Loeb J M, deTarnowsky J M, Aksamit T R
J Electrocardiol. 1985 Jul;18(3):287-94. doi: 10.1016/s0022-0736(85)80053-4.
Recent evidence supports a complex relationship between pressure in the sinus node artery and heart rate. In addition, it has been suggested that acetylcholine effects vary depending upon the pressure at which the drug is injected. We examined the cardiac chronotropic responses to acetylcholine, delivered via the sinus node artery using a constant flow perfusion technique. Dogs were anesthetized with chloralose and prepared to record ECG, arterial pressure and bipolar electrograms from the sinus node, sulcus terminalis, right atrium, right ventricle and His bundle. The sinus node artery was catheterized, distribution verified and autologously perfused via the femoral artery. Both vagi and both stellate ganglia were transected. Analog data were processed by computer for each cycle length during perfusion with normal Tyrode solution or Tyrode solution containing acetylcholine. Perfusion of normal Tyrode solution (1-4ml/min) resulted in prolongation in cycle length which was greater at higher flow rates but rapidly dissipated at all flow rates. Beyond mechanically-induced bradycardia, acetylcholine initially prolonged cycle length but cycle length prolongation faded with time. Delivery of acetylcholine at higher flow rates resulted in significantly greater prolongation of cycle length. Cycle length always returned back toward control although perfusion of acetylcholine continued. Thus, responses to acetylcholine are influenced not only by drug concentration but also by the flow rate at which the drug is delivered. This suggests a coupling of mechanical and pharmacologic components of chronotropic influences at the sinus node.
最近的证据支持窦房结动脉压力与心率之间存在复杂关系。此外，有人提出乙酰胆碱的作用因药物注射时的压力而异。我们使用恒流灌注技术，通过窦房结动脉给药，研究了心脏对乙酰胆碱的变时反应。用氯醛糖麻醉犬，并准备记录心电图、动脉压以及来自窦房结、终沟、右心房、右心室和希氏束的双极电图。将导管插入窦房结动脉，确认其分布，并通过股动脉进行自体灌注。切断双侧迷走神经和双侧星状神经节。在用正常台氏液或含乙酰胆碱的台氏液灌注期间，计算机对每个心动周期长度的模拟数据进行处理。灌注正常台氏液（1 - 4毫升/分钟）导致心动周期长度延长，在较高流速时延长更明显，但在所有流速下均迅速消散。除了机械性诱发的心动过缓外，乙酰胆碱最初使心动周期长度延长，但随着时间推移，心动周期长度延长逐渐消失。以较高流速给予乙酰胆碱导致心动周期长度延长显著增加。尽管继续灌注乙酰胆碱，但心动周期长度总是恢复到对照水平。因此，对乙酰胆碱的反应不仅受药物浓度影响，还受药物给药流速影响。这表明窦房结变时影响的机械和药理成分之间存在耦合。
