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Forty-four cosmonauts participating in 28 main long-term (73–438 days) missions on the Mir orbital station performed functional tests with graded physical exercise using a bicycle ergometer. There were two types of this functional load. The cosmonauts that participated in the first eight main missions performed a two-step exercise with a total load power of 1150 W. In the remaining cosmonauts, the exercise was three-step, with a total power of 1350 W. The results obtained during the flight were compared with the results of the same tests performed before the flight, which served as control values for each cosmonaut. To estimate the load tolerance, the heart rate (HR), systolic blood pressure, stroke volume (SV), cardiac output (CO), and cardiac index were analyzed. The data were grouped according to the load, taking into account the type of blood circulation for each group before and during the flight. The ratio between different types of blood circulation was found to change during the flight. The responses to both types of exercises before the flight were less favorable in the cases of the hyperkinetic type of circulation. In these cases, the dominance of the chronotropic function of the heart determined the increase in CO. In the cases of the hypo- and eukinetic types of circulation, the response to the exercise was close to normotonic. In microgravity, irrespective of the circulation type and the exercise, the mechanism of the CO formation changed: the effect of HR was dominant, and there was no increase in SV. Insufficient venous return to the chambers of the heart is the main cause of the decreased response of SV to exercises during spaceflight.