Pharmacological study of purinergic mechanism for cardiac sinus node pacemaker activity

在抗凝剂麻醉下分离犬心脏后，制备含窦房结区的右心房标本。用麻醉的供体犬肝素化血液，以100 mmHg恒压灌流离体心房的窦房结动脉，连续输注腺苷引起负性变时性和变力性效应，收缩力逐渐恢复到对照水平，但起搏活动不在输注范围内。1.起搏器活动和收缩性对腺苷的反应是不同的。反应呈剂量依赖性。2.腺苷输注抑制腺苷的推注给药，显示急性脱敏现象。然而，他们没有抑制乙酰胆碱诱导的反应，而是加强。3.腺苷输注轻微但显著抑制去甲肾上腺素诱导的正性变时和变力作用。4.心内神经电刺激引起的负性和正性双相变时性和变力性反应，使心脏负性反应增强，而正性反应减弱。腺苷、乙酰胆碱、去甲肾上腺素诱导的心脏效应。今后，有必要对腺苷的病理生理和药理学问题进行深入研究。

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.