Impact of environmental stressors on tolerance to hemorrhage in humans

Hemorrhage is a leading cause of death in military and civilian settings, and ~85% of potentially survivable battlefield deaths are hemorrhage-related. Soldiers and civilians are exposed to a number of environmental and physiological conditions that have the potential to alter tolerance to a hemorrhagic insult. The objective of this review is to summarize the known impact of commonly encountered environmental and physiological conditions on tolerance to hemorrhagic insult, primarily in humans. The majority of the studies used lower body negative pressure (LBNP) to simulate a hemorrhagic insult, although some studies employed incremental blood withdrawal. This review addresses, first, the use of LBNP as a model of hemorrhage-induced central hypovolemia and, then, the effects of the following conditions on tolerance to LBNP: passive and exercise-induced heat stress with and without hypohydration/dehydration, exposure to hypothermia, and exposure to altitude/hypoxia. An understanding of the effects of these environmental and physiological conditions on responses to a hemorrhagic challenge, including tolerance, can enable development and implementation of targeted strategies and interventions to reduce the impact of such conditions on tolerance to a hemorrhagic insult and, ultimately, improve survival from blood loss injuries.

Download Full-text

The impact of menopausal status on cardiac responses to exercise training and lower body negative pressure

Maturitas ◽

10.1016/j.maturitas.2017.06.010 ◽

2017 ◽

Vol 103 ◽

pp. 91

Author(s):

Amanda Q.X. Nio ◽

Eric J. Stöhr ◽

Samantha Rogers ◽

Rachel Mynors-Wallis ◽

Jane M. Black ◽

...

Keyword(s):

Exercise Training ◽

Negative Pressure ◽

Lower Body Negative Pressure ◽

Menopausal Status ◽

Lower Body ◽

Cardiac Responses ◽

The Impact

Download Full-text

Sweat loss during heat stress contributes to subsequent reductions in lower-body negative pressure tolerance

Experimental Physiology ◽

10.1113/expphysiol.2012.068171 ◽

2012 ◽

Vol 98 (2) ◽

pp. 473-480 ◽

Cited By ~ 21

Author(s):

Rebekah A. I. Lucas ◽

Matthew S. Ganio ◽

James Pearson ◽

Craig G. Crandall

Keyword(s):

Heat Stress ◽

Negative Pressure ◽

Lower Body Negative Pressure ◽

Lower Body ◽

Sweat Loss ◽

Pressure Tolerance

Download Full-text

Blood Coagulation during Lower Body Negative Pressure vs. Blood Loss in Humans

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.823.3 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Noud Helmond ◽

Blair Johnson ◽

Timothy Curry ◽

Andrew Cap ◽

Victor Convertino ◽

...

Keyword(s):

Blood Loss ◽

Blood Coagulation ◽

Negative Pressure ◽

Lower Body Negative Pressure ◽

Lower Body

Download Full-text

Cerebral blood flow regulation during blood loss compared to lower body negative pressure in humans (1068.9)

The FASEB Journal ◽

10.1096/fasebj.28.1_supplement.1068.9 ◽

2014 ◽

Vol 28 (S1) ◽

Author(s):

Jill Barnes ◽

Blair Johnson ◽

Victor Convertino ◽

Michael Joyner ◽

Caroline Rickards

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Blood Loss ◽

Negative Pressure ◽

Lower Body Negative Pressure ◽

Flow Regulation ◽

Lower Body ◽

Blood Flow Regulation

Download Full-text

Coagulation changes during lower body negative pressure and blood loss in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00435.2015 ◽

2015 ◽

Vol 309 (9) ◽

pp. H1591-H1597 ◽

Cited By ~ 20

Author(s):

Noud van Helmond ◽

Blair D. Johnson ◽

Timothy B. Curry ◽

Andrew P. Cap ◽

Victor A. Convertino ◽

...

Keyword(s):

Blood Loss ◽

Negative Pressure ◽

Lower Body Negative Pressure ◽

Venous Pressure ◽

Regression Line ◽

Lower Body ◽

Stimulus Response ◽

Arterial Blood ◽

Three Stages ◽

Α Angle

We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, −15, −30, and −45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to −45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG α° angle (−0.42 ± 0.96 during LBNP vs. −2.41 ± 1.13°/mmHg during BL; P < 0.05). During both LBNP and BL, coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 ± 2.4 to 6.2 ± 1.1; BL, 8.7 ± 1.3 to 6.4 ± 0.4 min; both P < 0.05). Our results indicate that LBNP models the general changes in coagulation markers observed during BL.

Download Full-text

The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage

Experimental Biology and Medicine ◽

10.1177/1535370217694099 ◽

2017 ◽

Vol 242 (8) ◽

pp. 874-883 ◽

Cited By ~ 30

Author(s):

Alicia M Schiller ◽

Jeffrey T Howard ◽

Victor A Convertino

Keyword(s):

Blood Loss ◽

Blood Volume ◽

Negative Pressure ◽

Time Course ◽

Tissue Oxygenation ◽

Lower Body Negative Pressure ◽

Lower Body ◽

Central Blood Volume ◽

Volume Loss ◽

Physiological Mechanisms

The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive reductions in central blood volume similar to those reported during actual hemorrhage in conscious humans to the onset of hemodynamic decompensation (i.e. early phase of decompensatory shock), and is repeatable in the same subject. Understanding the fundamental underlying physiology of human hemorrhage helps to test paradigms of critical care medicine, and identify and develop novel clinical practices and technologies for advanced diagnostics and therapeutics in patients with life-threatening blood loss.

Download Full-text

Divergent roles of plasma osmolality and the baroreflex on sweating and skin blood flow

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00411.2011 ◽

2012 ◽

Vol 302 (5) ◽

pp. R634-R642 ◽

Cited By ~ 24

Author(s):

Aaron G. Lynn ◽

Daniel Gagnon ◽

Konrad Binder ◽

Robert C. Boushel ◽

Glen P. Kenny

Keyword(s):

Blood Flow ◽

Heat Stress ◽

Core Temperature ◽

Skin Blood Flow ◽

Negative Pressure ◽

Lower Body Negative Pressure ◽

Plasma Osmolality ◽

Whole Body ◽

Lower Body ◽

Change In Mean

Plasma hyperosmolality and baroreceptor unloading have been shown to independently influence the heat loss responses of sweating and cutaneous vasodilation. However, their combined effects remain unresolved. On four separate occasions, eight males were passively heated with a liquid-conditioned suit to 1.0°C above baseline core temperature during a resting isosmotic state (infusion of 0.9% NaCl saline) with (LBNP) and without (CON) application of lower-body negative pressure (−40 cmH2O) and during a hyperosmotic state (infusion of 3.0% NaCl saline) with (LBNP + HYP) and without (HYP) application of lower-body negative pressure. Forearm sweat rate (ventilated capsule) and skin blood flow (laser-Doppler), as well as core (esophageal) and mean skin temperatures, were measured continuously. Plasma osmolality increased by ∼10 mosmol/kgH2O during HYP and HYP + LBNP conditions, whereas it remained unchanged during CON and LBNP ( P ≤ 0.05). The change in mean body temperature (0.8 × core temperature + 0.2 × mean skin temperature) at the onset threshold for increases in cutaneous vascular conductance (CVC) was significantly greater during LBNP (0.56 ± 0.24°C) and HYP (0.69 ± 0.36°C) conditions compared with CON (0.28 ± 0.23°C, P ≤ 0.05). Additionally, the onset threshold for CVC during LBNP + HYP (0.88 ± 0.33°C) was significantly greater than CON and LBNP conditions ( P ≤ 0.05). In contrast, onset thresholds for sweating were not different during LBNP (0.50 ± 0.18°C) compared with CON (0.46 ± 0.26°C, P = 0.950) but were elevated ( P ≤ 0.05) similarly during HYP (0.91 ± 0.37°C) and LBNP + HYP (0.94 ± 0.40°C). Our findings show an additive effect of hyperosmolality and baroreceptor unloading on the onset threshold for increases in CVC during whole body heat stress. In contrast, the onset threshold for sweating during heat stress was only elevated by hyperosmolality with no effect of the baroreflex.

Download Full-text