Effects of physical activity and gravitational stress on cardiovascular control

Sammanfattning: The long-term goal of the present work was to characterize the responses to gravitational challenges in exercising humans after long-term head-down-tilt bedrest (HDT). HDT is a simulation of weightlessness with respect to effects on the systemic circulation, and previous studies in resting men have suggested that impairments of arterial baroreflexes contribute to the orthostatic intolerance seen after HDT and spaceflight. However, orthostatic challenges are commonly associated with physical activity, so a characterization of cardiovascular responses to gravitational challenges during exercise rather than rest was considered to provide more physiologically relevant information. Furthermore, it was hypothezised that cardiovascular impairments, if any, would be caused by hemodynamic rather than baroreflex mechanisms. In a first step, we studied the applicability during exercise of methods developed for studies of baroreflexes in resting humans. Such methods include apnea during short-lasting carotid sinus stimulation, and they assume a fixed temporal coupling between carotid stimulus and cardiac response. In the present exercise experiments it was found that apnea induced marked bradycardia and hypertension that tended to confound all but the first 5 s of the response to a carotid stimulation initiated 4-5 s after the onset of apnea. Also, both orthostatic stress and exercise were associated with a variable latency of the carotidcardiac baroreflex. In keeping with these findings an alternative mode of baroreflex stimulation, including rapid tilting during eupnea, was developed for exercise studies. In a second step, the cardiovascular responses to rapid tilting were studied in healthy exercising men. The tilts induced a complex pattern of arterial pressure (AP) fluctuations: The efficiency of the skeletal muscle pump promptly changed with posture and with an equally prompt effect on the (virtual) total peripheral conductance. There are also changes in AP at heart level were induced because the heart is located cranial from the hydrostatic indifferent point. In addition, during tilt from upright to supine there were indications that left ventricular stroke volume (SV) transiently decreased due to a rapid increase in right ventricular preload, which acted to impede left ventricular filling (direct ventricular interdependence). The baroreflex control of heart rate (HR) was analyzed with a dynamic model in which HR was a basically linear function of AP recorded at a site between the heart and the carotid sinus. Non-linearities of the FIR responses could be modelled as a result of varying fractional contributions of fast vagal and slow sympathetic HR responses. In a third step, baroreflex and hemodynamic responses were studied in exercising men before and after six weeks of strict HDT. HDT did not alter arterial-cardiac baroreflex sensitivity during light exercise, which is in contrast to previous findings obtained during supine resting conditions. The indices of direct ventricular interdependence were abolished immediately after long-term bedrest; it is suggested that an initial hypovolemia brought about smaller exercise heart volumes, and that the restrictive action of the pericardium was decreased. Within two days, when the plasma volume had been restored, the signs of ventricular interdependence returned to control values. The cardiovascular responses to exercise after long-term strict bedrest differed from those seen after bed rest of shorter duration and after space flights that included exercise countermeasures. Thus, in the present study there were prominent decreases of SV in both supine and upright exercise (-25±3% and -30±5%, respectively). The decrease in SV during submaximal exercise persisted even after the bed-rest-induced plasma hypovolemia had normalized. There was a more complete recovery of SV and cardiac output during upright exercise compared to exercise in the supine position, where SV had not recovered fully after one month. This suggests a stiffer, and probably smaller, heart that was unable to increase SV with the increased preload induced by supine exercise. It is concluded that cardiovascular impairments in exercising men after long-term bedrest are of hemodynamic rather than of baroreflex origin.