Heparin Accelerates Pulmonary Artery Development in Neonate Rabbits
SUGURU WATANABE,1,2 TAKASHI SUZUKI,1 SOUICHIROU SHIZAWA,1 MASATO ENDOH,2 KOUICHI TABAYASHI2 and HIRONOBU SASANO1
1Departments of Pathology, and Thoracic, and 2Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan
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.
keywords ——pulmonary artery vascular resistance; pulmonary vascular density; heparin; CD31; image analysis
© 2005 Tohoku University Medical Press
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Tohoku J. Exp. Med., 2005, 207, 171-179
Correspondence: Suguru Watanabe, M.D., Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.
e-mail: suguruw@mail.tains.tohoku.ac.jp