Geert Kleinnibbelink

Exercise-Induced Cardiac Function under Hypoxia 2 55 of hypoxia on EICF may be that the exaggerated loading conditions under hypoxia were not sufficient enough at 3000m of simulated altitude, and/or the exposure time to the raised afterload of the RV was not long enough to contribute to the EICF magnitude. There are also indications that hypoxia itself may induce cardiac dysfunction due to sustained low oxygen availability, however, this seems mainly during prolonged exposure. 41 Our hypothesis originated from the accepted phenomenon of disproportionately higher relative wall stress in the RV compared to the LV during exercise, but also based on observations suggesting a larger magnitude of EICF in the RV compared to the LV. 11, 14, 15 For example, Stewart et al. examined the influence of high-intensity exercise on RV free wall and segmental LV strain EICF following 90 minutes cycling 10 , and found that the reduction in strain was more profound in the RV than in the LV. In their study they demonstrated a relative reduction in RV strain of -17.5% compared to -9.8% in our study, which supports a dose-response relationship. Our study is the first to our knowledge to directly compare normoxic and hypoxic conditions on EICF, and demonstrated similar changes in both RV and the LV. Although mechanical changes in the RV and LV are independent of each other 27 , and likely differ during exercise, our work suggests that (after)load dependency may be a less contributing factor to EICF as previously suggested. Alternatively, intrinsic myocardial factors such as β -adrenergic receptor desensitization 7, 42 and oxidative stress 43 may play a more substantial role. Our study, however, is unable to provide further insight into these other possible mechanisms. It is also of interest that following the 45-minute high-intensity exercise, this study showed a lack of any RV dilation (no rightward shift strain-area loop, Figure 4 ) as previously demonstrated following prolonged exercise. 27 Previous studies have demonstrated a serial and parallel impact from ventricular interdependence on LV filling secondary to RV volume / pressure overload. 27, 44 This finding is consistent with other studies of high-intensity exercise of relative short durations rather than is seen in EICF studies of prolonged exercise highlighting a possible dose response related to both intensity and duration. 10, 14, 27 In the shorter duration exercise intervention studies, the reduction in LV size occurs irrespective of changes in RV size which provides additional support for an intrinsic mechanism independent to both the right and left side of the heart. Moreover, the decreased uncoupling in the strain-area loop ( Figure 4 ), indicating less longitudinal