PMID- 16616240
OWN - NLM
STAT- MEDLINE
DCOM- 20060517
LR  - 20161128
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 43
IP  - 4
DP  - 2006 Apr
TI  - Experimental pulmonary embolism: effects of the thrombus and attenuation of 
      pulmonary artery injury by low-molecular-weight heparin.
PG  - 800-8
AB  - BACKGROUND: Pulmonary embolism (PE) is a life-threatening condition that is 
      associated with the long-term sequelae of chronic pulmonary hypertension. Prior 
      experimental work has suggested that post-PE inflammation is accompanied by 
      pulmonary artery intimal hyperplasia. This study evaluated the effect of the 
      thrombus and tested the hypothesis that thrombolytic, antiplatelet, and 
      anticoagulant agents would decrease pulmonary injury. METHODS: Male 
      Sprague-Dawley rats (n = 267) underwent laparotomy and temporary clip occlusion 
      of the infrarenal inferior vena cava for the formation of endogenous thrombus or 
      placement of an inert silicone "thrombus." Two days later, repeat laparotomy was 
      performed, the clip removed, and the thrombus or silicone plug was embolized to 
      the lungs. The endogenous thrombus group received normal saline, 
      low-molecular-weight heparin (LMWH), tissue plasminogen activator (tPA), or a 
      gIIB/IIIA antagonist (abciximab). Lung tissue was harvested at various times over 
      21 days and assayed for total collagen, monocyte chemoattractant protein-1 
      (MCP-1), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-beta). 
      Fixed sections were stained with trichrome for intimal hyperplasia determination 
      and ED-1 monocytes and alpha-actin-positive staining. RESULTS: The overall 
      survival for rats undergoing PE was 90%, was not affected by treatment, and 84% 
      of all PE localized to the right pulmonary artery. The PE significantly reduced 
      Pa(O2) in all groups. Compared with controls, the silicone emboli group had an 
      increased level of IL-13 on day 1, an increased level of MCP-1 on day 4, and an 
      increase in the levels of all inflammatory mediators on day 14 (P < .05). 
      Accompanying these differences were greater pulmonary artery intimal hyperplasia 
      at days 4 and 21 in the silicone group compared with controls (P < .05). LMWH 
      treatment in the thrombus of PE rats significantly decreased IL-13 levels at all 
      time points, whereas treatment with abciximab or tPA significantly increased 
      IL-13 levels compared with controls. TGF-beta levels were significantly increased 
      by LMWH at day 4 and 14, and abciximab was associated with lower TGF-beta at day 
      14. Only LMWH was associated with less pulmonary artery intimal hyperplasia at 
      day 14 compared with controls and the other treatment groups. CONCLUSIONS: 
      Persistent pulmonary artery distention by an inert material is sufficient to 
      invoke significant inflammation and intimal hyperplasia independent of the 
      thrombus itself. Compared with nontreated PE, LMWH is the only therapy associated 
      with a significant reduction in late intimal hyperplasia and, with the exception 
      of TGF-beta, lower profibrotic growth-factor production.
FAU - Rectenwald, John E
AU  - Rectenwald JE
AD  - Department of Surgery, Jobst Vascular Research Laboratory, Section of Vascular 
      Surgery, University of Michigan, Ann Arbor, USA. jrectenw@umich.edu
FAU - Deatrick, K Barry
AU  - Deatrick KB
FAU - Sukheepod, Pasu
AU  - Sukheepod P
FAU - Lynch, Erin M
AU  - Lynch EM
FAU - Moore, Andrea J
AU  - Moore AJ
FAU - Moaveni, Daria M
AU  - Moaveni DM
FAU - Dewyer, Nicholas A
AU  - Dewyer NA
FAU - Luke, Catherine E
AU  - Luke CE
FAU - Upchurch, Gilbert R Jr
AU  - Upchurch GR Jr
FAU - Wakefield, Thomas W
AU  - Wakefield TW
FAU - Kunkel, Steven L
AU  - Kunkel SL
FAU - Henke, Peter K
AU  - Henke PK
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Anticoagulants)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
EIN - J Vasc Surg. 2006 Oct;44(4):914. Deywer, Nicholas A [corrected to Dewyer, 
      Nicholas A]
MH  - Angiography
MH  - Animals
MH  - Anticoagulants/*administration & dosage
MH  - Biopsy, Needle
MH  - Chemokines/analysis/metabolism
MH  - Cytokines/analysis/metabolism
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/drug effects/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Immunohistochemistry
MH  - Male
MH  - Probability
MH  - Pulmonary Artery/*pathology
MH  - Pulmonary Embolism/diagnostic imaging/*drug therapy/mortality/*pathology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reference Values
MH  - Risk Assessment
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Statistics, Nonparametric
MH  - Survival Rate
EDAT- 2006/04/18 09:00
MHDA- 2006/05/18 09:00
CRDT- 2006/04/18 09:00
PHST- 2005/10/05 00:00 [received]
PHST- 2005/12/03 00:00 [accepted]
PHST- 2006/04/18 09:00 [pubmed]
PHST- 2006/05/18 09:00 [medline]
PHST- 2006/04/18 09:00 [entrez]
AID - S0741-5214(05)02092-6 [pii]
AID - 10.1016/j.jvs.2005.12.010 [doi]
PST - ppublish
SO  - J Vasc Surg. 2006 Apr;43(4):800-8. doi: 10.1016/j.jvs.2005.12.010.