A study of mechanism in atrial fibrillation

心房颤动的机制研究

• 批准号: 62570388
• 负责人: ITO Takayuki
• 金额: $ 1.28万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570388/
• 关键词: Atrial Fibrillation; c-GMP; ANP; Atrial Fibrillation Threshold; Atrial Pacing; Atrial Stretch; cーGMP; 心房ペーシング; 冠動脈; C-GMP

To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP) on AFT were determined. Plasma levels of c-GMP, c-AMP and atrial natriuretic peptide (ANP) were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. Dbc-GMP induced a dose- dependent decrease in AFT. Clinical assessment revealed that patients had almost four times higher c-GMP and ANP levels during AF than during sinus rhythm. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.Plasma concentrations of ANP and c-GMP were significantly … More correlated with mean pulmonary arterial pressure and right atrial diameter in 89 patients with heart disease. It is suggested that increased plasma concentrations of ANP were induced by increased atrial pressure as well as atrial distention in human.hANP relaxed canine coronary artery, and that increased tissue c-GMP levels in a dose-dependent fashion. The results suggest that hNAP relaxes the coronary artery by directly activating the guanylate cyclase in coronary smooth muscle.The role of intracellular signals in the regulation of ANP release was investigated using isolated rat left atria. Dibutyryl cyclic AMP and dibutyryl cyclic GMP had no effect on ANP release. Arginine vasopressin and phenylephrine stimulated ANP release dose-dependently. The ANP release stimulated by phenylephrine was inhibited by W-7, a calmodulin antagonist, and H-7, a protein kinase C inhibitor. Atrial stretch stimulated ANP release, but the release was not inhibited by W-7 or H-7. These results suggest that the mechanism responsible for stretch-induced ANP release differs from that for phenylephrine-induced ANP release. Less

为了研究环状核苷酸在发生性纤颤（AF）（AF）的持续性中的作用，在具有电诱导的AF的狗中测量了环状GMP（C-GMP）的血浆水平（C-GMP）和环状AMP（C-AMP）。确定了AFT上C-GMP（DBC-GMP）静脉内给药后的心房颤动阈值（AFT）。在阵发性AF和窦性节奏期间，还测量了患者的C-GMP，C-AMP和心房纳地肽（ANP）的血浆水平。人工AF发作后15分钟，C-GMP水平显着升高，并在实验过程中逐渐增加。 DBC-GMP诱导AFT的剂量依赖性降低。临床评估表明，在AF期间，患者的C-GMP和ANP水平几乎是窦性心律时期的四倍。这些结果表明，C-GMP的增加在AF的维持和/或起源中起着重要作用。在89例心脏病患者中，ANP和C-GMP的血压浓度与平均肺动脉压和右心房直径显着相关。据建议，人类心理压力增加以及人心房距离诱导了血浆浓度的增加。结果表明，HNAP通过直接激活冠状动脉平滑肌中的鸟苷酸环化酶来放松冠状动脉。使用分离的大鼠左心房研究了细胞内信号在调节ANP释放中的作用。二苯乙烯循环AMP和双苯乙烯环状GMP对ANP释放没有影响。精氨酸加压素和苯肾上腺素刺激了ANP释放剂量依赖性。由苯基抑制蛋白拮抗剂W-7和蛋白激酶C抑制剂H-7抑制了由苯细胞刺激的ANP释放。心房拉伸刺激了ANP的释放，但是W-7或H-7并未抑制释放。这些结果表明，导致拉伸诱导的ANP释放的机制与苯菌PRN诱导的ANP释放的机制不同。较少的

项目成果

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