BACKGROUND: During resuscitation, fibrillation often recurs. In swine, we studied refibrillation after long-duration ventricular fibrillation, investigating an association with chest compressions (CCs). METHODS AND RESULTS: In protocol A, 47 episodes of long-duration ventricular fibrillation lasting at least 2.5 minutes were induced in 8 animals. After defibrillation, CCs were required for 35 episodes and delivered with a pneumatic device (Lucas cardiopulmonary resuscitation). In 9 episodes, refibrillation occurred within 2 seconds of CC initiation (group 1) and in 26 episodes, CCs were delivered without refibrillation (group 2). From the ECG and intracardiac electrodes, the RR interval preceding CCs, the shortest cycle length during the first 2 CCs (short), and the preceding cycle length (long) were measured. A similar study was conducted in 3 more animals without intracardiac catheters (protocol B). In protocol A, the mean RR before CC was 665+/-292 ms in group 1 and 769+/-316 in group 2. CCs stimulated ventricular beats in all 35 episodes. The short and long intervals were shorter in group 1 (215+/-31 and 552+/-210 ms) than in group 2 (402+/-153 and 699+/-147 ms) (P=0.009 and P=0.04, respectively). The prematurity index (short/RR) was lower in group 1 than in group 2 (0.35+/-0.09 vs 0.58+/-0.21; P<0.01). A short interval <231 ms predicted refibrillation with 88% sensitivity and 91% specificity. In protocol B, CCs were required in 11 episodes, causing ventricular stimulation in all of them and ventricular fibrillation within the first 2 CCs in 3. CONCLUSIONS: Under some conditions, CC during resuscitation can stimulate the ventricles and initiate ventricular fibrillation by a long-short sequence.