Browsing by Subject "hemorrhage"
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Item Sex Differences in Oxidative Stress and Inflammation Responses During and After Simulated Hemorrhage(2020-05) Barnes, Haley J.; Rickards, Caroline A.; Hodge, Lisa M.; Mallet, Robert T.; Goulopoulou, StylianiHemorrhage (i.e., massive blood loss) induces an oxidative stress and inflammatory response that can persist even following hemostasis and resuscitation. Premenopausal females exhibit a survival advantage following hemorrhage compared to young males. In this study, we hypothesized that young males would elicit a greater oxidative stress and inflammatory response compared to young females, both during and after a simulated hemorrhage via lower body negative pressure (LBNP). Young, healthy human subjects (10F; 10M) participated in a stepwise-LBNP protocol to presyncope. Venous blood samples were collected at baseline, presyncope, and 1-h into recovery (i.e., following "resuscitation"). The oxidative stress response was assessed via circulating F2-isoprostanes (F2-IsoP) using gas chromatography-negative ion chemical ionization-mass spectrometry. The inflammatory response was assessed via circulating tissue necrosis factor-α (TNF-α), C-Reactive Protein (CRP), thymus and activation-regulated chemokine (TARC), and interleukin (IL)-5, IL-6, IL-7, and IL-10, using a MSD® Multiplex assay. LBNP tolerance time was similar between male and female subjects (Males, 1592±124 s vs. Females, 1437 ± 113 s; P = 0.37). There was no effect of time or sex on the absolute or relative change in F2-IsoP during or after LBNP (P ≥ 0.12). However, male subjects exhibited a greater pro-and anti-inflammatory response during and after LBNP compared to female subjects (Notable markers at 1-h recovery compared to baseline, IL-6: Males, 101.4 ± 138.9% vs. Females, 12.3 ± 34.0%, P = 0.06; IL-10: Males, 71.1 ± 133.3% vs. Females, -2.2 ± 11.8%; P = 0.06). These data suggest that there may be a potential sex difference in the inflammatory response to simulated hemorrhage.Item The Role of Cerebral Oxygenation and Perfusion on Tolerance to Central Hypovolemia(2016-12-01) Kay, Victoria L.; Caroline A. Rickards; Robert T. Mallet; Michael L. SmithTolerance to central hypovolemia, including hemorrhage, is highly variable between individuals. The role of cerebral oxygenation and regional cerebral perfusion on tolerance to central hypovolemia has not been explored. Protection of posterior cerebral perfusion may be an important factor in tolerance, as the posterior circulation supplies blood to the autonomic and respiratory control centers in the brain stem. Additionally, despite the reduction in cerebral oxygen delivery with central hypovolemia via decreased flow, the role of compensatory increases in oxygen extraction and subsequent cerebral tissue oxygenation on tolerance have not been identified. The oscillatory pattern of cerebral blood flow has recently been identified as a contributing factor to improving tolerance to central hypovolemia, and may be more important than the protection of absolute flow. This finding was demonstrated when comparing high vs. low tolerant individuals, and in subjects who exhibited increased tolerance to central hypovolemia while breathing against inspiratory resistance. We hypothesized that healthy human subjects with naturally high tolerance to central hypovolemia, and subjects breathing against inspiratory resistance under hypovolemic stress would exhibit 1) protection of cerebral oxygen saturation (ScO2); 2) prolonged preservation of cerebral blood flow in the posterior versus anterior cerebral circulation, and; 3) higher LF oscillations in cerebral blood flow. The major findings from these investigations are: 1) subjects with high tolerance to central hypovolemia exhibited protection of ScO2 and velocity in the posterior cerebral circulation; 2) LF oscillations did not play a role in the protection of ScO2; 3) resistance breathing improved tolerance to central hypovolemia, but not via protection of ScO2 or velocity in either the anterior or posterior cerebral circulation, and; 4) resistance breathing was associated with increased high frequency oscillatory power in arterial pressure, anterior and posterior cerebral blood velocity, and ScO2. We conclude that individuals with naturally high tolerance to central hypovolemia exhibit protection of cerebral tissue oxygenation and prolonged preservation of perfusion within the posterior cerebral circulation, but not in the anterior circulation, thus delaying the onset of presyncope. Improved tolerance to central hypovolemia via resistance breathing was not related to these mechanisms, but may have been associated with increased depth of breathing, subsequently decreasing intracranial pressure and increasing cerebral perfusion pressure.Item THE ROLE OF CEREBRAL OXYGENATION ON TOLERANCE TO CENTRAL HYPOVOLEMIA(2014-03) Kay, Victoria; Rickards, CarolineThis 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.