Efficacy of Epicardial Controlled-Release Lidocaine for Ventricular Tachycardia Induced by Rapid Ventricular Pacing in Dogs

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Abstract
The effects of epicardial lidocaine on ventricular tachycardia (VT) induced by rapid ventricular pacing (50 Hz) were studied in dogs. Lidocaine-polyurethane (28% wt/wt) matrixes (40-50 mg, 5 .times. 5 mm) were placed proximal to bipolar left ventricular epicardial electrodes in open-chest anesthetized dogs (n = 9) after VT was established by rapid ventricular pacing. In the first set of experiments, matrices were removed immediately after VT had converted to sinus rhythm. Control animals underwent VT induction protocol with a nondrug-containing matrix positioned next to the epicardial electrode. In the lidocaine-treated animals, VT conversion was noted in all animals and occurred after 51.7 .+-. 8.9 s (mean .+-. SE), with a VT threshold current elevation of 73.5 .+-. 11.2% above baseline at the time of conversion which progressed to 259 .+-. 44% of the initial value by 5.4 .+-. 0.5 min post-matrix placement. Lidocaine 1.4 .+-. 0.1 mg was delivered to the myocardium at the time of VT conversion (0.11 .+-. 0.01 mg/kg). In comparison, accelerated VT persisted for 5 min in three of five control animals, and progressed to ventricular fibrillation (VF) in the other two animals. In a separate series of eight dogs, the lidocaine-polyurethane matrixes were left in place for 4 h so that we could study the sustained antiarrhythmic action of controlled-release lidocaine on VT induction. The results of these experiments demonstrated a maintenance of the VT threshold elevation at a level of 53.9 .+-. 10.8% after 4 h, with a net lidocaine dose of 0.52 .+-. 0.06 mg/kg after 4 h of controlled release. Peripheral plasma levels of lidocaine during .ltoreq. 4 h of controlled release ranged from 93.9 to 158.5 ng/ml and were detectable only by fluorescent high-performance liquid chromatography (HPLC). However, regional coronary venous lidocaine levels were in the therapeutic range (1.15-2.63 .mu.g/ml) and remained relatively constant during 4 h of controlled release.