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.
