Our long-term objective is the treatment of cardiac arrhythmia in the ambulatory patient by automatic infusion of antiarrhythmic drugs from an implanted pump. The system would operate """"""""closed-loop"""""""" by following a cyclic sequence of tachycardia detection, drug delivery, tachycardia re-evaluation, and readjustment of drug delivery. The present proposal describes the three basic studies which must be completed before such an implantable system can be designed for clinical trial. These are 1. Arrhythmia Detection, 2. Pharmacokinetically Based Infusion, and 3. Implant Testing. Thus our specific aim in this proposal is to demonstrate the following hypotheses: 1. Arrhythmia Detection. Automatic arrhythmia detection using a new technique designed by us for an anti-tachycardia pacemaker is sufficiently reliable to be used to initiate and regulate drug infusion. 2. Pharmacokinetically Based Infusion. Computerized infusion based on patient-specific, adaptive and continuous pharmacokinetic evaluation provides faster and more precise control of plasma levels than conventional therapy. 3. Implant Testing. Implantation of the arrhythmia detector and infusion pump is technically feasible. These hypotheses will be tested in dogs in which catheters are in place for intracardiac recording, intravenous infusion, and blood sampling and in which paroxysmal tachyarrhythmia can be provoked at will. We will test the ability of the system to detect the arrhythmia and automatically deliver an antiarrhythmic drug in a closed-loop manner in the laboratory, using a microcomputer-based intravenous pump. Then a miniaturized version will be implanted and tested in awake and ambulatory animals. In addition to these animal experiments, we propose to test 1) and 2) in patients with recurrent tachyarrhythmias who are undergoing drug testing in the electrophysiology laboratory. Since externalized catheters are already in place, tachyarrhythmias can be induced and detected and then treated with antiarrhythmic drugs under cardiologist control in a semi-automatic, pseudo closed-loop protocol. A successful result for these tests will permit the design of a future study in which the system will be implanted in selected patients refractory to oral drug therapy and/or antitachycardia pacing.
