunction syndrome (MODS) and patient prognosis. The results of the physiological coagulofibrinolytic response to physical insults such as surgery and trauma are hemostasis and wound healing. We stress that this response is nonspecific and is similar in all types of insult without exception. An abnormal hemostatic response to surgical insult is called disseminated intravascular coagulation (DIC). DIC associated with the sustained systemic inflammatory response syndrome (SIRS) in postsurgical insult leads to the development of MODS, which is the main determinant of patient outcome. To prevent the progression of DIC, new drugs like activated protein C which can control both coagulation and inflammation now appear promising.

Blood Coagulation↗
PubMed2002

Hemodynamic significance of histamine synthesis and histamine H1- and H2-receptor gene expression during endotoxemia.

The hypothesis that endotoxemia may modify histamine synthesis or histamine receptor expression and that these changes may contribute to cardiovascular dysfunction was tested in rabbits which were rendered endotoxemic by lipopolysaccharide (LPS; 100 micro g/kg, i.v.). The plasma histamine concentration was elevated shortly after LPS, remaining elevated (a 50-fold increase) over the experimental period of 6 h. The sustained increase in plasma histamine was associated with a time-dependent increase in expression of histidine decarboxylase (HDC) in different tissues including atrium, as determined by Western blot analysis. The H(1)-receptor antagonist diphenhydramine significantly shortened the duration of the initial hypotension and the H(2)-receptor antagonist ranitidine greatly suppressed the lasting tachycardia following LPS injection. Northern blot analysis showed that LPS dramatically induced gene expressions of histamine H(1)- and H(2)-receptors in cardiac tissues. In right atrium isolated from the septic animal, the positive chronotropic effect of histamine was significantly diminished. This was possibly due to a marked reduction in G(s)(alpha) protein expression, indicating the impaired H(2)-receptor cellular signaling. In conclusion, LPS-induced endotoxemia causes prominent increases in production of histamine through induction of HDC and in gene expression of histamine receptors. We suggest that overproduction of histamine may be partly responsible for the hemodynamic alterations of endotoxemia.

Animals↗
PubMed2002

Abdominal compartment syndrome and intrahepatic portal venous gas: a possible complication of endoscopy.

OBJECTIVE: We report the first patient to developed abdominal compartment syndrome (ACS) with intrahepatic portal venous gas (IHPVG) and pneumatosis cystoides intestinalis following emergency upper gastrointestinal endoscopy. CASE PRESENTATION: A 53-year-old man underwent an emergency upper gastrointestinal endoscopy for suspicion of upper gastrointestinal bleeding. The patient developed intra-abdominal hypertension and ACS associated with IHPVG after the endoscopy. Although the patient developed severe shock following ACS, he was managed conservatively and successfully recovered. CONCLUSIONS: An emergency upper gastrointestinal endoscopy may be associated with intra-abdominal hypertension and ACS. Our report provides an additional case of a survivor who required no surgical intervention for ACS and IHPVG following endoscopy.

Abdomen↗
PubMed2002

Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis.

OBJECTIVE: To determine the precise relationship among tissue factor, tissue factor pathway inhibitor (TFPI), and neutrophil elastase in sepsis, as well as to test the hypothesis that low TFPI concentrations are not sufficient to prevent tissue factor-dependent intravascular coagulation, leading to multiple organ dysfunction syndrome and death. DESIGN: Prospective, cohort study. SETTING: General intensive care unit of tertiary care emergency department. PATIENTS: Thirty-one consecutive patients with sepsis, classified as 15 survivors and 16 nonsurvivors. Ten normal, healthy volunteers served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration (tissue factor), TFPI, neutrophil elastase, and global variables of coagulation and fibrinolysis were measured on the day of diagnosis of sepsis, severe sepsis, and septic shock and days on 1-4 after diagnosis. The number of systemic inflammatory response syndrome criteria that patients met and the disseminated intravascular coagulation score were determined simultaneously. The results of these measurements were compared between the survivors and the nonsurvivors. In the nonsurvivors, significantly higher concentrations of tissue factor and neutrophil elastase were found compared with the survivors and control subjects. However, the TFPI values showed no difference between the two groups. No correlation was found between the peak concentrations of tissue factor and TFPI. Disseminated intravascular coagulation scores and numbers of the SIRS criteria met by the survivors significantly decreased from day 0 to day 4, but those of the nonsurvivors did not improve during the study period. The nonsurvivors showed thrombocytopenia and higher numbers of dysfunctioning organs than did the survivors. CONCLUSIONS: We systematically elucidated the relationship between tissue factor and TFPI in patients with sepsis, severe sepsis, and septic shock. Activation of tissue factor-dependent coagulation pathway not adequately balanced by TFPI has important roles in sustaining DIC and systemic inflammatory response syndrome, and it contributes to multiple organ dysfunction syndrome and death. High concentrations of neutrophil elastase released from activated neutrophils may explain, in part, the imbalance of tissue factor and TFPI in sepsis.

Adult↗
PubMed2002

[The past and the future prospects of acute medicine].

Recent development and the future prospects of acute medicine as well as emergency medical treatment system in Japan are reviewed. At first, I described the history of medical system, transporting system, and information system in the emergency medical treatment system, and then strongly emphasized the practical use of this system. The base of the system was constructed in the middle 1970s and has greatly developed during recent two decades. The development of the emergency medical treatment system could let us know an important role of the education of acute medicine for medical students in the university. Now a lot of medical student can learn acute medicine at university in our country. The education of acute medicine should be expanded to nurses, comedical stuffs, ambulant teams, and the citizens who are the constituent member of the prehospital care. Based on the establishment of emergency medical treatment system and the spread of acute medicine, I believe that Japanese people can get an affluent and safety life. I hope more development of emergency medical treatment system and acute medicine in the 21st century.

Emergency Medical Services↗
PubMed2002

Combined activation of coagulation and inflammation has an important role in multiple organ dysfunction and poor outcome after severe trauma.

We tested the hypothesis that activated neutrophil-endothelial cell interaction in DIC can cause endothelial injury contributing to multiple organ dysfunction syndrome (MODS) and a poor outcome after trauma. Fifty-eight severe trauma patients, 29 with DIC and 29 without DIC were studied. Serial levels of soluble L-, P-, and E-selectins, ICAM-1, VCAM-1, thrombomodulin, and neutrophil elastase were measured on days 0-4 after trauma. The numbers of systemic inflammatory response syndrome (SIRS) criteria that patients met were determined, simultaneously. In the DIC patients, higher DIC scores, lower platelet counts, and a longer duration of SIRS were found compared with the non-DIC patients. The incidence of ARDS and MODS were higher in patients with DIC than in those patients without DIC, and the DIC patients had poor outcome. Soluble L-selectin (sL-selectin) level on Day 1 in the DIC patients who died was markedly lower than those in the non-DIC patients. The levels of sP- and sE-selectins, sICAM-1, and sVCAM-1 were more elevated in the patients with DIC than in those without DIC on days 2 to 4. Neutrophil elastase and sThrombomodulin levels in the DIC patients persistently increased during the study period compared to those in the non-DIC patients. Maximum DIC scores in the DIC group showed good correlations with peak levels of sICAM-1, sVCAM-1, neutrophil elastase, sThrombomodulin, and the number of dysfunctioning organs. Highly activated and sustained inflammation caused by neutrophil-endothelium interaction in DIC gives rise to MODS and poor outcome in patients with severe trauma. These results suggest a close relationship between inflammation and thrombosis in posttrauma DIC.

Adult↗
PubMedDate not supplied

Pharmacokinetics and the most suitable regimen of panipenem/beta mipron in critically ill patients receiving continuous renal replacement therapy: a pilot study.

Critically ill patients often have complications of acute renal failure induced by severe infection or sepsis. The patients need administration of broad-spectrum antibiotics as well as continuous renal replacement therapy (CRRT). However, there is no uniform pharmacokinetics of antibiotics during the CRRT because CRRT is performed with the various combinations of dialysate flows (QD) and ultrafiltrate flows (QF). The aims of this study were to estimate the pharmacokinetics of panipenem/beta Mipron (PAPM/BP) and to determine the appropriate treatment regimens for PAPM/BP in critically ill patients undergoing CRRT. In patients with CRRT, the PAPM total clearance (PAPM CLtot) was calculated as the sum of PAPM clearance dependent on the living body and CRRT and shown as follows:PAPM CLtot (ml/min) = (1.2 CLcre + 66.5) + 0.86 (QD + QF) where CLcre is creatinine clearance. Pharmacokinetic values of PAPM were measured in 4 patients with CRRT. According to these results, the most appropriate treatment regimen regarding PAPM CLtot (ml/min) showed as follows:PAPM CLtot < 80 0.5 g every 12 hours or 1 g every 15 hoursPAPM CLtot 80 to 120 0.5 g every 8 hours or 1 g every 12 hoursPAPM CLtot 120 to 160 0.5 g every 6 hours or 1 g every 8 hours.

Acute Kidney Injury↗