Effect of thrombomodulin on the development of monocrotaline-induced pulmonary hypertension.
J Anesth
; 28(1): 26-33, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-23817901
ABSTRACT
PURPOSE:
The purpose of the present study was to investigate whether thrombomodulin (TM) prevents the development of pulmonary hypertension (PH) in monocrotaline (MCT)-injected rats.METHODS:
Human recombinant TM (3 mg/kg/2 days) or saline were given to MCT-injected male Sprague-Dawley rats for 19 (n = 14) or 29 (n = 11) days. Control rats (n = 6) were run for 19 days. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy (RVH), percentages of muscularized peripheral arteries (%muscularization), and medial wall thickness of small muscular arteries (%MWT) were measured. To determine inflammatory and coagulation responses, broncho-alveolar lavage fluid (BALF) was analyzed in another set of rats (n = 29). Western blotting for endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS) in the lung tissue was performed in separate rats (n = 13). Survival was determined in 60 rats.RESULTS:
MCT increased mPAP, RVH, %muscularization, and %MWT. TM treatment significantly reduced mPAP, %muscularization, and %MWT in peripheral arteries with an external diameter of 50-100 µm in 19 days after MCT injection, but the effect was lost after 29 days. MCT increased the levels of tumor necrosis factor alpha, monocyte chemoattractant protein-1, and thrombin-antithrombin complex in BALF. Expression of eNOS increased in MCT rats, while peNOS decreased. The relative amount of peNOS to total eNOS increased in MCT/TM rats compared to MCT/Vehicle rats. A Kaplan-Meier survival curve showed no difference with and without TM.CONCLUSION:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Monocrotalina
/
Trombomodulina
/
Hipertensión Pulmonar
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Anesth
Asunto de la revista:
ANESTESIOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón