Kay, Victoria
Rickards, Caroline


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This study will assess how the human body responds to a decrease in blood volume entering the heart (central hypovolemia). Central hypovolemia leads to a decrease in blood flow to the brain, which can occur under various clinical conditions including hemorrhage and stroke. People have different tolerance to a decrease in central blood volume, and we want to determine the physiological mechanisms responsible for making some people more tolerant than others, with a particular focus on the role of blood flow and oxygen supply to the brain. We will also determine the potential mechanisms responsible for improved tolerance to central hypovolemia with a special breathing technique called inspiratory resistance breathing. Our goal is to determine how the body responds during decreased central blood volume, and if these mechanisms could be augmented to save lives during hemorrhage. These experiments may provide the clinical community with data to support the implementation of a diagnostic tool for assessing the level of bleeding by measuring brain oxygen levels. Moreover, by providing data to support the use of inspiratory resistance as a therapeutic intervention in the field, this technique could potentially save many lives by giving patients more time to reach a hospital where more advanced medical treatment can take place. Purpose (a): Tolerance to central hypovolemia varies between individuals, and recent studies have shown that protection of absolute cerebral blood flow is not an underlying mechanism. We hypothesized that subjects with high tolerance (HT) to central hypovolemia maintain cerebral oxygenation (ScO2) at higher levels of lower body negative pressure (LBNP) compared to their low tolerant (LT) counterparts, despite similar reductions in absolute flow. Methods (b): 15 healthy human subjects (10 male; 5 female) were instrumented for assessment of ScO2 (via near-infrared spectroscopy, NIRS) and mean middle cerebral artery velocity (MCAv; via transcranial Doppler, TCD). All subjects completed a presyncopal-limited lower body negative pressure (LBNP) protocol with an onset rate of 3 mmHg/min. Subjects who made it to ≥80mmHg LBNP were classified as HT, and subjects who made it to ≤70 mmHg LBNP were classified as LT. Results (c): The minimum difference in LBNP tolerance between the HT (N=6) and LT (N=9) group was 206 s (LT=1400±104 s vs. HT=2080±65 s; P=0.0003). Up to -45 mmHg LBNP, ScO2 was maintained in HT subjects (P≥0.538), while the LT (N=9) subjects had a progressive decrease in ScO2 (P≤0.016) from baseline. MCAv decreased from baseline in both HT and LT subjects (P≤0.022). There was a strong linear relationship between %∆ MCAv and %∆ ScO2 within the LT group (R2=0.98; P=0.013), whereas a weaker association between perfusion and oxygenation (R2=0.53; P=0.271) was observed in the HT group. Conclusions (d): In support of our hypothesis, higher tolerance to progressive central hypovolemia was associated with the protection of ScO2, despite an early and significant reduction in cerebral blood flow. This may have important clinical implications for the monitoring of cerebral perfusion and oxygenation in trauma patients.


Research Appreciation Day Award Winner - 2014 Cardiovascular Research Institute - 3rd Place Graduate Student