Pharmacological study of purinergic mechanism for cardiac sinus node pacemaker activity

心脏窦房结起搏器活性的嘌呤能机制的药理学研究

• 批准号: 13670082
• 负责人: CHIBA Shigetoshi
• 金额: $ 1.98万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670082/
• 关键词: Isolated canine right atria; Sinus node artery; Blood-perfused sinus node preparation; Adenosine; Desensitization; Intracardiac nerve stimulation; イヌ洞結節動脈; ノルアドレナリン; アセチルコリン; 心臓内自律神経刺激

After the canine heart was isolated under anesthesia with anticoagulant treatment, the right at rial preparation containing the sinus node area was prepared. With the anesthetized donor dog's heparinized blood, the sinus node artery of the isolated atrium was perfused at the 100 mmHg of constant pressure.A continuous infusion of adenosine caused negative chrono- and inotropic effects, and the contractility gradually returned to the control level but the pacemaker activity did not within the infusion. 1. Responses of pacemaker activity and contractility to adenosine are differentiated. The responses were dose-dependent. 2. The adenosine infusion inhibited a bolus administration of adenosine, showing the acute desensitization phenomenon. However, they did not inhibit the acetylcholine-induced response but rather potentiated that. 3. The adenosine infusion slightly but significantly inhibited the norepinephrine-induced positive chrono-and inotropic effects. 4. The biphasic negative and positive chrono- and inotropic responses to intracardiac nerve electric stimulation caused to enhance the negative cardiac but to depress the positive responses.In the present experiments, it was confirmed that adenosine influences physiological control factors, i.e., adenosine-, acethylcholine-, norepinephrine-induced cardiac effects. In the future, it is necessary to investigate the pathophysiological and pharmacological problems for adenosine.

在麻醉和抗凝治疗下分离犬心脏后，制备含有窦房结区域的右心房标本。用麻醉供体犬的肝素化血液，在100 mm Hg恒压下灌流离体心房窦房结动脉，持续输注腺苷产生负性变时和变力作用，收缩功能逐渐恢复到对照水平，但起搏活动不在灌流范围内。1.起搏器活动和收缩能力对腺苷的反应是不同的。这些反应是剂量依赖性的。2.腺苷注射抑制腺苷的一次给药，出现急性脱敏现象。然而，它们并没有抑制乙酰胆碱诱导的反应，反而增强了这种反应。3.腺苷输注对去甲肾上腺素的正性变时和变力作用有轻微的抑制作用，但有显著的抑制作用。4.心内神经电刺激引起的负性和正性变时性和变力性双相反应，使负性心脏反应增强，但抑制正性反应。今后有必要对腺苷的病理生理和药理问题进行深入的研究。

项目成果

Chiba, Shigetoshi: "Dominant anti-vagal effect of pentobarbital on cardiac responses to intracardiac autonomic nerve stimulation in the dog"Japanese Journal of Pharmacology. 86巻4号. 248-250 (2001)

Chiba, Shigetoshi：“戊巴比妥对狗心内自主神经刺激的心脏反应的显着抗迷走神经作用”，《日本药理学杂志》，第 86 卷，第 4 期。248-250（2001 年）。

Kurogouchi, Fumio: "Heterogenous distribution of β-adrenoceptors and muscarinic receptors in the sinoatrial node and right atrium of the dog"Clinical and Experimental Pharmacology and Physiology. 29巻8号. 666-672 (2002)

Kurogouchi，Fumio：“狗窦房结和右心房中 β-肾上腺素受体和毒蕈碱受体的异质分布”，临床和实验药理学和生理学，第 29 卷，第 8 期。666-672 (2002)。

Shigetoshi Chiba, et al.: "Dominant anti-vagal effect of pentobarbital on cardiac responses to intracardiac nerve stimulation in the dog."Japanese Journal of Pharmacology. 84(4). 248-250 (2001)

Shigetoshi Chiba 等人：“戊巴比妥对狗心脏对心内神经刺激的反应具有显着的抗迷走神经作用。”日本药理学杂志。

Tsuboi, Masato: "Adenosine infusion inhibits adenosine-induced cardiac actions but enhances acetylcholine-induced actions in isolated dog atria"Heart Vessels. 18巻. (2003)

Tsuboi，Masato：“腺苷输注可抑制腺苷诱导的心脏作用，但增强离体狗心房中乙酰胆碱诱导的作用”《心脏血管》第 18 卷。（2003 年）

Tsuboi, Masato: "Adenosine infusion inhibits adenosine-induce actions but enhances acetylcholine-induced actions in isolated dog atria"Heart Vessels. 18巻(印刷中). (2003)

Tsuboi，Masato：“腺苷输注可抑制腺苷诱导作用，但增强离体狗心房中乙酰胆碱诱导的作用”《心脏血管》第 18 卷（出版中）。