Document Detail

Low molecular weight heparin and unfractionated heparin are both effective at accelerating pulmonary vascular maturation in neonatal rabbits.
MedLine Citation:
PMID:  12970226     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Creation of a bi-directional cavopulmonary shunt after the Norwood procedure for hypoplastic left heart syndrome is delayed to allow pulmonary vascular resistance to fall with maturation of the pulmonary vascular bed. We hypothesized that unfractionated heparin (UFH) and low molecular weight heparin (LMWH), which promote angiogenesis and inhibit smooth muscle cell growth, could accelerate this process. METHODS AND RESULTS: Fifty-six newborn rabbits were randomly selected to receive UFH 225U/kg (n=12), LMWH 1 mg/kg (n=14), LMWH 10 mg/kg (n=16), or saline (n=14) by subcutaneous injection every 12 hours for 14 days. Treatment with heparin reduced mean pulmonary artery (PA) pressure by 12% to 16% relative to controls [9.0+/-0.2 (UFH), 9.4+/-0.1 (LMWH 1 mg/kg), 9.2+/-0.2 (LMWH 10 mg/kg) versus 10.7+/-0.2 mm Hg (saline), P=0.0001]. Lower PA pressures were associated with reduced alveolar:arterial ratio consistent with enhanced pulmonary angiogenesis in heparin treated animals [8+/-1 (UFH), 13+/-2 (LMWH 1 mg/kg), 12+/-2 (LMWH 10 mg/kg) versus 23+/-5 (saline), P<0.03]. Reduced PA medial wall thickness and muscularization, two additional features of pulmonary vascular maturation, were also more evident in heparin treated animals. Mean PA pressures in 14-day-old rabbits treated with heparin were lower than those measured in control rabbits less than 7 weeks of age suggesting that heparin shortens the pulmonary vascular maturation process by over 60%. CONCLUSIONS: These results indicate that both UFH and LMWH are effective at accelerating pulmonary vascular maturation in newborn rabbits. This raises the possibility that administration of heparin to children after the Norwood procedure might allow for earlier conversion to a bi-directional cavopulmonary shunt.
Stacy B O'Blenes; Sandra L Merklinger; Anusha Jegatheeswaran; Andrew Campbell; Marlene Rabinovitch; Ivan Rebeyka; Glen Van Arsdell
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Circulation     Volume:  108 Suppl 1     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-12     Completed Date:  2003-09-30     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  II161-6     Citation Subset:  AIM; IM    
Division of Cardiovascular Surgery, The Hospital for Sick Children and The University of Toronto, Toronto, Ontario, Canada.
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MeSH Terms
Animals, Newborn
Blood Pressure / drug effects
Fibroblast Growth Factor 2 / metabolism
Heart Ventricles / anatomy & histology,  drug effects
Heparin / pharmacology*
Heparin, Low-Molecular-Weight / pharmacology*
Lung / blood supply,  drug effects,  metabolism
Muscle, Smooth, Vascular / anatomy & histology,  drug effects
Neovascularization, Physiologic
Pulmonary Artery / anatomy & histology,  drug effects*,  growth & development,  physiology
Reg. No./Substance:
0/Heparin, Low-Molecular-Weight; 103107-01-3/Fibroblast Growth Factor 2; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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