This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by O’Blenes, S. B. Articles by Van Arsdell, G. Search for Related Content PubMed PubMed Citation Articles by O’Blenes, S. B. Articles by Van Arsdell, G.

(Circulation. 2003;108:II-161.)
© 2003 American Heart Association, Inc.

Surgery for Congenital Heart Disease

Low Molecular Weight Heparin and Unfractionated Heparin Are Both Effective at Accelerating Pulmonary Vascular Maturation in Neonatal Rabbits

Stacy B. O’Blenes, MD, MSc; Sandra L. Merklinger, MN; Anusha Jegatheeswaran, BSc; Andrew Campbell, MD, PhD; Marlene Rabinovitch, MD; Ivan Rebeyka, MD; Glen Van Arsdell, MD

From the Division of Cardiovascular Surgery, The Hospital for Sick Children and The University of Toronto, Toronto, Ontario, Canada; Division of Cardiovascular Research, The Hospital for Sick Children and The University of Toronto, Toronto, Ontario, Canada; The University of Alberta, Edmonton, Alberta, Canada.

Correspondence to Glen Van Arsdell, MD, Cardiovascular Surgery, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8. Phone: 416-813-6420, Fax: 416-813-7984, E-mail: glen.vanarsdell{at}sickkids.ca

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.

Key Words: pulmonary artery • angiogenesis • anticoagulants • growth factors • heart defects • congenital