2004 Fiscal Year Final Research Report Summary
Mechanisms responsible for alveolar fluid reabsorption during peri-operative period
| Project/Area Number |
14571287
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
SAKUMA Tsutomu Kanazawa Medical University, Thoracic Surgery, MD, PhD, Professor, 医学部, 教授 (90215674)
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| Co-Investigator(Kenkyū-buntansha) |
SAGAWA Motoyasu Kanazawa Medical University, Thoracic Surgery, Associate Professor, MD, PhD, 医学部, 助教授 (70292274)
ISHIGAKI Masanobu Kanazawa Medical University, Thoracic Surgery, Assistant Professor, MD, PhD, 医学部, 助手 (10247439)
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| Project Period (FY) |
2002 – 2004
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| Keywords | alveolar fluid clearance / perioperative / malnutrition / beta-adrenoceptor / prostaglandin / purinoceptor / CFTR / alveolar epithelium |
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| Research Abstract |
The objectives of this study were to determine whether malnutrition, selective β-adrenergic agonists, and purinoceptors had effects on alveolar fluid clearance in rat lungs, to determine whether catecholamine clearance from the alveolar spaces was correlated with the fluid transport capacity of the rat and human lungs, and to whether endogenous levels of catecholamine stimulated alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator (CFTR) in human lungs. We found that malnutrition impaired amiloride-insensitive and dibutyryl cGMP-sensitive alveolar fluid clearance, but this effect was partially reversible by re-feeding, treatment with sodium glutamate, or β-adrenergic agonist therapy. Prostaglandin analogues do not change basal alveolar fluid clearance and the effect of terbutaline at normal dose on alveolar fluid clearance, but restored the stimulatory effect as a β_1-adrenergic antagonist in ex vivo rat lungs with an administration of high-dose β_2-adrenergic antagonist. A combined treatment of UTP and isoproterenol increased alveolar fluid clearance by 280% basal value. The effects of UTP in the presence and absence of isoproterenol were abolished by blockers of a P2 purinoceptor and chloride channels. Catecholamine clearance rate from the alveolar spaces is correlated with alveolar fluid clearance in the rat and human lungs. Endogenous catecholamine concentrations in edema fluid were not sufficient to stimulate the resolution of acute pulmonary edema. Exogenous epinephrine, but not norepinephrine, stimulated alveolar fluid clearance via CFTR in ex vivo human lung. These studies indicate that alveolar fluid clearance play an important role in resolution of pulmonary edema of patients who underwent pulmonary resection. Beta-adrenergic agonist therapy may be considered in a patient exposed to pulmonary edema after pulmonary resection.
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