PMID- 23786934
OWN - NLM
STAT- MEDLINE
DCOM- 20140430
LR  - 20130621
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 126
IP  - 12
DP  - 2013 Jun
TI  - Effect of low-molecular-weight heparin and urokinase on pulmonary arteries 
      involved in pulmonary embolism.
PG  - 2254-9
AB  - BACKGROUND: Pulmonary embolism (PE) is a common and often fatal disease. Early 
      after pulmonary thromboembolism, inflammation and associated intimal hyperplasia 
      occur within the pulmonary arteries, similar to what is observed with chronic 
      thromboembolic pulmonary hypertension. This study tested the hypothesis that 
      thrombolytic and anticoagulant agents would have anti-inflammatory effects or 
      inhibit intimal hyperplasia of involved pulmonary arteries. METHODS: Seventy-two 
      male New Zealand white rabbits were randomly divided into two groups (54 rabbits 
      in the PE group and 18 in the sham group). Experimental PE was induced in 54 
      rabbits by femoral vein injection of autologous blood clots and confirmed with 
      pulmonary angiography, and other 18 rabbits underwent sham operations. Fifty-four 
      rabbits in the PE group were randomly divided into three groups: a control group 
      (treated with normal saline), a low-molecular- weight heparin (LMWH) group 
      (treated with LMWH), and a urokinase (UK) group (treated with UK). Arterial blood 
      gas was analyzed at 2, 7, and 28 days (n = 6 per time point by random group 
      division), then lung tissues were removed and were analyzed for pro-inflammatory 
      cytokines and chemokines, and were stained for intimal hyperplasia. RESULTS: The 
      overall survival of rabbits undergoing PE was 100%. PE distribution detected on 
      digital signal angiography (DSA) and histopathology was shown in 67% of rabbits 
      (36/54) in the bilateral low lobar pulmonary arteries (PAs). The results showed 
      that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) 
      significantly increased and PO2 decreased in the control group compared with the 
      sham group. Compared with controls, the UK group had a decreased level of PA-aO2 
      on day 2 (P < 0.05), however, there was no significant difference in the LMWH 
      group. Compared with controls, the LMWH group had a decreased level of monocyte 
      chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 
      and 28 (P < 0.05), and the UK group had decreased levels on days 2 and 7 (P < 
      0.05). Compared with sham group, all PE groups had an increased level of 
      interleukin-13 (IL-13) and transforming growth factor-beta (TGF-beta) in unaffected 
      lung tissue samples at days 2 and 7. IL-13 in affected lung tissue in the LMWH 
      group was decreased at all time points compared with controls (P < 0.05). 
      However, TGF-beta in affected lung tissue of the LMWH and UK groups increased at day 
      28. There was less intimal hyperplasia in involved pulmonary arteries at days 7 
      and 28 in the LMWH group compared with controls; there was no statistical 
      difference in the UK group compared with controls. CONCLUSIONS: UK treatment can 
      rapidly improve the V/Q mismatch in PE and appears a short-term anti-inflammatory 
      benefit. However, LMWH maybe inhibit the later local inflammatory reaction and 
      reduce intimal hyperplasia.
FAU - Wu, Jun-Ping
AU  - Wu JP
AD  - Graduate School of Tianjin Medical University, Tianjin 300070, China.
FAU - Sun, Xin
AU  - Sun X
FAU - Wu, Qi
AU  - Wu Q
FAU - DU, Zhong-Zhen
AU  - DU ZZ
FAU - Li, Li
AU  - Li L
FAU - Wu, Qian
AU  - Wu Q
FAU - Sun, Hong-Fen
AU  - Sun HF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Chemokines/analysis
MH  - Cytokines/analysis
MH  - Heparin, Low-Molecular-Weight/*therapeutic use
MH  - Male
MH  - Oxygen/blood
MH  - Pulmonary Artery/*drug effects/pathology
MH  - Pulmonary Embolism/*drug therapy/immunology
MH  - Rabbits
MH  - Urokinase-Type Plasminogen Activator/*therapeutic use
EDAT- 2013/06/22 06:00
MHDA- 2014/05/03 06:00
CRDT- 2013/06/22 06:00
PHST- 2013/06/22 06:00 [entrez]
PHST- 2013/06/22 06:00 [pubmed]
PHST- 2014/05/03 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2013 Jun;126(12):2254-9.