PMID- 12970226
OWN - NLM
STAT- MEDLINE
DCOM- 20030930
LR  - 20031114
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 108 Suppl 1
DP  - 2003 Sep 9
TI  - Low molecular weight heparin and unfractionated heparin are both effective at 
      accelerating pulmonary vascular maturation in neonatal rabbits.
PG  - II161-6
AB  - 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.
FAU - O'Blenes, Stacy B
AU  - O'Blenes SB
AD  - Division of Cardiovascular Surgery, The Hospital for Sick Children and The 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Merklinger, Sandra L
AU  - Merklinger SL
FAU - Jegatheeswaran, Anusha
AU  - Jegatheeswaran A
FAU - Campbell, Andrew
AU  - Campbell A
FAU - Rabinovitch, Marlene
AU  - Rabinovitch M
FAU - Rebeyka, Ivan
AU  - Rebeyka I
FAU - Van Arsdell, Glen
AU  - Van Arsdell G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Blood Pressure/drug effects
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Heart Ventricles/anatomy & histology/drug effects
MH  - Heparin/*pharmacology
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Kinetics
MH  - Lung/blood supply/drug effects/metabolism
MH  - Muscle, Smooth, Vascular/anatomy & histology/drug effects
MH  - Neovascularization, Physiologic
MH  - Pulmonary Artery/anatomy & histology/*drug effects/growth & 
      development/physiology
MH  - Rabbits
EDAT- 2003/09/13 05:00
MHDA- 2003/10/01 05:00
CRDT- 2003/09/13 05:00
PHST- 2003/09/13 05:00 [pubmed]
PHST- 2003/10/01 05:00 [medline]
PHST- 2003/09/13 05:00 [entrez]
AID - 108/10_suppl_1/II-161 [pii]
AID - 10.1161/01.cir.0000087380.36688.4c [doi]
PST - ppublish
SO  - Circulation. 2003 Sep 9;108 Suppl 1:II161-6. doi: 
      10.1161/01.cir.0000087380.36688.4c.