Abstract
Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Lower body negative pressure (LBNP) is a validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of maximal, pre-syncopal limited LBNP. Fifteen healthy human subjects (11 M/4 F; age 27 ± 1 y) were recruited for a single LBNP experiment to presyncope (chamber pressure was progressively reduced every 5-min in a stepwise manner). Heart rate was assessed via ECG, arterial pressure and stroke volume (SV) were measured continuously via finger photoplethysmography, muscle oxygen saturation (SmO 2 ) was measured via near-infrared spectroscopy, and venous blood samples were collected at baseline and presyncope. Plasma samples were analyzed for F 2 -isoprostanes (F 2 -IsoP), a global marker of oxidative stress. The magnitude of central hypovolemia, indexed by the maximal decrease (%Δ) in SV, ranged from 27 to 74% (53.5 ± 3.9%; P < 0.001), and mean arterial pressure (MAP) decreased by 12.6 ± 2.6% (P < 0.001 vs. pre-LBNP baseline). F 2 -IsoP increased by 28.5 ± 11.6% (P = 0.05) from baseline (24 ± 2 pg/mL) to presyncope (29 ± 3 pg/mL). The increase in F 2 -IsoP was not associated with %Δ SV (r = 0.21, P = 0.46), %Δ MAP (r = 0.05, P = 0.86), %Δ SmO 2 (r = 0.05, P = 0.90), or the maximum level of LBNP attained (r = 0.35, P = 0.20). Simulated hemorrhage induced by LBNP to presyncope elicited an increase in oxidative stress, but this response was not associated with the magnitude of central hypovolemia, hypotension, or the decrease in peripheral muscle tissue oxygen saturation. These findings have important implications for the study of hemorrhage using LBNP, and future investigations of interventions targeting oxidative stress. Impact statement: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F 2 -isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.
| Original language | English |
|---|---|
| Pages (from-to) | 272-278 |
| Number of pages | 7 |
| Journal | Experimental Biology and Medicine |
| Volume | 244 |
| Issue number | 3 |
| DOIs | |
| State | Published - 1 Mar 2019 |
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Keywords
- F2-isoprostanes
- blood loss
- cardiovascular
- human subjects
- lower body negative pressure
- oxidative
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Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults. / Park, Flora S.; Kay, Victoria L.; Sprick, Justin D.; Rosenberg, Alexander J.; Anderson, Garen K.; Mallet, Robert T.; Rickards, Caroline Alice.
In: Experimental Biology and Medicine, Vol. 244, No. 3, 01.03.2019, p. 272-278.Research output: Contribution to journal › Article
TY - JOUR
T1 - Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults
AU - Park, Flora S.
AU - Kay, Victoria L.
AU - Sprick, Justin D.
AU - Rosenberg, Alexander J.
AU - Anderson, Garen K.
AU - Mallet, Robert T.
AU - Rickards, Caroline Alice
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Lower body negative pressure (LBNP) is a validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of maximal, pre-syncopal limited LBNP. Fifteen healthy human subjects (11 M/4 F; age 27 ± 1 y) were recruited for a single LBNP experiment to presyncope (chamber pressure was progressively reduced every 5-min in a stepwise manner). Heart rate was assessed via ECG, arterial pressure and stroke volume (SV) were measured continuously via finger photoplethysmography, muscle oxygen saturation (SmO 2 ) was measured via near-infrared spectroscopy, and venous blood samples were collected at baseline and presyncope. Plasma samples were analyzed for F 2 -isoprostanes (F 2 -IsoP), a global marker of oxidative stress. The magnitude of central hypovolemia, indexed by the maximal decrease (%Δ) in SV, ranged from 27 to 74% (53.5 ± 3.9%; P < 0.001), and mean arterial pressure (MAP) decreased by 12.6 ± 2.6% (P < 0.001 vs. pre-LBNP baseline). F 2 -IsoP increased by 28.5 ± 11.6% (P = 0.05) from baseline (24 ± 2 pg/mL) to presyncope (29 ± 3 pg/mL). The increase in F 2 -IsoP was not associated with %Δ SV (r = 0.21, P = 0.46), %Δ MAP (r = 0.05, P = 0.86), %Δ SmO 2 (r = 0.05, P = 0.90), or the maximum level of LBNP attained (r = 0.35, P = 0.20). Simulated hemorrhage induced by LBNP to presyncope elicited an increase in oxidative stress, but this response was not associated with the magnitude of central hypovolemia, hypotension, or the decrease in peripheral muscle tissue oxygen saturation. These findings have important implications for the study of hemorrhage using LBNP, and future investigations of interventions targeting oxidative stress. Impact statement: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F 2 -isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.
AB - Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Lower body negative pressure (LBNP) is a validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of maximal, pre-syncopal limited LBNP. Fifteen healthy human subjects (11 M/4 F; age 27 ± 1 y) were recruited for a single LBNP experiment to presyncope (chamber pressure was progressively reduced every 5-min in a stepwise manner). Heart rate was assessed via ECG, arterial pressure and stroke volume (SV) were measured continuously via finger photoplethysmography, muscle oxygen saturation (SmO 2 ) was measured via near-infrared spectroscopy, and venous blood samples were collected at baseline and presyncope. Plasma samples were analyzed for F 2 -isoprostanes (F 2 -IsoP), a global marker of oxidative stress. The magnitude of central hypovolemia, indexed by the maximal decrease (%Δ) in SV, ranged from 27 to 74% (53.5 ± 3.9%; P < 0.001), and mean arterial pressure (MAP) decreased by 12.6 ± 2.6% (P < 0.001 vs. pre-LBNP baseline). F 2 -IsoP increased by 28.5 ± 11.6% (P = 0.05) from baseline (24 ± 2 pg/mL) to presyncope (29 ± 3 pg/mL). The increase in F 2 -IsoP was not associated with %Δ SV (r = 0.21, P = 0.46), %Δ MAP (r = 0.05, P = 0.86), %Δ SmO 2 (r = 0.05, P = 0.90), or the maximum level of LBNP attained (r = 0.35, P = 0.20). Simulated hemorrhage induced by LBNP to presyncope elicited an increase in oxidative stress, but this response was not associated with the magnitude of central hypovolemia, hypotension, or the decrease in peripheral muscle tissue oxygen saturation. These findings have important implications for the study of hemorrhage using LBNP, and future investigations of interventions targeting oxidative stress. Impact statement: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F 2 -isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.
KW - F2-isoprostanes
KW - blood loss
KW - cardiovascular
KW - human subjects
KW - lower body negative pressure
KW - oxidative
UR - http://www.scopus.com/inward/record.url?scp=85061592237&partnerID=8YFLogxK
U2 - 10.1177/1535370219828706
DO - 10.1177/1535370219828706
M3 - Article
C2 - 30727766
AN - SCOPUS:85061592237
VL - 244
SP - 272
EP - 278
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 1535-3702
IS - 3
ER -