Early Stages in the Development of Collateral Circulation to the Lung in the Rat

The early stages of the development of collateral circulation to the lung following experimental ligation of the pulmonary artery were studied in adult rats. Five different types of vessels were found to be involved: 1. The bronchial arteries enlarge. Quantitative gross and microscopic studies indicated that this is first due to hemodynamic factors leading to dilatation of the vessels. After 5 days, true growth of the vessels occurs, associated with proliferative changes in the vessel wall, including mitoses in endothelial and smooth muscle cells. 2. Pre-existing nutrient arteries of the heart muscle coat of the pulmonary veins enlarge by the same processes. 3. New vessels form in the granulation tissue at the ligature. They can grow through the thick vessel wall into the lumen of the main pulmonary artery to form a considerable portal of entry for blood into this vessel. 4. Vessels form in pleural adhesions and can supply blood to the lung from intercostal arteries. 5. New bronchial arteries form in regions where no granulation tissue formation could stimulate their development. The primary anlage consists of a solid cell cord, soon surrounded by an envelope of spindle-shaped cells, representing the anlage of the media. The cell cord differentiates secondarily to an endothelial tube by forming a lumen. The enlarged systemic arteries are directly connected to the lung capillaries by means of multiple small branches, which are also newly formed arteries or arterioles. Arterial bronchopulmouary anastomoses are not as commonly found early in the development of collateral circulation in the rat, as late in this process in dogs. It may be concluded that the enlargement of collateral arteries to the lung following ligation of the pulmonary artery may be initiated by hemodynamic conditions, such as changed pressure gradients. After 5 days, however, other, probably humoral, factors must be responsible for further stimulation of the growth of pre-existing vessels and for the initiation and guidance of new vessel formation.