Anemia and Erythropoietin in Space Flights Natale G. De Santo, Massimo Cirillo, Karl A. Kirsch, Giacomo Correale, Christian Drummer, Waltraud Frassl, Alessandra F. Perna, Enzo Di Stazio, Luigi Bellini, and Hanns-Christian Gunga Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytoly- sis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at 6°, water immersion) and in rats provide further insight in unraveling the mechanism of astronauts’ anemia, a problem difficult to study in space because of the limited availability of spaceflights. Semin Nephrol 25:379-387 © 2005 Elsevier Inc. All rights reserved. KEYWORDS space, anemia, blood volume, plasma volume, astronauts, bed rest, head-down bed rest, water immersion, suspended rats, Gauer-Henry reflex T he history of space conquest started on October 4, 1957, when Russians launched Sputnik 1, which was followed by the manned mission of Yuri Gagarin on April 12, 1961, with Vostok 1. 1,2 The development of programs both by the Soviet Union and by the United States started the era of human adaptation to microgravity conditions, which is asso- ciated with significant organ alterations. In fact, our ancestral predecessors (Australopithecines) evolved in the Rift Valley of East Africa (under mild altitude hypoxia that was aggra- vated by colder and drier climates 3-6 ). Therefore, an increase in blood volume and an increase in red blood cell mass (RBCM) occurred. That also means that an increased whole- body oxygen transport capacity was acquired. In the same location they also acquired the bipedal position. Because of the height of the site (1,000-2,000 meters above sea level) their hemoglobin concentration increased and therefore hu- man beings now live with a surplus of 2 g/dL of hemoglobin (Hb). To survive, we need 77.5 mL of blood per kg of body weight, 70% of which is contained below heart level. 3-6 This is a unique condition. Human biology and human health in space became a hot topic by necessity and now we can exploit the knowledge obtained in space to handle diseases here on Earth. There- fore, it is not surprising if a very popular logo of the European Space Agency is for Research in Space for Health on Earth. The topic of anemia gives emphasis to this concept because it deals with a cause of anemia originating from RBCM exceed- ing bodily needs. Astronaut anemia immediately became a stimulating topic both for Soviet and United States missions. Interesting data were collected during Gemini IV and Gemini V missions, the former lasting 4 days and 56 minutes, the latter lasting 7 days, 18 hours, and 56 minutes. Plasma volume, red cell mass, and the total body-to-peripheral-hematocrit ratio were reduced. Data indicated a decrease of RBCM of 12.2% in Gemini IV and of 20% in Gemini V. Plasma volume under- went a reduction of 8.3% in Gemini IV and of 6.75% in Gemini V. The decrease in RBCM was seen as a result of a mild hemolysis of unknown cause. 7 In 1982, Cogoli 8 reviewed reports appearing from 1975 to 1979. 9-16 Figures 1 and 2 are based on those data 9-16 and 1st Chair of Nephrology, Second University of Naples, Naples, Italy; Depart- ment of Physiology Free University Berlin, Berlin, Germany; Department of Pharmacology, University of Aachen, Aachen, Germany; and the Cen- tro Gamma Laboratory, Montesarchio, Italy. Supported by ASI (N.G.D.S., M.C., and A.P.), and by DLR (K.A.K. and H.-C.G.) Address reprint requests to Natale G. De Santo, MD, 1st Chair of Nephrol- ogy, Second University of Naples, 5 Via Pansini, Pad 17, 80131 Naples, Italy.E-mail: nataleg.desanto@unina2.it 379 0270-9295/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.semnephrol.2005.05.006