Pharmacological study of purinergic mechanism for cardiac sinus node pacemaker activity

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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.