Mechanisms underlying increased reactivity of pulmonary arteries contralateral to a localized high-flow anastomosis. J Thorac Cardiovasc Surg 2011 Feb;141(2):425-31
Date
11/16/2010Pubmed ID
21075383Pubmed Central ID
PMC3052931DOI
10.1016/j.jtcvs.2010.07.007Scopus ID
2-s2.0-78751601116 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
OBJECTIVES: Our model of a systemic-pulmonary shunt exhibits enhanced reactivity of pulmonary arteries contralateral to a localized shunt between the left lower lobe pulmonary artery and aorta relative to those of ipsilateral or control pulmonary arteries 48 hours after anastomosis. We examined the contribution of nitric oxide, cyclooxygenase, lipoxygenase, or cytochrome P450 production to mediating this enhanced reactivity.
METHODS: We created a surgical end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta. Forty-eight hours later, we tested tension of pulmonary artery rings from the right and left lower lobes for contraction to the thromboxane mimetic U46619 in the presence of vehicle or inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450, or lipoxygenase. Western blots of pulmonary artery homogenates were probed for endothelial nitric oxide synthase or isoforms metabolizing arachidonic acid. Eicosanoid products from intact pulmonary artery rings were detected using labeled arachidonic acid and high-performance liquid chromatography separation.
RESULTS: Enhanced reactivity of unshunted right pulmonary arteries over that of left pulmonary arteries from high-flow hosts was not eliminated by inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450. Treatment with 2 different lipoxygenase inhibitors, nordihydroguaiaretic acid and cinnamyl-3,4-dihydroxy-α-cyanocinnamate, closed the difference in contractility of shunted and unshunted pulmonary arteries. Pulmonary arteries contralateral to shunts metabolized arachidonic acid to 12-hydroxyeicosatetraenoic acid in greater quantities than analogous pulmonary arteries from the experimental left or control pulmonary arteries.
CONCLUSIONS: Forty-eight hours after anastomosis, enhanced reactivity of contralateral pulmonary arteries is attributable in part to increased lipoxygenase products as opposed to nitric oxide or other eicosanoid products.
Author List
Pfister S, Somberg L, Lowry T, Gao Y, Medhora M, Jacobs ERAuthor
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anastomosis, SurgicalAnimals
Aorta
Arachidonic Acid
Blotting, Western
Chromatography, High Pressure Liquid
Cyclooxygenase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Dose-Response Relationship, Drug
Enzyme Inhibitors
Lipoxygenase
Lipoxygenase Inhibitors
Lung
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases
Pulmonary Artery
Pulmonary Circulation
Regional Blood Flow
Swine
Time Factors
Vascular Resistance
Vasoconstriction
Vasoconstrictor Agents
