Study protocol. Heparin was infused to maintain an active clotting time of 180 to 220 sec after ECMO cannulation during the whole experiment. Of the 20 sheep, two were used for angiography. The other 18 sheep were randomly assigned to undertake one of three cannulation procedures. After 15 min of ECMO, ARF was initiated by removing the ventilator and discontinuing mechanical ventilation. The ARF animals were supported with IVC-FA for another 15 min and then were shifted to SVC-FA, IVC-CA or FA-IJV depending on the group assignment. The black arrow indicates the drainage cannula and the white arrow indicates the return cannula. Comparisons between IVC-FA and SVC-FA, IVC-FA and IVC-CA and IVC-FA and FA-IJV were made with paired t test. ARF: acute respiratory failure; ECMO: extracorporeal membrane oxygenation; FA-IJV: an additional return cannula was added into the internal jugular vein on the basis of femoral veno-arterial extracorporeal membrane oxygenation; IVC-CA: a drainage cannula was inserted into the inferior vena cava and a return cannula was inserted into the carotid artery; IVC-FA: a drainage cannula was placed into the inferior vena cava through the femoral vein and a return cannula was inserted into the femoral artery; SVC-FA: a drainage cannula was placed into the superior vena cava through the femoral vein and a return cannula was placed into the femoral artery.