Background: Young males exhibit greater reductions in forearm tissue oxygenation (SmO2) during simulated hemorrhage compared with young females, and this response is attenuated when 10 second (~0.1 Hz) oscillations in arterial pressure and blood flow are experimentally induced. In young females, the reduction in SmO2 was smaller, so 0.1 Hz oscillations had no additional protective effect. However, there were two major limitations with this prior study: 1) SmO2 was only reduced by 10-15% with our method of simulated hemorrhage, and; 2) forearm blood flow was not assessed. To address these limitations, we developed a peripheral limb ischemia model which allows for a standardized 70-80% reduction in blood flow, and a 30-40% reduction in forearm SmO2, then re-examined if there was a sex difference in response to 0.1 Hz hemodynamic oscillations. Hypotheses: 1) The magnitude of local tissue hypoxia induced by severe ischemia will be smaller in women than men, and, subsequently; 2) 0.1 Hz oscillatory arterial pressure and blood flow will provide protection against this greater reduction in forearm SmO2 in men but not in women. Methods: Eight young and healthy human subjects (4M, 4F) completed two experimental protocols separated by ≥48 h. In both conditions, ischemia of the forearm was induced with a pneumatic cuff on the upper arm to decrease brachial artery (BA) blood velocity by ~70-80% from baseline. In the oscillation condition (OSC), 0.1 Hz oscillations in mean arterial pressure (MAP) and BA blood flow were then induced by inflating and deflating bilateral thigh cuffs every 5 seconds (0.1 Hz) throughout the forearm ischemia period. Thigh cuff inflations did not occur in the control condition (CON). BA conductance was calculated as blood flow divided by MAP. Results: The magnitude of forearm ischemia, indexed by the reduction in BA conductance, was similar between protocols within each sex (Males, CON: -85.2±4.7% vs. OSC: -80.1±9.9%, p=0.45; Females, CON: -72.4±8.2%; OSC: -73.4±5.6%, p=0.96), but was less overall in females vs. males (main effect of sex: p=0.07). While the %Δ in SmO2 was not different between males and females during CON (Males: -44.6±1.4% vs. Females: -32.7±8.0%, p=0.14), OSC attenuated this decrease in males but not females (Males: -22.0±11.8%, p=0.03; Females: -28.9±9.0%, p=0.71). To account for sex differences in the magnitude of forearm ischemia, the percent change in SmO2 was also normalized to the percent change in BA conductance (%Δ SmO2 / %Δ BA conductance). Consistent with the %Δ SmO2 responses, normalized SmO2 responses were similar between males and females during CON (Males: 0.52 ± 0.04%/% vs. Females: 0.45±0.09%/%, p=0.29), while OSC reduced the normalized SmO2 in males but not females (Males: 0.34±0.11%/%, p=0.01; Females; 0.39±0.12%, p=0.35). Conclusions: These results show that the magnitude of tissue hypoxia induced by a similar ischemic stimulus is not different between the sexes, but 0.1 Hz hemodynamic oscillations are more effective at protecting tissue oxygenation during ischemia in men than in women.
