Gnecchi-Ruscone T, Montano N, Contini M, Guazzi M, Lombardi F, Malliani A
Servizio di Cardiologia, Ospedale di Merate (Co), Merate, Italy.
J Auton Nerv Syst. 1995 Jun 25;53(2-3):175-84. doi: 10.1016/0165-1838(94)00169-k.
Adenosine is a possible mediator of cardiac pain during myocardial ischemia; however, little is known about the influence of adenosine on cardiac sympathetic afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized, decerebrated, curarized and artificially ventilated cats, we studied the impulse activity of 20 single afferent sympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions and arterial pressure rises. All fibers increased their impulse activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold receptor characteristics. In 10 cats, epicardial applications of three different doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abolished by aminophylline, a P1 purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively, after the end of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the second occlusion initiated 30 s after the end of adenosine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by adenosine. This effect was no longer present during the last occlusion performed after 7 min. When the protocol was repeated substituting adenosine with saline (n = 5) or after i.v. administration of aminophylline (n = 5), no potentiation was observed, even though the excitatory response to coronary occlusion was preserved. These data show that adenosine can activate cardiac sympathetic afferent fibers in a dose-related manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The excitatory effects are likely to involve the P1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an algogenic code.
腺苷可能是心肌缺血时心脏疼痛的介质；然而，关于腺苷对心脏交感神经传入活动的影响及其致痛机制，人们知之甚少。在20只麻醉、去大脑、箭毒化并人工通气的猫中，我们研究了20条在左心室有感受野的单根传入交感神经纤维的冲动活动，这些活动与心外膜应用腺苷、冠状动脉闭塞及动脉压升高的关系。在主动脉压轻度升高（20±8%）时，所有纤维的冲动活动均增加（从1.2±0.2次/秒增至2.6±0.5次/秒；P<0.001），从而表现出低阈值感受器特性。在10只猫中，心外膜应用三种不同剂量的腺苷（0.1、1和10毫克/毫升）导致神经活动短暂增加，且呈剂量相关反应。该反应可被P1嘌呤能抑制剂氨茶碱消除。在另一组10只猫中，对供应纤维感受野的冠状动脉血管进行了四次连续30秒的闭塞，分别在对照条件下以及在应用腺苷（1毫克/毫升）诱导兴奋结束后30秒、3分钟和7分钟时进行。在对照冠状动脉闭塞期间，冲动活动从1.1±0.1次/秒增至5.5±0.7次/秒（P<0.0001）。在腺苷诱导的激活结束后30秒开始的第二次闭塞期间，出现了类似的激活。相比之下，在腺苷兴奋结束后3分钟开始的闭塞期间，观察到反应有显著增强（8.8±1.2次/秒对5.3±0.9次/秒；P<0.001）。在7分钟后进行的最后一次闭塞期间，这种效应不再存在。当用生理盐水替代腺苷（n=5）或静脉注射氨茶碱（n=5）后重复该方案时，即使对冠状动脉闭塞的兴奋反应得以保留，也未观察到增强作用。这些数据表明，腺苷能以剂量相关的方式激活心脏交感神经传入纤维，并增强它们对冠状动脉闭塞的反应，同时不影响对血流动力学刺激的反应性。兴奋作用可能涉及P1嘌呤能受体。增强现象可能在致痛编码的发生中起作用。
