To minimize the risk of rejection, an immunosuppression regimen informed by current practices in clinical transplantation, and previously described for use in xeno-support of human lungs, was used (Fig. 1b).14 ,15 (link) At 4 h before cross-circulation, xeno-support swine were anesthetized, intubated and administered cobra venom factor (CVF, 1 mg; Sigma-Aldrich) to deplete complement activity.16 Intravenous diphenhydramine (50 mg; West-Ward) and methylprednisolone (1 g; Pfizer) were administered to limit the inflammatory response associated with CVF. Intravenous tacrolimus (5 mg; Astellas) and mycophenolate (500 mg; Genentech) were also administered prior to reperfusion and re-dosed every 12 hours (Fig. S1c). methylprednisolone (125 mg; Pfizer) was re-administered every 8 hours after the initial dose.