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Objective To test theresuscitative effects from prolonged ventricular fibrillation by epinephrine combined with sodium-hydrogen exchanger isoform-1 inhibitor Cariporide. Methods 16 rats were received a 3 mg/kg bolus of Cariporide or the same volume of 0.9 % NaCl solution (control) 15seconds before completion 12 minutes untreated VF.Chest compression (CC) was started for a total of 8minutes. Adjusted the depth of compressor so that the aortic diastolic pressure to 25～ 28 mmHg during the 2nd minute of CC. Fix the depth of the piston and this depth was used throughout the remaining 6 minutes of CC. 10 seconds before starting the 3rd minute of chest compression, injected epinephrine (30 μg/kg) .Recorded the time at which restoration of spontaneous circulation (ROSC) occurred in Cariporide-treated rats. Electrical defibrillation was timed in control group to match the time of spontaneous defibrillation in Cariporide-treated rats. To the rats, which can’t be defibrillated spontaneously, received chest compression and rescues electrical shocks. Results compared with control group, with the same CC depth, Cariporide-treated rats received the higher and longer lasting coronary perfusion pressure (P ＜ 0.05), higher resuscitative rate ( P ＜ 0.05), less post resuscitative ventricular ectopic activities (P ＜ 0. 001), better hemodynamic effects and longer survival time (P ＜0.05) Conclusion Epinephrine combined with sodium-hydrogen exchanger isoform-1 inhibitor Cariporide may represent a novel and remarkably effective intervention for resuscitation from prolonged VF.