The bronchial circulation perfuses an extensive microvascular plexus in the submucosa and adventitia of large airways and parenchymal bronchi. Inflammatory mediators, e.g. histamine, bradykinin, and substance P, alter the ultrastructure and selectively increase the permeability of bronchial venules while having relatively little effect on the pulmonary circulation. The vessels of the bronchial circulation exhibit greater vasodilation during inflammation than those of any other circulation. The highly reactive inflammatory changes in permeability and blood flow of bronchial vessels may be related to either the afferent nerve supply of airway mucosa and the initiation of a type of axon reflex or to the distribution of mast cells in the lung. The above observations suggest the following hypothesis: The development of pulmonary edema during inflammatory lung disease results in part from the highly reactive bronchial circulation. The overall goal of this project is to determine how increased blood flow and permeability of the bronchial circulation is regulated and how these alterations contribute to the development of pulmonary edema.
Specific aims are: 1) to continue to evaluate and improve methods for microsphere measurement of the intrapulmonary distribution of bronchial blood flow. Studies will be designed to compare measurements made with microspheres and doppler flow probes on the bronchial artery, and to quantitate shunting in the bronchial circulation: 2) to develop and evaluate an animal model to measure blood-to-tissue transport of albumin in central and peripheral airways and whole lung; 3) to compare the short and long term effects of occlusion of the sheep's main bronchial artery: to measure the collateral systemic input and any pulmonary blood flow to airway mucosa; to evaluate how bronchial artery occlusion affects lung lymph flow and the development of pulmonary edema: 4) to determine interactions between mast cell mediators and sensory afferent tachykinins on the control of blood flow and microvascular permeability of the bronical circulation; 5) to evaluate the effectiveness of various anti-inflammatory agents and local anesthetics on the hyperemia and permeability alterations of inflammation. A key part of our plan is to carefully evaluate the intrapulmonary distribution of blood flow and the changes in vascular permeability during inflammatory challenges. A better understanding of the control of blood flow and vascular permeability of the bronchial circulation may lead to new effective therapies for treatment of asthma and other inflammatory lung diseases.
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