['Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly occur after cardiac resuscitation compromising the return of stable circulation. We investigated in a pig model of VF whether limiting Na(+)-induced cytosolic Ca(2+) overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) inhibitor cariporide promotes resuscitation with stable circulation.', 'VF was electrically induced in 20 male pigs and left untreated for 6 min after which CPR was initiated and continued for 8 min before attempting defibrillation. Pigs were randomized to receive 3-mg/kg cariporide (n=10) or 0.9%-NaCl (n=10) before chest compression.', 'Seven of 10 pigs in each group were successfully resuscitated and survived 2h. Cariporide ameliorated post-resuscitation ventricular ectopic activity such that fewer singlets (5+/-5 vs. 26+/-21; p<0.05) and fewer bigemini (1+/-3 vs. 33+/-25; p<0.05) were observed during the initial 5 min post-resuscitation. Additionally, cariporide-treated pigs did not require additional post-resuscitation shocks for ventricular tachycardia or recurrent VF (0.0+/-0.0 vs. 5.3+/-7.8 shocks; p=0.073). During the initial 60 min cariporide-treated pigs had higher, cardiac index (6.1+/-0.7 vs. 4.4+/-1.1L/min/m(2); p<0.01), left ventricular stroke work index (45+/-9 vs. 36+/-10 gmm/beat/m(2); p<0.05), and numerically higher mean aortic pressure (104+/-11 vs. 91+/-12 mmHg; p=0.054).'] Does cariporide given during resuscitation promote return of electrically stable and mechanically competent cardiac activity?