Heparin Accelerates Pulmonary Artery Development in Neonate Rabbits

Abstract

Pulmonary vascular resistance drops sharply within a few minutes after birth for the survival of neonates. A majority of this resistance is caused by "pulmonary vascular bed" or vessel lacking smooth muscle cells. Heparin is known to promote proliferation and development of endothelial cells and to subsequently decrease their overall vascular resistance, but its detailed features remained unknown. Therefore, in this study we treated neonatal rabbits with heparin, protamine (antagonist of heparin), or saline, and evaluated histopathological features of vascular endothelial cells using two different types of computer assisted image analysis, i.e., CAS200 and NIH image. These two systems detected the percentage of vascular endothelial area per fields (VA) and CD31-positive area per total area of tissue following subtraction of background stain. CD31 was used as an endothelial cell marker. Heparin treated rabbits were associated with significant decrement of pulmonary/systemic artery pressure (Pp/Ps) (21.0 ± 6.0%) compared to protamine (29.9 ± 6.1%) or saline (29.4 ± 3.0%) treated animals. The values of VA obtained by the two image analyses (CAS200 and NIH image) were significantly increased in heparin treated animals (38.4 ± 3.2% determined by CAS200 and 24.0 ± 1.3% by NIH image) compared to protamine (30.2 ± 3.9% and 19.2 ± 1.8%) or saline (33.2 ± 1.5% and 20.8 ± 3.8%) treated animals on 14th day of treatment. The present study indicates that heparin accelerates pulmonary vascular bed development probably by increasing the number and volume of endothelial cells, which subsequently contributes to the decrease in pulmonary vascular resistance. pulmonary artery vascular resistance; pulmonary vascular density; heparin; CD31; image analysis

Intrapleural heparin or heparin combined with human recombinant DNase is not effective in the treatment of empyema in a rabbit model

“…route. 26 This study showed that the intrapleural administration of 1000 IU heparin alone or in combination with 1 mg of rhDNase did not facilitate the treatment of empyema in rabbits. Intrapleural heparin significantly increased the drainage of pleural fluid compared with combination and saline groups.…”

“…In the rabbit model of thromboemboli, heparin dose usually varies between 125 and 500 UI/kg/day for i.v. route 26 …”

The Effects of Antenatal Anticoagulants (Low-Molecular-Weight Heparin and Aspirin) on Neonatal Pulmonary Vasculature in Rabbits

“…The most prominent structural change in the pulmonary vascular bed of newborn rabbits was found to be reduction in the alveolar:arteriolar ratio associated with new vessel growth, but the mechanism could not be understood. In another study [31], it was shown that UFH accelerates pulmonary artery development and decreases pulmonary artery pressure in neonatal rabbits. This fact was explained by the effect of heparin promoting pulmonary vascular proliferation and nitric oxide synthesis.…”