ARRHYTHMIA FORMATION DURING DIGOXIN-QUINIDINE THERAPY

同时接受地高辛和奎尼丁的患者注意到， 血浆地高辛浓度显著增加。 的 这些患者易发生毒性的程度 地高辛的症状存在争议。 但由于 心律不齐形成是这种情况的潜在严重并发症 药物治疗，这个问题应该得到解决。 的目的 这项研究是为了确定是否有增加， 发病率或易感性，以确定是否有增加 无论是发病率还是易感性， 地高辛-奎尼丁给药期间的心律失常，并揭示 可能的电生理机制。 在 第一系列的实验，8只狗， 植入3对心脏电极，将接受地高辛 0.0125毫克/ kg/天，持续12天，随后为地高辛+奎尼丁 15 mg/kg，每日两次，持续5天。 接下来，狗狗们将被分 分为两组，分别接受奎尼丁或（d）地高辛， 正常剂量的两倍，持续7天。 每次给药后， 将监测ECG变化2小时。 然后他们会 麻醉并检测房室结传导的变化 以及心室兴奋性的变化 述第二触发器串列中 实验中，左前降支冠状动脉将 在20只麻醉的狗中结扎。 狗会康复的， 接受地高辛或地高辛加奎尼丁。 6号之后 第二天，将犬麻醉，并进行程控心脏起搏， 起搏以测试心律失常敏感性。 在第三个系列中， 实验中，使用来自动物心脏的浦肯野纤维切片 将在Tyrodes溶液中灌注。 地高辛灌注期间的微电极检查将 确定诱导后电位所需的时间和/或 心搏停止 研究结果应揭示（a）心律失常是否 是地高辛-奎尼丁同时给药期间的潜在问题 治疗，（B）如果在奎尼丁存在下血清地高辛水平 反映地高辛的治疗和毒性潜力，（c）如果 奎尼丁和地高辛的作用是相加的。 此类信息 对于治疗患有 这些药物或其他提高地高辛水平的药物。

Patients receiving digoxin and quinidine concurrently are noted to have a significant increase in plasma digoxin concentrations. The extent to which these patients are susceptible to develop toxicity symptoms of digoxin is controversial. However, because arrhythmia formation is a potentially serious complication of this drug therapy, this problem should be addressed. The purpose of this study is to determine if there is an increase in either the incidence or the susceptibility to determine if there is an increase in either the incidence or the susceptibility to develop arrhythmias during digoxin-quinidine administration, and to reveal possible electrophysiologic mechanisms for arrhythmogenesis. In the first series of experiments, 8 dogs that were previously implanted with 3 pair of cardiac electrodes, will receive digoxin 0.0125 mg./kg/day for 12 days followed by digoxin plus quinidine 15 mg/kg twice daily for 5 days. Next, the dogs will be divided into two groups and receive either quinidine or (d) digoxin at twice the normal dose for 7 days. After each regimen, the dogs will be monitored for 2 hours for changes in ECG. Then they will be anesthetized and tested for changes in AV nodal conduction and changes in ventricular excitability. In the second series of experiments, the Left Anterior Descending Coronary Artery will be ligated in 20 anesthetized dogs. The dogs will recover and receive either digoxin or digoxin plus quinidine. After the 6th day, dogs will be anesthetized, and undergo programmed cardiac pacing to test for arrhythmia susceptibility. In the third series of experiments, Purkinje fiber sections from hearts of animals used in the above studies will be perfused in Tyrodes solution. Microelectrode examination during perfusion with digoxin will determine the time necessary to induce afterpotentials and/or asystole. The results of the study should reveal (a) if arrhythmias are a potential problem during concurrent digoxin-quinidine therapy, (b) if serum digoxin levels in the presence of quinidine reflect the therapeutic and toxic potential of digoxin, (c) if the actions of quinidine and digoxin are additive. Such information would be valuable to clinicians who are treating patients with these drugs or other drugs that raise digoxin levels.