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Objective: To determine whether the administration of intra-arrest cyclosporine (CCY) and methylprednisolone (MP) preserves left ventricular ejection fraction (LVEF) and cardiac output (CO) after return of spontaneous circulation (ROSC)., Methods: Eleven, 25-30kg female swine were randomized to receive 10mg/kg CCY + 40mg MP or placebo, anesthetized and given a transthoracic shock to induce ventricular fibrillation. After 8 minutes, standard CPR was started. After two additional minutes, the experimental agent was administered. Animals with ROSC were supported for up to 12h with norepinephrine as needed. Echocardiography was performed at baseline, and 1, 2, 6 and 12h post-ROSC. Analysis was performed using generalized estimating equations (GEE) after downsampling continuously sampled data to 5 minute epochs., Results: Eight animals (64%) achieved ROSC after a median of 7 [IQR 5-13] min of CPR, 2 [ IQR 1-3] doses of epinephrine and 2 [IQR 1-5] defibrillation shocks. Animals receiving CCY+MP had higher post ROSC MAP (GEE coefficient -10.2, P = <0.01), but reduced cardiac output (GEE coefficient 0.8, P = <0.01) compared to placebo. There was no difference in LVEF or vasopressor use between arms., Conclusions: Intra-arrest cyclosporine and methylprednisolone decreased post-arrest cardiac output and increased mean arterial pressure without affecting left ventricular ejection fraction.