approved by the FDA and was marketed as a blood substitute in the United States from 1989 through 1994 when it was withdrawn from the market due to poor sales. Perftoran was approved in the Soviet Union in 1994 and remained in limited use in Russia at least as late as 2019. The second approach to oxygen delivery tested a perfluorocarbon emulsion not as a blood substitute, but rather as a cerebrospinal fluid (CSF) substitute. In order to increase oxygen delivery to the brains of patients that had reduced blood flow due to acute ischemic stroke, artificial CSF mixed with pre-oxygenated perfluorocarbon emulsion was continuously added into the skull by a ventricular catheter while CSF was continuously removed by a lumbar catheter. Animal studies in cats with acute ischemic stroke showed very strong results, so a clinical trial in four humans was conducted. All four patients survived for 30 days to 2 years before dying of other causes. Enrollment in the trial was slow however, which caused the funding for the project to be cut. A third approach to oxygen delivery is to move perfluorocarbon molecules into positions where they can enhance the flow of oxygen through the lower parts of the oxygen cascade. While it is difficult to observe the positioning of the perfluorocarbon molecules directly, molecules positioned in the right places between red blood cells and mitochondria may reduce resistance to oxygen flow. In cases where the oxygen tension at the mitochondria are very low, this would expose nearby red blood cells to lower oxygen tensions and cause them to offload more oxygen as described by the oxygen–hemoglobin dissociation curve. The most notable example is dodecafluoropentane emulsion (DDFPe, formerly EchoGen, now NanO2). The drug is injected intravenously then the perfluorocarbon molecules then spread widely before eventually passing through the lungs whey they are evaporated and exhaled. The drug showed very strong results in animal studies of acute ischemic stroke, heart attack and other indications. The drug was tested in a Phase Ib/II clinical trial in 24 patients who had reduced blood flow to the brain due to acute ischemic stroke, where it was intended to increase oxygen delivery to the brain to keep the tissue alive until blood flow could be normalized. The high dose group of patients in the clinical trial had improved functional independence compared to placebo, though the number of patients tested was small and