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

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Abstract
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 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.