Effect of thrombomodulin on the development of monocrotaline-induced pulmonary hypertension

Yamada, Yasuharu; Maruyama, Junko; Zhang, Erquan; Okada, Amphone; Yokochi, Ayumu; Sawada, Hirofumi; Mitani, Yoshihide; Hayashi, Tatsuya; Suzuki, Koji; Maruyama, Kazuo

doi:10.1007/s00540-013-1663-z

Cited by 17 publications

(34 citation statements)

References 31 publications

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“…In contrast, the activity of eNOS as represented by a proportion of phosphorylated eNOS over total eNOS is decreased from the early stage of PH development. 20,21 Identical timedependent alterations in the eNOS profile were also observed in a hypoxia-induced PH rat model. 18 It is therefore speculated that decreased eNOS activity is related to further progression of PH.…”

Section: Discussionmentioning

confidence: 73%

Single-dose rosuvastatin ameliorates lung ischemia–reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension

Matsuo

Saiki

Adachi

et al. 2015

The Journal of Thoracic and Cardiovascular Surgery

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Section: Discussionmentioning

confidence: 73%

Single-dose rosuvastatin ameliorates lung ischemia–reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension

Matsuo

Saiki

Adachi

et al. 2015

The Journal of Thoracic and Cardiovascular Surgery

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“…Gyanesh et al .,[28] compared intranasal dexmedetomidine (1 μg kg −1 ) and ketamine (5 μg kg −1 ) for procedural sedation in children undergoing an MRI. There were no significant differences in the children's response to administration of the drug and IV cannulation between dexmedetomidine and ketamine.…”

Section: Discussionmentioning

confidence: 99%

A prospective, randomized, double blinded comparison of intranasal dexmedetomodine vs intranasal ketamine in combination with intravenous midazolam for procedural sedation in school aged children undergoing MRI

Ibrahim

2014

Anesth Essays Res

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Background:For optimum magnetic resonance imaging (MRI) image quality and to ensure precise diagnosis, patients have to remain motionless. We studied the effects of intranasal dexmedetomidine and ketamine with intravenous midazolam for pre-procedural and procedural sedation in school aged children.Patients and Methods:Children were randomly allocated to one of two groups: (Group D) received intranasal dexmedetomidine 3 μg kg–1 and (Group K) received intranasal ketamine 7 mg kg–1. Sedation levels 10, 20 and 30 min after drug instillation were evaluated using a Modified Ramsay sedation scale. A 4-point score was used to evaluate patients when they were separated from their parents and their response to intravenous cannulation.Results:The two groups were comparable in terms of the child's anxiety at presentation (P = 0.245). We observed that Group K achieved faster sedation at 10 min point with P < 0.05. A comparable sedation score at 20 and 30 min were noted. The two groups were comparable regarding to the child's acceptance of nasal administration (P = 0.65). The sedation failure rate was insignificantly differ between groups (13.7% vs. 20.6% for Group D and K respectively). Heart rate and systolic blood pressure showed a significant difference between the two groups starting from the point of 20 min.Conclusion:Intranasal dexmedetomidine 3 μg kg–1 or ketamine 7 mg kg–1 can be used safely and effectively to induce a state of moderate conscious sedation and to facilitate parents’ separation and IV cannulation. Addition of midazolam in a dose not sufficient alone to produce the target sedation achieved our goal of deep level of sedation suitable for MRI procedure.

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“…Although rhTM is administered via the intravenous route in clinical settings, it is difficult to place a venous catheter in neonatal mice; therefore, we chose subcutaneous administration in this study. Based on the pharmacological kinetic data for rhTM 20 , we subcutaneously administered it at 6 h prior to sepsis induction, which achieved a sufficient blood concentration in adult rats. Based on the above, we think this result reflects the protocol used for clinical rhTM therapy using the intravenous route at the onset of sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…The timing of rhTM SC administration was determined based on a pharmacokinetic study to achieve a peak concentration at sepsis induction. In a pharmacokinetic study of adult rats, a single subcutaneous injection of 3.0 mg/kg of rhTM increased blood concentration slowly, such that it reached sufficient levels between 3 and 9 hours after administration 20 . At 6 h after rhTM administration, sepsis was induced by IP administration of 1.5 mg/g body weight (BW) CS; BW changes and survival were then monitored for 7 days.…”

Section: Recombinant Human Thrombomodulin (Rhtm) Treatmentmentioning

confidence: 99%

Recombinant human thrombomodulin attenuated sepsis severity in a non-surgical preterm mouse model

Ashina

Fujioka

Nishida

et al. 2020

Sci Rep

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neonatal sepsis is characterised by dysregulated immune responses. Lipid mediators (LMs) are involved in the regulation of inflammation. Human recombinant thrombomodulin (rhTM), an anticoagulant, has anti-inflammatory effects and might be useful for sepsis treatment. A stock caecal slurry (CS) solution was prepared from adult caeca. To induce sepsis, 1.5 mg/g of CS was administered intraperitoneally to 4 d-old wild-type FVB mouse pups. Saline (Veh-CS) or rhTM (3 or 10 mg/kg; rhTM3-CS or rhTM10-CS) was administered subcutaneously 6 h prior to sepsis induction, and liver LM profiles at 3 and 6 h postsepsis induction and survival up to 7 days were examined. Mortality was significantly lower (47%) in the rhTM3-CS group and significantly higher (100%) in the rhTM10-CS group, compared with the Veh-CS group (79%, p < 0.05). Eleven LMs (12-HEPE, EPA, 14-HDHA, DHA, PD1, PGD 2 , 15d-PGJ 2 , 12S-HHT, lipoxin B 4 , 12-HETE, AA) were significantly increased at 3 h, and five LMs (5-HEPE, 15-HEPE, 18-HEPE, 17-HDHA, PD1) were significantly increased at 6 h post-sepsis induction. Increased EPA, DHA, 12S-HHT, lipoxin B 4 , and AA were significantly suppressed by rhTM pre-treatment. rhTM was protective against neonatal sepsis. This protective effect might be mediated via LM modulation. Further post-sepsis studies are needed to determine clinical plausibility.

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Effect of thrombomodulin on the development of monocrotaline-induced pulmonary hypertension

Abstract: Although the administration of TM might slightly delay the progression of MCT-induced PH, the physiological significance for treatment is limited, since the survival rate was not improved.

Cited by 17 publications

References 31 publications

Single-dose rosuvastatin ameliorates lung ischemia–reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension

Single-dose rosuvastatin ameliorates lung ischemia–reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension

A prospective, randomized, double blinded comparison of intranasal dexmedetomodine vs intranasal ketamine in combination with intravenous midazolam for procedural sedation in school aged children undergoing MRI

Recombinant human thrombomodulin attenuated sepsis severity in a non-surgical preterm mouse model

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