Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Cerebral Blood‐Flow Regulation During Hemorrhage

Caroline A. Rickards

10.1002/cphy.c140058

Source: Volume 5, Issue 4, October 2015

Published online: September 2015

Full Article on Wiley Online Library



ABSTRACT

Massive uncontrolled blood loss can occur under a variety of conditions including trauma, as a complication of childbirth or surgery, ruptured ulcers, clotting disorders, and hemorrhagic fevers. Across the continuum of hemorrhage, loss of blood volume is a significant challenge to the maintenance of cerebral perfusion. During the initial stages of hemorrhage, reflex mechanisms are activated to protect cerebral perfusion, but persistent blood loss will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Hemorrhage represents a unique physiological stress to the brain, as it influences each of these regulatory mechanisms, resulting in complex interplay that ultimately challenges the ability of the brain to maintain adequate perfusion. Early studies of actual hemorrhage in humans employed blood loss protocols up to 1000 mL, but did not include any measurements of cerebral blood flow. As ethical considerations necessarily constrain the use of human volunteers for massive blood loss studies that induce irreversible shock, most of what is known about cerebral blood‐flow responses to hemorrhage has been determined from animal models. Limitations of species differences regarding regulatory mechanisms, anatomy, and the effect of anesthesia, however, must be considered. Advances in monitoring technologies, and a recent renewed interest in understanding cerebral blood‐flow regulation in humans, however, is rapidly accelerating knowledge in this field. © 2015 American Physiological Society. Compr Physiol 5:1585‐1621, 2015.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Hemodynamic responses to a 1020 mL hemorrhage in a healthy human subject. Right auricular pressure (RAP) and cardiac output (CO) fall progressively, while heart rate (HR) and total peripheral resistance (TPR) increase via a baroreflex‐mediated mechanism. Blood pressure (BP) is maintained until HR and TPR fall precipitously at the onset of syncope (faint). Redrawn from (18) with permission from Elsevier.
Figure 2. Figure 2. Physiological factors affecting cerebral blood flow during hemorrhage. The ultimate response of cerebral blood flow depends upon the strength and magnitude of each stimulus independently, and the combined interrelationship between all factors.
Figure 3. Figure 3.

(A) The major extracranial vessels supplying the Circle of Willis include the left and right internal carotid arteries (ICA), and the left and right vertebral arteries (VA) fusing to form the basilar artery (BA). The ICAs feed the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA), and the BA feeds the posterior cerebral arteries (PCA). Reprinted with permission (58).

(B) The major intracranial vessels form the Circle of Willis. ACA, anterior cerebral artery; AComA, anterior communicating artery; MCA, middle cerebral artery; ICA, internal carotid artery; PCA, posterior cerebral artery; PComA, posterior communicating artery; SCA, superior cerebellar artery; Basilar A, basilar artery. Reprinted with permission (56).

Figure 4. Figure 4. Summary of findings from four studies assessing changes in middle cerebral artery diameter (MCA) with perturbations in arterial CO2 using MRI technology. These studies indicate that there may be a threshold level of hypo‐ and hypercapnia that induces changes in MCA diameter (between 7% and 10% from baseline). Reprinted with permission (8).
Figure 5. Figure 5. Duplex‐Doppler ultrasound images in a human subject of the vertebral artery (VA), basilar artery (BA), internal carotid artery (ICA), and external carotid artery (ICA) for assessment of diameter and velocity, and calculation of flow. The middle cerebral artery (MCA) is assessed via transcranial Doppler ultrasound. Reprinted with permission (203).
Figure 6. Figure 6. Near infrared spectroscopy (NIRS)‐derived cerebral oxygen saturation, deoxy‐hemoglobin (dHb), and oxy‐hemoglobin (HbO2) responses to progressive hemorrhage in humans up to 470 mL (approx. 12% blood loss). Adapted from (236) with permission.
Figure 7. Figure 7. Representative hemodynamic responses to progressive central hypovolemia elicited via application of lower body negative pressure (LBNP) to −60 mmHg in a human subject. As stroke volume (SV) falls progressively, heart rate (HR) and total peripheral resistance (not shown) increase via a baroreflex‐mediated mechanism; mean arterial pressure (MAP) is maintained near baseline levels. At presyncope (dashed line), SV and MAP are reduced by 71% and 38% from baseline while mean middle cerebral artery velocity (MCAv) and cerebral oxygen saturation (ScO2) fall by 51% and 12%.
Figure 8. Figure 8. Hemodynamic responses to a 25% hemorrhage and central blood volume‐matched lower body negative pressure (LBNP) levels in baboons. dP/dt, index of cardiac contractility. Data are mean ± SD. Reprinted with permission (102).
Figure 9. Figure 9. Comparison of stroke volume reductions during lower body negative pressure (LBNP) to a chamber pressure of −45 mmHg, and 1000 mL blood loss (BL) in human subjects. Reprinted with permission (114).
Figure 10. Figure 10. Individual plots of mean arterial pressure (MAP) versus mean middle cerebral artery velocity (MCAv) for all 9 subjects for LBNP (blue circles) and blood loss (red circles). Group responses are presented in the lower right panel (N = 9). Reprinted with permission (19).
Figure 11. Figure 11. Representative tracings of end‐tidal CO2 (etCO2), mean arterial pressure (MAP), and mean middle cerebral artery velocity (MCAv) in one high tolerant (HT) subject (A) and one low tolerant (LT) subject (B) during the final 3 min of presyncopal limited lower body negative pressure (LBNP). Note that respiration rate measured from the etCO2 waveform was ∼14.3 breaths/min (0.24 Hz) for the HT subject and ∼13.3 breaths/min (0.22 Hz) for the LT subject. Reprinted with permission (192).
Figure 12. Figure 12. Low‐frequency (LF) oscillations in mean arterial pressure (MAP) and mean middle cerebral artery velocity (MCAv) during progressive lower body negative pressure (LBNP) up to −60 mmHg (A and C), and at presyncope (B and D) in high tolerant (HT) and low tolerant (LT) subjects. * P ≤ 0.001, between HT and LT. Reprinted with permission (192).
Figure 13. Figure 13. The classic cerebral autoregulation curve demonstrating a cerebral blood flow (CBF) plateau across a range of mean arterial pressures. Three hundred seventy‐six individual data points from 11 groups of subjects and 7 different studies are included. Note the limitations of this original representation of the cerebral autoregulatory plateau in the text (see Cerebral Autoregulation section). Redrawn with permission (134).
Figure 14. Figure 14. Cerebral blood velocity (A), and cerebrovascular resistance (CVR) and conductance (CVC) responses (B) in the middle cerebral artery (MCAv) to step‐wise hypotension induced with sodium nitroprusside and hypertension induced by phenylephrine in human subjects. MAP, mean arterial pressure. Reprinted with permission (144).
Figure 15. Figure 15. Arterial pressure‐cerebral blood velocity (flow) relationship at 0.03 Hz oscillatory lower body negative pressure (OLBNP) suggesting a very narrow autoregulatory “plateau” region within 5 mmHg of baseline. Reprinted with permission (91).
Figure 16. Figure 16. The traditional (green) versus contemporary interpretation of cerebral autoregulation (CA) where intact CA may be represented by a pressure passive response of cerebral blood flow (blue) within certain limits of perfusion pressure (a and b), which then increases (red) as CA becomes impaired. The gain of the pressure‐flow relationship may increase outside of these limits.
Figure 17. Figure 17. Cortical blood‐flow (CBF) responses to reductions in mean arterial pressure (MAP) during progressive hemorrhage in cats. CBF becomes pressure passive between 60 and 69 mmHg MAP, but maximal arterial dilation did not occur until 30 and 39 mmHg MAP. Redrawn with permission (146).
Figure 18. Figure 18. Decreasing arterial pressure progressively reduces cerebrovascular reactivity to the partial pressure of arterial carbon dioxide (PaCO2). Reprinted with permission (94); redrawn by Willie et al. (266).
Figure 19. Figure 19. α‐Adrenergic stimulation of perivascular sympathetic nerves, as would occur during hemorrhage, shifts the cerebral autoregulatory curve to the right, resulting in pressure‐passive responses of cerebral blood flow at higher arterial pressures. Redrawn with permission (177).
Figure 20. Figure 20. The cerebral autoregulatory response to hyper‐ and hypocapnia. Hypercapnia increases cerebral blood flow and narrows the effective range of autoregulation, while hypocapnia decreases cerebral blood flow and widens this range. Redrawn with permission (177).
Figure 21. Figure 21. Two potential responses of the cerebral autoregulatory curve with progressive hypotension to presyncope; a rightward shift due to sympathetic activation (A), or a downward shift, likely due to hypocapnia (B). The “threshold of presyncope” represents the level of cerebral blood flow at which presyncope occurs. With progressive hypocapnia, this threshold would be reached even without changes in arterial pressure. CPP, cerebral perfusion pressure (mean arterial minus intracranial pressure). Reprinted with permission (28).
Figure 22. Figure 22. Sympathetic nerve activity (SNA) in the superior cervical ganglion in responses to increasing and decreasing mean arterial pressure (MAP). There is no change in SNA with decreases in MAP to 48% below baseline. Reprinted with permission (36).
Figure 23. Figure 23. Cerebral blood‐flow responses to blood loss are primarily via changes in oxygen delivery (DO2) and arterial carbon dioxide tension (PaCO2), and subsequent chemoreflex‐mediated alterations in ventilation. Increases in PaCO2 elicit cerebral vasodilation and increases in cerebral blood flow, while decreases in PaCO2 cause cerebral vasoconstriction and decreases in cerebral blood flow. Major blood loss (>50%) must occur to elicit any physiologically relevant decrease in arterial oxygen tension (PaO2), and PaO2 must fall to at least 60 mmHg to stimulate an increase in cerebral blood flow. TBV, total blood volume; ECF, extracellular fluid; CSF, cerebrospinal fluid; CBF, cerebral blood flow; H+, hydrogen ions.
Figure 24. Figure 24. Cerebral blood flow (Q) and cerebral blood velocity (CBV) responses to steady state increases and decreases in arterial carbon dioxide (CO2) and oxygen (O2) in the anterior and posterior cerebral circulations. Blood flow was measured in the internal carotid artery (ICA; anterior circulation) and vertebral artery (VA; posterior circulation), and CBV was measured in the middle cerebral artery (MCA; anterior circulation) and posterior cerebral artery (PCA; posterior circulation). * denotes P < 0.05 from baseline (40 mmHg PaCO2 or 100 mmHg PO2); † denotes P < 0.012 between vessel flow (ICA vs. VA) or velocity (MCA vs. PCA) at a given stage. All values are means ± SD. Reprinted with permission (264).
Figure 25. Figure 25. Cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) responses to progressively decreasing perfusion pressure, as would occur with hemorrhage. A reduction in perfusion pressure elicits vasodilation to maintain CBF up to a threshold (A). Below this threshold, CBF falls, but OEF increases to maintain tissue oxygenation and metabolism (CMRO2). Once oxygen extraction is exhausted (B), CMRO2 decreases, compromising neural function. Redrawn with permission (186).
Figure 26. Figure 26. Cerebral blood flow and oxygenation responses to fluid resuscitation with crystalloid (40 mL/kg) + colloid (20 mL/kg) (FR), hypertonic starch solution (4 mL/kg) plus norepinephrine (NA/HS), or hypertonic starch solution (4 mL/kg) plus arginine vasopressin (AVP/HS) following hemorrhage to MAP of <25 mmHg. BL T: baseline trauma; Th: before start of therapy, and following therapy after 5‐min (Th + 5), 30‐min (Th + 30), and 60‐min (Th + 60); P btO2: brain tissue partial pressure of O2; TOI: tissue oxygenation index; CPP: cerebral perfusion pressure; FV: flow velocity in middle cerebral artery. Values are mean ± SEM. *, denotes P < 0.001 versus BL T for all groups; †, denotes P < 0.001 versus FR; ‡, denotes P < 0.05 versus FR; §, denotes P < 0.01 versus NA/HS. Reprinted with permission (37).


Figure 1. Hemodynamic responses to a 1020 mL hemorrhage in a healthy human subject. Right auricular pressure (RAP) and cardiac output (CO) fall progressively, while heart rate (HR) and total peripheral resistance (TPR) increase via a baroreflex‐mediated mechanism. Blood pressure (BP) is maintained until HR and TPR fall precipitously at the onset of syncope (faint). Redrawn from (18) with permission from Elsevier.


Figure 2. Physiological factors affecting cerebral blood flow during hemorrhage. The ultimate response of cerebral blood flow depends upon the strength and magnitude of each stimulus independently, and the combined interrelationship between all factors.


Figure 3.

(A) The major extracranial vessels supplying the Circle of Willis include the left and right internal carotid arteries (ICA), and the left and right vertebral arteries (VA) fusing to form the basilar artery (BA). The ICAs feed the middle cerebral arteries (MCA) and anterior cerebral arteries (ACA), and the BA feeds the posterior cerebral arteries (PCA). Reprinted with permission (58).

(B) The major intracranial vessels form the Circle of Willis. ACA, anterior cerebral artery; AComA, anterior communicating artery; MCA, middle cerebral artery; ICA, internal carotid artery; PCA, posterior cerebral artery; PComA, posterior communicating artery; SCA, superior cerebellar artery; Basilar A, basilar artery. Reprinted with permission (56).



Figure 4. Summary of findings from four studies assessing changes in middle cerebral artery diameter (MCA) with perturbations in arterial CO2 using MRI technology. These studies indicate that there may be a threshold level of hypo‐ and hypercapnia that induces changes in MCA diameter (between 7% and 10% from baseline). Reprinted with permission (8).


Figure 5. Duplex‐Doppler ultrasound images in a human subject of the vertebral artery (VA), basilar artery (BA), internal carotid artery (ICA), and external carotid artery (ICA) for assessment of diameter and velocity, and calculation of flow. The middle cerebral artery (MCA) is assessed via transcranial Doppler ultrasound. Reprinted with permission (203).


Figure 6. Near infrared spectroscopy (NIRS)‐derived cerebral oxygen saturation, deoxy‐hemoglobin (dHb), and oxy‐hemoglobin (HbO2) responses to progressive hemorrhage in humans up to 470 mL (approx. 12% blood loss). Adapted from (236) with permission.


Figure 7. Representative hemodynamic responses to progressive central hypovolemia elicited via application of lower body negative pressure (LBNP) to −60 mmHg in a human subject. As stroke volume (SV) falls progressively, heart rate (HR) and total peripheral resistance (not shown) increase via a baroreflex‐mediated mechanism; mean arterial pressure (MAP) is maintained near baseline levels. At presyncope (dashed line), SV and MAP are reduced by 71% and 38% from baseline while mean middle cerebral artery velocity (MCAv) and cerebral oxygen saturation (ScO2) fall by 51% and 12%.


Figure 8. Hemodynamic responses to a 25% hemorrhage and central blood volume‐matched lower body negative pressure (LBNP) levels in baboons. dP/dt, index of cardiac contractility. Data are mean ± SD. Reprinted with permission (102).


Figure 9. Comparison of stroke volume reductions during lower body negative pressure (LBNP) to a chamber pressure of −45 mmHg, and 1000 mL blood loss (BL) in human subjects. Reprinted with permission (114).


Figure 10. Individual plots of mean arterial pressure (MAP) versus mean middle cerebral artery velocity (MCAv) for all 9 subjects for LBNP (blue circles) and blood loss (red circles). Group responses are presented in the lower right panel (N = 9). Reprinted with permission (19).


Figure 11. Representative tracings of end‐tidal CO2 (etCO2), mean arterial pressure (MAP), and mean middle cerebral artery velocity (MCAv) in one high tolerant (HT) subject (A) and one low tolerant (LT) subject (B) during the final 3 min of presyncopal limited lower body negative pressure (LBNP). Note that respiration rate measured from the etCO2 waveform was ∼14.3 breaths/min (0.24 Hz) for the HT subject and ∼13.3 breaths/min (0.22 Hz) for the LT subject. Reprinted with permission (192).


Figure 12. Low‐frequency (LF) oscillations in mean arterial pressure (MAP) and mean middle cerebral artery velocity (MCAv) during progressive lower body negative pressure (LBNP) up to −60 mmHg (A and C), and at presyncope (B and D) in high tolerant (HT) and low tolerant (LT) subjects. * P ≤ 0.001, between HT and LT. Reprinted with permission (192).


Figure 13. The classic cerebral autoregulation curve demonstrating a cerebral blood flow (CBF) plateau across a range of mean arterial pressures. Three hundred seventy‐six individual data points from 11 groups of subjects and 7 different studies are included. Note the limitations of this original representation of the cerebral autoregulatory plateau in the text (see Cerebral Autoregulation section). Redrawn with permission (134).


Figure 14. Cerebral blood velocity (A), and cerebrovascular resistance (CVR) and conductance (CVC) responses (B) in the middle cerebral artery (MCAv) to step‐wise hypotension induced with sodium nitroprusside and hypertension induced by phenylephrine in human subjects. MAP, mean arterial pressure. Reprinted with permission (144).


Figure 15. Arterial pressure‐cerebral blood velocity (flow) relationship at 0.03 Hz oscillatory lower body negative pressure (OLBNP) suggesting a very narrow autoregulatory “plateau” region within 5 mmHg of baseline. Reprinted with permission (91).


Figure 16. The traditional (green) versus contemporary interpretation of cerebral autoregulation (CA) where intact CA may be represented by a pressure passive response of cerebral blood flow (blue) within certain limits of perfusion pressure (a and b), which then increases (red) as CA becomes impaired. The gain of the pressure‐flow relationship may increase outside of these limits.


Figure 17. Cortical blood‐flow (CBF) responses to reductions in mean arterial pressure (MAP) during progressive hemorrhage in cats. CBF becomes pressure passive between 60 and 69 mmHg MAP, but maximal arterial dilation did not occur until 30 and 39 mmHg MAP. Redrawn with permission (146).


Figure 18. Decreasing arterial pressure progressively reduces cerebrovascular reactivity to the partial pressure of arterial carbon dioxide (PaCO2). Reprinted with permission (94); redrawn by Willie et al. (266).


Figure 19. α‐Adrenergic stimulation of perivascular sympathetic nerves, as would occur during hemorrhage, shifts the cerebral autoregulatory curve to the right, resulting in pressure‐passive responses of cerebral blood flow at higher arterial pressures. Redrawn with permission (177).


Figure 20. The cerebral autoregulatory response to hyper‐ and hypocapnia. Hypercapnia increases cerebral blood flow and narrows the effective range of autoregulation, while hypocapnia decreases cerebral blood flow and widens this range. Redrawn with permission (177).


Figure 21. Two potential responses of the cerebral autoregulatory curve with progressive hypotension to presyncope; a rightward shift due to sympathetic activation (A), or a downward shift, likely due to hypocapnia (B). The “threshold of presyncope” represents the level of cerebral blood flow at which presyncope occurs. With progressive hypocapnia, this threshold would be reached even without changes in arterial pressure. CPP, cerebral perfusion pressure (mean arterial minus intracranial pressure). Reprinted with permission (28).


Figure 22. Sympathetic nerve activity (SNA) in the superior cervical ganglion in responses to increasing and decreasing mean arterial pressure (MAP). There is no change in SNA with decreases in MAP to 48% below baseline. Reprinted with permission (36).


Figure 23. Cerebral blood‐flow responses to blood loss are primarily via changes in oxygen delivery (DO2) and arterial carbon dioxide tension (PaCO2), and subsequent chemoreflex‐mediated alterations in ventilation. Increases in PaCO2 elicit cerebral vasodilation and increases in cerebral blood flow, while decreases in PaCO2 cause cerebral vasoconstriction and decreases in cerebral blood flow. Major blood loss (>50%) must occur to elicit any physiologically relevant decrease in arterial oxygen tension (PaO2), and PaO2 must fall to at least 60 mmHg to stimulate an increase in cerebral blood flow. TBV, total blood volume; ECF, extracellular fluid; CSF, cerebrospinal fluid; CBF, cerebral blood flow; H+, hydrogen ions.


Figure 24. Cerebral blood flow (Q) and cerebral blood velocity (CBV) responses to steady state increases and decreases in arterial carbon dioxide (CO2) and oxygen (O2) in the anterior and posterior cerebral circulations. Blood flow was measured in the internal carotid artery (ICA; anterior circulation) and vertebral artery (VA; posterior circulation), and CBV was measured in the middle cerebral artery (MCA; anterior circulation) and posterior cerebral artery (PCA; posterior circulation). * denotes P < 0.05 from baseline (40 mmHg PaCO2 or 100 mmHg PO2); † denotes P < 0.012 between vessel flow (ICA vs. VA) or velocity (MCA vs. PCA) at a given stage. All values are means ± SD. Reprinted with permission (264).


Figure 25. Cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) responses to progressively decreasing perfusion pressure, as would occur with hemorrhage. A reduction in perfusion pressure elicits vasodilation to maintain CBF up to a threshold (A). Below this threshold, CBF falls, but OEF increases to maintain tissue oxygenation and metabolism (CMRO2). Once oxygen extraction is exhausted (B), CMRO2 decreases, compromising neural function. Redrawn with permission (186).


Figure 26. Cerebral blood flow and oxygenation responses to fluid resuscitation with crystalloid (40 mL/kg) + colloid (20 mL/kg) (FR), hypertonic starch solution (4 mL/kg) plus norepinephrine (NA/HS), or hypertonic starch solution (4 mL/kg) plus arginine vasopressin (AVP/HS) following hemorrhage to MAP of <25 mmHg. BL T: baseline trauma; Th: before start of therapy, and following therapy after 5‐min (Th + 5), 30‐min (Th + 30), and 60‐min (Th + 60); P btO2: brain tissue partial pressure of O2; TOI: tissue oxygenation index; CPP: cerebral perfusion pressure; FV: flow velocity in middle cerebral artery. Values are mean ± SEM. *, denotes P < 0.001 versus BL T for all groups; †, denotes P < 0.001 versus FR; ‡, denotes P < 0.05 versus FR; §, denotes P < 0.01 versus NA/HS. Reprinted with permission (37).
References
 1. Aaslid R . Visually evoked dynamic blood flow response of the human cerebral circulation. Stroke 18: 771‐775, 1987.
 2. Aaslid R . Developments and principles of transcranial Doppler. In: Newell DW , Aaslid R , editors. Transcranial Doppler. New York, NY: Raven Press, 1992, pp. 1‐8.
 3. Aaslid R , Markwalder TM , Nornes H . Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 57: 769‐774, 1982.
 4. Abbott NJ , Patabendige AA , Dolman DE , Yusof SR , Begley DJ . Structure and function of the blood‐brain barrier. Neurobiol Dis 37: 13‐25, 2010.
 5. Adams JA , Bassuk J , Wu D , Grana M , Kurlansky P , Sackner MA . Periodic acceleration: Effects on vasoactive, fibrinolytic, and coagulation factors. J Appl Physiol 98: 1083‐1090, 2005.
 6. Ainslie PN , Burgess KR . Cardiorespiratory and cerebrovascular responses to hyperoxic and hypoxic rebreathing: Effects of acclimatization to high altitude. Respir Physiol Neurobiol 161: 201‐209, 2008.
 7. Ainslie PN , Duffin J . Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: Mechanisms of regulation, measurement, and interpretation. Am J Physiol Regul Integr Comp Physiol 296: R1473‐1495, 2009.
 8. Ainslie PN , Hoiland RL . Transcranial Doppler ultrasound: Valid, invalid, or both? J Appl Physiol 117: 1081‐1083, 2014.
 9. Ainslie PN , Ogoh S . Regulation of cerebral blood flow in mammals during chronic hypoxia: A matter of balance. Exp Physiol 95: 251‐262, 2010.
 10. Akabori H , Moeinpour F , Bland KI , Chaudry IH . Mechanism of the anti‐inflammatory effect Of 17beta‐estradiol on brain following trauma‐hemorrhage. Shock 33: 43‐48, 2010.
 11. Al‐Rawi PG , Kirkpatrick PJ . Tissue oxygen index: Thresholds for cerebral ischemia using near‐infrared spectroscopy. Stroke 37: 2720‐2725, 2006.
 12. Albeck MJ , Borgesen SE , Gjerris F , Schmidt JF , Sorensen PS . Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects. J Neurosurg 74: 597‐600, 1991.
 13. Allen BS , Ko Y , Buckberg GD , Tan Z . Studies of isolated global brain ischaemia: III. Influence of pulsatile flow during cerebral perfusion and its link to consistent full neurological recovery with controlled reperfusion following 30 min of global brain ischaemia. Eur J Cardiothorac Surg 41: 1155‐1163, 2012.
 14. Andrews PJD , Dearden NM , Miller JD . Jugular bulb cannulation: Description of a cannulation technique and validation of a new continuous monitor. Br J Anaesth 67: 553‐558, 1991.
 15. Angele MK , Schwacha MG , Ayala A , Chaudry IH . Effect of gender and sex hormones on immune responses following shock. Shock 14: 81‐90, 2000.
 16. Aukland K , Bower BF , Berliner RW . Measurement of local blood flow with hydrogen gas. Circ Res 14: 164‐187, 1964.
 17. Ballabh P , Braun A , Nedergaard M . The blood‐brain barrier: An overview: Structure, regulation, and clinical implications. Neurobiol Dis 16: 1‐13, 2004.
 18. Barcroft H , Edholm OG , McMichael J , Sharpey‐Schafer EP . Posthaemorrhagic fainting study by cardiac output and forearm flow. Lancet i: 489‐491, 1944.
 19. Barnes JN , Schmidt JE , Nicholson WT , Joyner MJ . Cyclooxygenase inhibition abolishes age‐related differences in cerebral vasodilator responses to hypercapnia. J Appl Physiol 112: 1884‐1890, 2012.
 20. Bartels E . Transcranial color‐coded duplex ultrasonography in routine cerebrovascular diagnostics. Perspect Med 1: 325‐330, 2012.
 21. Bassin R , Vladeck BC , Kark AE , Shoemaker WC . Rapid and slow hemorrhage in man. I. Sequential hemodynamic responses. Ann Surg 173: 325‐330, 1971.
 22. Bassuk JI , Wu H , Arias J , Kurlansky P , Adams JA . Whole body periodic acceleration (pGz) improves survival and allows for resuscitation in a model of severe hemorrhagic shock in pigs. J Surg Res 164: e281‐289, 2010.
 23. Battisti‐Charbonney A , Fisher J , Duffin J . The cerebrovascular response to carbon dioxide in humans. J Physiol 589: 3039‐3048, 2011.
 24. Becker LB , Weisfeldt ML , Weil MH , Budinger T , Carrico J , Kern K , Nichol G , Shechter I , Traystman R , Webb C , Wiedemann H , Wise R , Sopko G . The PULSE initiative: Scientific priorities and strategic planning for resuscitation research and life saving therapies. Circulation 105: 2562‐2570, 2002.
 25. Bill A , Linder J . Sympathetic control of cerebral blood flow in acute arterial hypertension. Acta Physiol Scand 96: 114‐121, 1976.
 26. Bolliger D , Gorlinger K , Tanaka KA . Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. Anesthesiology 113: 1205‐1219, 2010.
 27. Bondar RL , Kassam MS , Stein F , Dunphy PT , Fortney S , Riedesel ML . Simultaneous cerebrovascular and cardiovascular responses during presyncope. Stroke 26: 1794‐1800, 1995.
 28. Bronshvag MM . Cerebral pathophysiology in hemorrhagic shock. Nuclide scan data, fluorescence microscopy, and anatomic correlations. Stroke 11: 50‐59, 1980.
 29. Brown AM , Ransom BR . Astrocyte glycogen and brain energy metabolism. Glia 55: 1263‐1271, 2007.
 30. Brown AM , Ransom BR . Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity. Metab Brain Dis 30: 233‐239, 2015.
 31. Brown CM , Dutsch M , Hecht MJ , Neundorfer B , Hilz MJ . Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation. J Neurol Sci 208: 71‐78, 2003.
 32. Brown TE , Beightol LA , Koh J , Eckberg DL . Important influence of respiration on human R‐R interval power spectra is largely ignored. J Appl Physiol 75: 2310‐2317, 1993.
 33. Busija DW , Heistad DD . Factors involved in the physiological regulation of the cerebral circulation. Rev Physiol Biochem Pharmacol 101: 161‐211, 1984.
 34. Buunk G , van der Hoeven JG , Meinders AE . A comparison of near‐infrared spectroscopy and jugular bulb oximetry in comatose patients resuscitated from a cardiac arrest. Anaesthesia 53: 13‐19, 1998.
 35. Cassaglia PA , Griffiths RI , Walker AM . Sympathetic nerve activity in the superior cervical ganglia increases in response to imposed increases in arterial pressure. Am J Physiol Regul Integr Comp Physiol 294: R1255‐1261, 2008.
 36. Cavus E , Meybohm P , Doerges V , Hugo HH , Steinfath M , Nordstroem J , Scholz J , Bein B . Cerebral effects of three resuscitation protocols in uncontrolled haemorrhagic shock: A randomised controlled experimental study. Resuscitation 80: 567‐572, 2009.
 37. Cavus E , Meybohm P , Dorges V , Stadlbauer KH , Wenzel V , Weiss H , Scholz J , Bein B . Regional and local brain oxygenation during hemorrhagic shock: A prospective experimental study on the effects of small‐volume resuscitation with norepinephrine. J Trauma 64: 641‐648; discussion 648‐649, 2008.
 38. Chapman RW , Santiago TV , Edelman NH . Effects of graded reduction of brain blood flow on chemical control of breathing. J Appl Physiol 47: 1289‐1294, 1979.
 39. Chapman RW , Santiago TV , Edelman NH . Effects of graded reduction of brain blood flow on ventilation in unanesthetized goats. J Appl Physiol 47: 104‐111, 1979.
 40. Chen RY , Fan FC , Schuessler GB , Simchon S , Kim S , Chien S . Regional cerebral blood flow and oxygen consumption of the canine brain during hemorrhagic hypotension. Stroke 15: 343‐350, 1984.
 41. Chien S . Role of the sympathetic nervous system in hemorrhage. Physiol Rev 47: 214‐288, 1967.
 42. Cohen PJ , Alexander SC , Smith TC , Reivich M , Wollman H . Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man. J Appl Physiol 23: 183‐189, 1967.
 43. Colier WN , Binkhorst RA , Hopman MT , Oeseburg B . Cerebral and circulatory haemodynamics before vasovagal syncope induced by orthostatic stress. Clin Physiol 17: 83‐94, 1997.
 44. Convertino VA , Parquette B , Zeihr J , Traynor K , Baia D , Baumblatt M , Vartanian L , Suresh M , Metzger A , Gerhardt RT , Lurie KG , Lindstrom D . Use of respiratory impedance in prehospital care of hypotensive patients associated with hemorrhage and trauma: A case series. J Trauma Acute Care Surg 73: S54‐59, 2012.
 45. Convertino VA , Rickards CA , Lurie KG , Ryan KL . Hyperventilation in response to progressive reduction in central blood volume to near syncope. Aviat Space Environ Med 80: 1012‐1017, 2009.
 46. Convertino VA , Ryan KL , Rickards CA , Salinas J , McManus JG , Cooke WH , Holcomb JB . Physiological and medical monitoring for en route care of combat casualties. J Trauma 64: S342‐353, 2008.
 47. Convertino VA , Sather TM . Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans. Clin Physiol 20: 177‐184, 2000.
 48. Cooke WH , Cox JF , Diedrich AM , Taylor JA , Beightol LA , Ames JE , Hoag JB , Seidel H , Eckberg DL . Controlled breathing protocols probe human autonomic cardiovascular rhythms. Am J Physiol 274: H709‐718, 1998.
 49. Cooke WH , Rickards CA , Ryan KL , Kuusela TA , Convertino VA . Muscle sympathetic nerve activity during intense lower body negative pressure to presyncope in humans. J Physiol 587: 4987‐4999, 2009.
 50. Cooke WH , Ryan KL , Convertino VA . Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans. J Appl Physiol 96: 1249‐1261, 2004.
 51. Coverdale NS , Gati JS , Opalevych O , Perrotta A , Shoemaker JK . Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia. J Appl Physiol 117: 1090‐1096, 2014.
 52. Czosnyka M , Guazzo E , Iyer V , Kirkpatrick P , Smielewski P , Whitehouse H , Pickard JD . Testing of cerebral autoregulation in head injury by waveform analysis of blood flow velocity and cerebral perfusion pressure. Acta Neurochir Suppl (Wien) 60: 468‐471, 1994.
 53. Dalsgaard MK , Madsen FF , Secher NH , Laursen H , Quistorff B . High glycogen levels in the hippocampus of patients with epilepsy. J Cereb Blood Flow Metab 27: 1137‐1141, 2007.
 54. Davie SN , Grocott HP . Impact of extracranial contamination on regional cerebral oxygen saturation: A comparison of three cerebral oximetry technologies. Anesthesiology 116: 834‐840, 2012.
 55. Day AL . Arterial distributions and variants. In: Wood JH , editor. Cerebral Blood Flow: Physiologic and Clinical Aspects. New York, NY: McGraw Hill Book Company, 1987, pp. 19‐36.
 56. Doepp F , Schreiber SJ , von Munster T , Rademacher J , Klingebiel R , Valdueza JM . How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns. Neuroradiology 46: 565‐570, 2004.
 57. Drake RL , Vogl AW , Mitchell AWM . Head and Neck. In: Drake RL , Vogl AW , Mitchell AWM , editors. Gray's Anatomy for Students. Philadelphia, PA: Churchill Livingstone, 2015, pp. 835‐1135.
 58. Duschek S , Schandry R . Reduced brain perfusion and cognitive performance due to constitutional hypotension. Clin Auton Res 17: 69‐76, 2007.
 59. Eastridge BJ , Mabry RL , Seguin P , Cantrell J , Tops T , Uribe P , Mallett O , Zubko T , Oetjen‐Gerdes L , Rasmussen TE , Butler FK , Kotwal RS , Holcomb JB , Wade C , Champion H , Lawnick M , Moores L , Blackbourne LH . Death on the battlefield (2001‐2011): Implications for the future of combat casualty care. J Trauma Acute Care Surg 73: S431‐437, 2012.
 60. Fan JL , Burgess KR , Basnyat R , Thomas KN , Peebles KC , Lucas SJ , Lucas RA , Donnelly J , Cotter JD , Ainslie PN . Influence of high altitude on cerebrovascular and ventilatory responsiveness to CO2. J Physiol 588: 539‐549, 2010.
 61. Fitch W , MacKenzie ET , Harper AM . Effects of decreasing arterial blood pressure on cerebral blood flow in the baboon. Influence of the sympathetic nervous system. Circ Res 37: 550‐557, 1975.
 62. Flaherty DC , Hoxha B , Sun J , Gurji H , Simecka JW , Mallet RT , Olivencia‐Yurvati AH . Pyruvate‐fortified fluid resuscitation improves hemodynamic stability while suppressing systemic inflammation and myocardial oxidative stress after hemorrhagic shock. Mil Med 175: 166‐172, 2010.
 63. Fog M . Cerebral circulation: I. reaction of pial arteries to epinephrine by direct application and by intravenous injection. Arch Neurol Psychiatry 41: 109‐118, 1939.
 64. Fog M . Cerebral circulation: II. reaction of pial arteries to increase in blood pressure. Arch Neurol Psychiatry 41: 260‐268, 1939.
 65. Forbes HS , Cobb SS . Vasomotor control of cerebral vessels. Brain 61: 221‐232, 1938.
 66. Forsyth RP , Hoffbrand BI , Melmon KL . Redistribution of cardiac output during hemorrhage in the unanesthetized monkey. Circ Res 27: 311‐320, 1970.
 67. Fregosi RF . Changes in the neural drive to abdominal expiratory muscles in hemorrhagic hypotension. Am J Physiol 266: H2423‐2429, 1994.
 68. Fujioka KA , Douville CM . Anatomy and freehand examination techniques. In: Newell DW , Aaslid R , editors. Transcranial Doppler. New York: Raven Press, 1992, pp. 9‐32.
 69. Gadda G , Taibi A , Sisini F , Gambaccini M , Zamboni P , Ursino M . A new hemodynamic model for the study of cerebral venous outflow. Am J Physiol Heart Circ Physiol 308: H217‐H231, 2015.
 70. Garrioch MA . The body's response to blood loss. Vox Sang 87(Suppl. 1): 74‐76, 2004.
 71. Germon TJ , Evans PD , Barnett NJ , Wall P , Manara AR , Nelson RJ . Cerebral near infrared spectroscopy: Emitter‐detector separation must be increased. Br J Anaesth 82: 831‐837, 1999.
 72. Germon TJ , Kane NM , Manara AR , Nelson RJ . Near‐infrared spectroscopy in adults: Effects of extracranial ischaemia and intracranial hypoxia on estimation of cerebral oxygenation. Br J Anaesth 73: 503‐506, 1994.
 73. Gernandt B , Liljestrand G , Zotterman Y . Efferent impulses in the splanchnic nerve. Acta Physiol Scand 11: 231‐247, 1946.
 74. Giller CA . The frequency‐dependent behaviours of cerebral autoregulation. Neurosurgery 27: 362‐368, 1990.
 75. Giller CA . The Emperor has no clothes: Velocity, flow, and the use of TCD. J Neuroimaging 13: 97‐98, 2003.
 76. Giller CA , Bowman G , Dyer H , Mootz L , Krippner W . Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. Neurosurgery 32: 737‐742, 1993.
 77. Giller CA , Levine BD , Meyer Y , Buckey JC , Lane LD , Borchers DJ . The cerebral hemodynamics of normotensive hypovolemia during lower‐body negative pressure. J Neurosurg 76: 961‐966, 1992.
 78. Gisolf J , van Lieshout JJ , van Heusden K , Pott F , Stok WJ , Karemaker JM . Human cerebral venous outflow pathway depends on posture and central venous pressure. J Physiol 560: 317‐327, 2004.
 79. Glaister DH , Miller NL . Cerebral tissue oxygen status and psychomotor performance during lower body negative pressure (LBNP). Aviat Space Environ Med 61: 99‐105, 1990.
 80. Golanov EV , Christensen JR , Reis DJ . Neurons of a limited subthalamic area mediate elevations in cortical cerebral blood flow evoked by hypoxia and excitation of neurons of the rostral ventrolateral medulla. J Neurosci 21: 4032‐4041, 2001.
 81. Gootman PM , Cohen MI . Efferent splanchnic activity and systemic arterial pressure. Am J Physiol 219: 897‐903, 1970.
 82. Graham DI , Fitch W , MacKenzie ET , Harper AM . Effects of hemorrhagic hypotension on the cerebral circulation. III. Neuropathology. Stroke 10: 724‐727, 1979.
 83. Greenleaf JE , Petersen TW , Gabrielsen A , Pump B , Bie P , Christensen NJ , Warberg J , Videbaek R , Simonson SR , Norsk P . Low LBNP tolerance in men is associated with attenuated activation of the renin‐angiotensin system. Am J Physiol 279: R822‐829, 2000.
 84. Gregory PC , McGeorge AP , Fitch W , Graham DI , MacKenzie ET , Harper AM . Effects of hemorrhagic hypotension on the cerebral circulation. II. Electrocortical function. Stroke 10: 719‐723, 1979.
 85. Guerci AD , Shi AY , Levin H , Tsitlik J , Weisfeldt ML , Chandra N . Transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation in dogs. Circ Res 56: 20‐30, 1985.
 86. Guo H , Tierney N , Schaller F , Raven PB , Smith SA , Shi X . Cerebral autoregulation is preserved during orthostatic stress superimposed with systemic hypotension. J Appl Physiol 100: 1785‐1792, 2006.
 87. Gutierrez G , Reines HD , Wulf‐Gutierrez ME . Clinical review: Hemorrhagic shock. Crit Care 8: 373‐381, 2004.
 88. Hajjar I , Hart M , Chen YL , Mack W , Novak V , Chui CH , Lipsitz L . Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: Results of a pilot randomized clinical trial. J Am Geriatr Soc 61: 194‐201, 2013.
 89. Hamner JW , Cohen MA , Mukai S , Lipsitz LA , Taylor JA . Spectral indices of human cerebral blood flow control: Responses to augmented blood pressure oscillations. J Physiol 559: 965‐973, 2004.
 90. Hamner JW , Tan CO . Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation. Stroke 45: 1771‐1777, 2014.
 91. Hamner JW , Tan CO , Lee K , Cohen MA , Taylor JA . Sympathetic control of the cerebral vasculature in humans. Stroke 41: 102‐109, 2010.
 92. Hamner JW , Tan CO , Tzeng YC , Taylor JA . Cholinergic control of the cerebral vasculature in humans. J Physiol 590: 6343‐6352, 2012.
 93. Harper AM , Glass HI . Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. J Neurol Neurosurg Psychiatry 28: 449‐452, 1965.
 94. Hayter MA , Pavenski K , Baker J . Massive transfusion in the trauma patient: Continuing Professional Development. Can J Anaesth 59: 1130‐1145, 2012.
 95. Heistad D , Abboud FM , Mark AL , Schmid PG . Effect of baroreceptor activity on ventilatory response to chemoreceptor stimulation. J Appl Physiol 39: 411‐416, 1975.
 96. Heistad DD , Abboud FM . Dickinson W. Richards Lecture: Circulatory adjustments to hypoxia. Circulation 61: 463‐470, 1980.
 97. Heistad DD , Abboud FM , Mark AL , Schmid PG . Interaction of baroreceptor and chemoreceptor reflexes. Modulation of the chemoreceptor reflex by changes in baroreceptor activity. J Clin Invest 53: 1226‐1236, 1974.
 98. Heistad DD , Kontos HA . Cerebral Circulation. In: Shepherd JT , Abboud FM , Geiger SR , editors. Handbook of Physiology, Section 2. Bethesda: American Physiological Society, 1983, pp. 137‐182.
 99. Heistad DD , Marcus ML . Evidence that neural mechanisms do not have important effects on cerebral blood flow. Circ Res 42: 295‐302, 1978.
 100. Heistad DD , Marcus ML , Abboud FM . Role of large arteries in regulation of cerebral blood flow in dogs. J Clin Invest 62: 761‐768, 1978.
 101. Hinojosa‐Laborde C , Shade RE , Muniz GW , Bauer C , Goei KA , Pidcoke HF , Chung KK , Cap AP , Convertino VA . Validation of lower body negative pressure as an experimental model of hemorrhage. J Appl Physiol 116: 406‐415, 2014.
 102. Hirasawa A , Yanagisawa S , Tanaka N , Funane T , Kiguchi M , Sorensen H , Secher NH , Ogoh S . Influence of skin blood flow and source‐detector distance on near‐infrared spectroscopy‐determined cerebral oxygenation in humans. Clin Physiol Funct Imaging (in press), 2014.
 103. Hoedt‐Rasmussen K , Sveinsdottir E , Lassen NA . Regional cerebral blood flow in man determined by intra‐arterial injection of radioactive inert gas. Circ Res 18: 237‐247, 1966.
 104. Houtman S , Serrador JM , Colier WN , Strijbos DW , Shoemaker K , Hopman MT . Changes in cerebral oxygenation and blood flow during LBNP in spinal cord‐injured individuals. J Appl Physiol 91: 2199‐2204, 2001.
 105. Huang SY , Moore LG , McCullough RE , McCullough RG , Micco AJ , Fulco C , Cymerman A , Manco‐Johnson M , Weil JV , Reeves JT . Internal carotid and vertebral arterial flow velocity in men at high altitude. J Appl Physiol 63: 395‐400, 1987.
 106. Ide K , Eliasziw M , Poulin MJ . Relationship between middle cerebral artery blood velocity and end‐tidal PCO2 in the hypocapnic‐hypercapnic range in humans. J Appl Physiol 95: 129‐137, 2003.
 107. Immink RV , Hollmann MW , Truijen J , Kim YS , van Lieshout JJ . The cerebrovascular pressure‐flow relationship: A simple concept but a complex phenomenon. Hypertension 56: e2; author reply e3, 2010.
 108. Imray C , Chan C , Stubbings A , Rhodes H , Patey S , Wilson MH , Bailey DM , Wright AD . Time course variations in the mechanisms by which cerebral oxygen delivery is maintained on exposure to hypoxia/altitude. High Alt Med Biol 15: 21‐27, 2014.
 109. Jacobsen J , Secher NH . Changing concepts of hypovolemic shock. In: Secher NH , Pawelczyk JA , Ludbrook J , editors. Blood Loss and Shock. London, UK: Edward Arnold, 1994, pp. 3‐10.
 110. Jacobsen J , Secher NH . Heart rate during haemorrhagic shock. Clin Physiol 12: 659‐666, 1992.
 111. Jacobsen J , Sofelt S , Sheikh S , Warberg J , Secher NH . Cardiovascular and endocrine responses to haemorrhage in the pig. Acta Physiol Scand 138: 167‐173, 1990.
 112. Jobsis FF . Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198: 1264‐1267, 1977.
 113. Johnson BD , van Helmond N , Curry TB , van Buskirk CM , Convertino VA , Joyner MJ . Reductions in central venous pressure by lower body negative pressure or blood loss elicit similar hemodynamic responses. J Appl Physiol 117: 131‐141, 2014.
 114. Johnson JM , Rowell LB , Niederberger M , Eisman MM . Human splanchnic and forearm vasoconstrictor responses to reductions of right atrial and aortic pressures. Circ Res 34: 515‐524, 1974.
 115. Jones JV , Fitch W , MacKenzie ET , Strandgaard S , Harper AM . Lower limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res 39: 555‐557, 1976.
 116. Jordan J , Shannon JR , Diedrich A , Black B , Costa F , Robertson D , Biaggioni I . Interaction of carbon dioxide and sympathetic nervous system activity in the regulation of cerebral perfusion in humans. Hypertension 36: 383‐388, 2000.
 117. Julien C . The enigma of Mayer waves: Facts and models. Cardiovasc Res 70: 12‐21, 2006.
 118. Kaihara S , Rutherford RB , Schwentker EP , Wagner HN, Jr . Distribution of cardiac output in experimental hemorrhagic shock in dogs. J Appl Physiol 27: 218‐222, 1969.
 119. Kampf S , Schramm P , Klein KU . Transcranial doppler and near infrared spectroscopy in the perioperative period. Curr Opin Anesthesiol 26: 543‐548, 2013.
 120. Kauvar DS , Holcomb JB , Norris GC , Hess JR . Fresh whole blood transfusion: A controversial military practice. J Trauma 61: 181‐184, 2006.
 121. Kauvar DS , Lefering R , Wade CE . Impact of hemorrhage on trauma outcome: An overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma 60: S3‐11, 2006.
 122. Kety SS , Schmidt CF . The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am J Physiol 143: 53‐66, 1945.
 123. Kety SS , Schmidt CF . The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27: 484‐492, 1948.
 124. Kety SS , Schmidt CF . The nitrous oxide method for the quantitative determination of cerebral blood flow in man: Theory, procedure and normal values. J Clin Invest 27: 476‐483, 1948.
 125. Kim YS , Immink RV , Stok WJ , Karemaker JM , Secher NH , van Lieshout JJ . Dynamic cerebral autoregulatory capacity is affected early in Type 2 diabetes. Clin Sci 115: 255‐262, 2008.
 126. Kimmerly DS , O'Leary DD , Menon RS , Gati JS , Shoemaker JK . Cortical regions associated with autonomic cardiovascular regulation during lower body negative pressure in humans. J Physiol 569: 331‐345, 2005.
 127. Kontos HA . Validity of cerebral arterial blood flow calculations from velocity measurements. Stroke 20: 1‐3, 1989.
 128. Kontos HA , Raper AJ , Patterson JL . Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels. Stroke 8: 358‐360, 1977.
 129. Kontos HA , Wei EP , Raper AJ , Rosenblum WI , Navari RM , Patterson JL, Jr . Role of tissue hypoxia in local regulation of cerebral microcirculation. Am J Physiol 234: H582‐591, 1978.
 130. Koyama S , Aibiki M , Kanai K , Fujita T , Miyakawa K . Role of central nervous system in renal nerve activity during prolonged hemorrhagic shock in dogs. Am J Physiol 254: R761‐769, 1988.
 131. Krause DN , Duckles SP , Pelligrino DA . Influence of sex steroid hormones on cerebrovascular function. J Appl Physiol 101: 1252‐1261, 2006.
 132. Krizbai IA , Lenzser G , Szatmari E , Farkas AE , Wilhelm I , Fekete Z , Erdos B , Bauer H , Bauer HC , Sandor P , Komjati K . Blood‐brain barrier changes during compensated and decompensated hemorrhagic shock. Shock 24: 428‐433, 2005.
 133. Lassen NA . Cerebral blood flow and oxygen consumption in man. Physiol Rev 39: 183‐238, 1959.
 134. Ledgerwood AM , Blaisdell W . Coagulation challenges after severe injury with hemorrhagic shock. J Trauma Acute Care Surg 72: 1714‐1718, 2012.
 135. Levasseur JE , Wei EP , Raper AJ , Kontos AA , Patterson JL . Detailed description of a cranial window technique for acute and chronic experiments. Stroke 6: 308‐317, 1975.
 136. Levine BD , Giller CA , Lane LD , Buckey JC , Blomqvist CG . Cerebral versus systemic hemodynamics during graded orthostatic stress in humans. Circulation 90: 298‐306, 1994.
 137. Levine BD , Zhang R . Comments on Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Autonomic control of the cerebral circulation is most important for dynamic cerebral autoregulation. J Appl Physiol 105: 1369‐1373, 2008.
 138. Lewis NC , Bain AR , MacLeod DB , Wildfong KW , Smith KJ , Willie CK , Sanders ML , Numan T , Morrison SA , Foster GE , Stewart JM , Ainslie PN . Impact of hypocapnia and cerebral perfusion on orthostatic tolerance. J Physiol 592: 5203‐5219, 2014.
 139. Lewis SB , Wong ML , Bannan PE , Piper IR , Reilly PL . Transcranial Doppler assessment of the lower cerebral autoregulatory threshold. J Clin Neurosci 6: 42‐45, 1999.
 140. Lipsitz LA , Mukai S , Hamner J , Gagnon M , Babikian V . Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke 31: 1897‐1903, 2000.
 141. Lucas SJ , Burgess KR , Thomas KN , Donnelly J , Peebles KC , Lucas RA , Fan JL , Cotter JD , Basnyat R , Ainslie PN . Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m. J Physiol 589: 741‐753, 2011.
 142. Lucas SJ , Lewis NC , Sikken EL , Thomas KN , Ainslie PN . Slow breathing as a means to improve orthostatic tolerance: A randomized sham‐controlled trial. J Appl Physiol 115: 202‐211, 2013.
 143. Lucas SJ , Tzeng YC , Galvin SD , Thomas KN , Ogoh S , Ainslie PN . Influence of changes in blood pressure on cerebral perfusion and oxygenation. Hypertension 55: 698‐705, 2010.
 144. Lurie KG , Voelckel WG , Zielinski T , McKnite S , Lindstrom P , Peterson C , Wenzel V , Lindner KH , Samniah N , Benditt D . Improving standard cardiopulmonary resuscitation with an inspiratory impedance threshold valve in a porcine model of cardiac arrest. Anesth Analg 93: 649‐655, 2001.
 145. MacKenzie ET , Farrar JK , Fitch W , Graham DI , Gregory PC , Harper AM . Effects of hemorrhagic hypotension on the cerebral circulation. I. Cerebral blood flow and pial arteriolar caliber. Stroke 10: 711‐718, 1979.
 146. MacKenzie ET , McGeorge AP , Graham DI , Fitch W , Edvinsson L , Harper AM . Effects of increasing arterial pressure on cerebral blood flow in the baboon: Influence of the sympathetic nervous system. Pflugers Arch 378: 189‐195, 1979.
 147. MacKenzie ET , Strandgaard S , Graham DI , Jones JV , Harper AM , Farrar JK . Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood‐brain barrier. Circ Res 39: 33‐41, 1976.
 148. Madsen P , Lyck F , Pedersen M , Olesen HL , Nielsen H , Secher NH . Brain and muscle oxygen saturation during head‐up‐tilt‐induced central hypovolaemia in humans. Clin Physiol 15: 523‐533, 1995.
 149. Madsen P , Pott F , Olsen SB , Nielsen HB , Burcev I , Secher NH . Near‐infrared spectrophotometry determined brain oxygenation during fainting. Acta Physiol Scand 162: 501‐507, 1998.
 150. Madsen PL , Secher NH . Near‐infrared oximetry of the brain. Prog Neurobiol 58: 541‐560, 1999.
 151. Marino BS , Yannopoulos D , Sigurdsson G , Lai L , Cho C , Redington A , Nicolson S , Nadkarni V , Lurie KG . Spontaneous breathing through an inspiratory impedance threshold device augments cardiac index and stroke volume index in a pediatric porcine model of hemorrhagic hypovolemia. Crit Care Med 32: S398‐405, 2004.
 152. Martin PJ , Evans DH , Naylor AR . Measurement of blood flow velocity in the basal cerebral circulation: Advantages of transcranial color‐coded sonography over conventional transcranial Doppler. J Clin Ultrasound 23: 21‐26, 1995.
 153. Martin PJ , Evans DH , Naylor AR . Transcranial color‐coded sonography of the basal cerebral circulation. Reference data from 115 volunteers. Stroke 25: 390‐396, 1994.
 154. Matsuda H , Raju TN , Maeta H , John E , Fornel L , Vidyasagar D . Effect of acute hypovolemic hypotension on cerebral metabolism in newborn piglets. Brain Dev 10: 13‐19, 1988.
 155. McHenry LC, Jr , Fazekas JF , Sullivan JF . Cerebral hemodynamics of syncope. Am J Med Sci 241: 173‐178, 1961.
 156. Meel‐van den Abeelen AS , Simpson DM , Wang LJ , Slump CH , Zhang R , Tarumi T , Rickards CA , Payne S , Mitsis GD , Kostoglou K , Marmarelis V , Shin D , Tzeng YC , Ainslie PN , Gommer E , Muller M , Dorado AC , Smielewski P , Yelicich B , Puppo C , Liu X , Czosnyka M , Wang CY , Novak V , Panerai RB , Claassen JA . Between‐centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure‐flow relation: The CARNet study. Med Eng Phys 36: 620‐627, 2014.
 157. Meno JR , Ngai AC , Winn HR . Changes in pial arteriolar diameter and CSF adenosine concentrations during hypoxia. J Cereb Blood Flow Metab 13: 214‐220, 1993.
 158. Mitchell DA , Lambert G , Secher NH , Raven PB , van Lieshout J , Esler MD . Jugular venous overflow of noradrenaline from the brain: A neurochemical indicator of cerebrovascular sympathetic nerve activity in humans. J Physiol 587: 2589‐2597, 2009.
 159. Murray RH , Thompson LJ , Bowers JA , Albright CD . Hemodynamic effects of graded hypovolemia and vasodepressor syncope induced by lower body negative pressure. Am Heart J 76: 799‐811, 1968.
 160. Musgrave FS , Zechman FW , Mains RC . Changes in total leg volume during lower body negative pressure. Aerosp Med 40: 602‐606, 1969.
 161. Nelson E , Rennels M . Innervation of intracranial arteries. Brain 93: 475‐490, 1970.
 162. Neutze JM , Wyler F , Rudolph AM . Changes in distribution of cardiac output after hemorrhage in rabbits. Am J Physiol 215: 857‐864, 1968.
 163. Newell DW , Aaslid R , Lam A , Mayberg TS , Winn HR . Comparison of flow and velocity during dynamic autoregulation testing in humans. Stroke 25: 793‐797, 1994.
 164. Nolte J , Sundsten J . Human Brain: An Introduction to its Functional Anatomy. Philadelphia, PA: Mosby Elsevier, 2009.
 165. Numan T , Bain AR , Hoiland RL , Smirl JD , Lewis NC , Ainslie PN . Static autoregulation in humans: A review and reanalysis. Med Eng Phys 36: 1487‐1495, 2014.
 166. Oberg B , Thoren P . Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat. A possible cause of the vaso‐vagal reaction. Acta Physiol Scand 85: 164‐173, 1972.
 167. Ogoh S , Brothers RM , Barnes Q , Eubank WL , Hawkins MN , Purkayastha S , O‐Yurvati A , Raven PB . The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise. J Physiol 569: 697‐704, 2005.
 168. Ogoh S , Brothers RM , Eubank WL , Raven PB . Autonomic neural control of the cerebral vasculature: Acute hypotension. Stroke 39: 1979‐1987, 2008.
 169. Ogoh S , Nakahara H , Okazaki K , Bailey DM , Miyamoto T . Cerebral hypoperfusion modifies the respiratory chemoreflex during orthostatic stress. Clin Sci (Lond) 125: 37‐44, 2013.
 170. Ogoh S , Nakahara H , Ueda S , Okazaki K , Shibasaki M , Subudhi AW , Miyamoto T . Effects of acute hypoxia on cerebrovascular responses to carbon dioxide. Exp Physiol 99: 849‐858, 2014.
 171. Ogoh S , Sato K , Fisher JP , Seifert T , Overgaard M , Secher NH . The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects. Clin Physiol Funct Imaging 31: 445‐451, 2011.
 172. Ogoh S , Sato K , Nakahara H , Okazaki K , Subudhi AW , Miyamoto T . Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries. Exp Physiol 98: 692‐698, 2013.
 173. Onoe M , Mori A , Watarida S , Sugita T , Shiraishi S , Nojima T , Nakajima Y , Tabata R , Matsuno S . The effect of pulsatile perfusion on cerebral blood flow during profound hypothermia with total circulatory arrest. J Thorac Cardiovasc Surg 108: 119‐125, 1994.
 174. Panerai RB . Assessment of cerebral pressure autoregulation in humans–a review of measurement methods. Physiol Meas 19: 305‐338, 1998.
 175. Pasztor E , Symon L , Dorsch NW , Branston NM . The hydrogen clearance method in assessment of blood flow in cortex, white matter and deep nuclei of baboons. Stroke 4: 556‐567, 1973.
 176. Paulson OB , Strandgaard S , Edvinsson L . Cerebral autoregulation. Cerebrovasc Brain Metab Rev 2: 161‐192, 1990.
 177. Pawelczyk JA , Matzen S , Friedman DB , Secher NH . Cardiovascular and hormonal responses to central hypovolemia in humans. In: Secher NH , Pawelczyk JA , Ludbrook J , editors. Blood Loss and Shock. London, UK: Edward Arnold, 1994, pp. 25‐36.
 178. Pearce WJ , D'Alecy LG . Hemorrhage‐induced cerebral vasoconstriction in dogs. Stroke 11: 190‐197, 1980.
 179. Peebles KC , Ball OG , MacRae BA , Horsman HM , Tzeng YC . Sympathetic regulation of the human cerebrovascular response to carbon dioxide. J Appl Physiol 113: 700‐706, 2012.
 180. Peterson CG , Haugen FP . Hemorrhagic Shock and the Nervous System. Am J Surg 106: 233‐242, 1963.
 181. Phillips AA , Ainslie PN , Krassioukov AV , Warburton DE . Regulation of cerebral blood flow after spinal cord injury. J Neurotrauma 30: 1551‐1563, 2013.
 182. Phillips AA , Warburton DE , Ainslie PN , Krassioukov AV . Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high‐level spinal cord injury: Improved by alpha‐1 agonist midodrine hydrochloride. J Cereb Blood Flow Metab 34: 794‐801, 2014.
 183. Plaisance P , Lurie KG , Vicaut E , Martin D , Gueugniaud P‐Y , Petit JL , Payen D . Evaluation of an impedance threshold device in patients receiving active compression‐decompression cardiopulmonary resuscitation for out of hospital cardiac arrest. Resuscitation 61: 265‐271, 2004.
 184. Pollard V , Prough DS , DeMelo AE , Deyo DJ , Uchida T , Stoddart HF . Validation in volunteers of a near‐infrared spectroscope for monitoring brain oxygenation in vivo. Anesth Analg 82: 269‐277, 1996.
 185. Powers WJ . Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol 29: 231‐240, 1991.
 186. Przybylowski T , Bangash MF , Reichmuth K , Morgan BJ , Skatrud JB , Dempsey JA . Mechanisms of the cerebrovascular response to apnoea in humans. J Physiol 548: 323‐332, 2003.
 187. Purkayastha S , Sorond F . Transcranial Doppler ultrasound: Technique and application. Semin Neurol 32: 411‐420, 2012.
 188. Purves MJ . Do vasomotor nerves significantly regulate cerebral blood flow? Circ Res 43: 485‐493, 1978.
 189. Rea RF , Hamdan M , Clary MP , Randels MJ , Dayton PJ , Strauss RG . Comparison of muscle sympathetic responses to hemorrhage and lower body negative pressure in humans. J Appl Physiol 70: 1401‐1405, 1991.
 190. Reich T , Rusinek H . Cerebral cortical and white matter reactivity to carbon dioxide. Stroke 20: 453‐457, 1989.
 191. Rickards CA , Johnson BD , Harvey RE , Convertino VA , Joyner MJ , Barnes JN . Cerebral blood velocity regulation during progressive blood loss compared to lower body negative pressure in humans. J Appl Physiol (in press), 2015.
 192. Rickards CA , Ryan KL , Cooke WH , Convertino VA . Tolerance to central hypovolemia: The influence of oscillations in arterial pressure and cerebral blood velocity. J Appl Physiol 111: 1048‐1058, 2011.
 193. Rickards CA , Ryan KL , Cooke WH , Lurie KG , Convertino VA . Inspiratory resistance delays the reporting of symptoms with central hypovolemia: Association with cerebral blood flow. Am J Physiol 293: R243‐250, 2007.
 194. Rickards CA , Tzeng YC . Arterial pressure and cerebral blood flow variability: Friend or foe? A review. Front Physiol 5: 120, 2014.
 195. Rowell LB. Human Cardiovascular Control. New York, NY: Oxford University Press, 1993.
 196. Ryou MG , Liu R , Ren M , Sun J , Mallet RT , Yang SH . Pyruvate protects the brain against ischemia‐reperfusion injury by activating the erythropoietin signaling pathway. Stroke 43: 1101‐1107, 2012.
 197. Sahota IS , Ravensbergen HR , McGrath MS , Claydon VE . Cerebrovascular responses to orthostatic stress after spinal cord injury. J Neurotrauma 29: 2446‐2456, 2012.
 198. Sanderson JM , Wright G , Sims FW . Brain damage in dogs immediately following pulsatile and non‐pulsatile blood flows in extracorporeal circulation. Thorax 27: 275‐286, 1972.
 199. Sandor P . Nervous control of the cerebrovascular system: Doubts and facts. Neurochem Int 35: 237‐259, 1999.
 200. Santry HP , Alam HB . Fluid resuscitation: Past, present, and the future. Shock 33: 229‐241, 2010.
 201. Sapirstein LA , Sapirstein EH , Bredemeyer A . Effect of hemorrhage on the cardiac output and its distribution in the rat. Circ Res 8: 135‐148, 1960.
 202. Sato K , Fisher JP , Seifert T , Overgaard M , Secher NH , Ogoh S . Blood flow in internal carotid and vertebral arteries during orthostatic stress. Exp Physiol 97: 1272‐1280, 2012.
 203. Sato K , Sadamoto T , Hirasawa A , Oue A , Subudhi AW , Miyazawa T , Ogoh S . Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries. J Physiol 590: 3277‐3290, 2012.
 204. Schadt JC , Ludbrook J . Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol 260: H305‐318, 1991.
 205. Schlader ZJ , Seifert T , Wilson TE , Bundgaard‐Nielsen M , Secher NH , Crandall CG . Acute volume expansion attenuates hyperthermia‐induced reductions in cerebral perfusion during simulated hemorrhage. J Appl Physiol 114: 1730‐1735, 2013.
 206. Schmidt BM , Rezende‐Neto JB , Andrade MV , Winter PC , Carvalho MG, Jr , Lisboa TA , Rizoli SB , Cunha‐Melo JR . Permissive hypotension does not reduce regional organ perfusion compared to normotensive resuscitation: Animal study with fluorescent microspheres. World J Emerg Surg 7(Suppl 1): S9, 2012.
 207. Schmidt JF , Paulson OB . Cerebral blood flow and hypovolaemic shock. In: Secher NH , Pawelczyk JA , Ludbrook J , editors. Blood Loss and Shock. London, UK: Edward Arnold, 1994, pp. 95‐107.
 208. Secher NH , Van Lieshout JJ . Heart rate during haemorrhage: Time for reappraisal. J Physiol 588: 19, 2010.
 209. Secher NH , Van Lieshout JJ . Normovolaemia defined by central blood volume and venous oxygen saturation. Clin Exp Pharmacol Physiol 32: 901‐910, 2005.
 210. Serrador JM , Picot PA , Rutt BK , Shoemaker JK , Bondar RL . MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke 31: 1672‐1678, 2000.
 211. Serrador JM , Sorond FA , Vyas M , Gagnon M , Iloputaife ID , Lipsitz LA . Cerebral pressure‐flow relations in hypertensive elderly humans: Transfer gain in different frequency domains. J Appl Physiol 98: 151‐159, 2005.
 212. Shackford SR , Schmoker JD , Zhuang J . The effect of hypertonic resuscitation on pial arteriolar tone after brain injury and shock. J Trauma 37: 899‐908, 1994.
 213. Shaz BH , Winkler AM , James AB , Hillyer CD , MacLeod JB . Pathophysiology of early trauma‐induced coagulopathy: Emerging evidence for hemodilution and coagulation factor depletion. J Trauma 70: 1401‐1407, 2011.
 214. Shenkin HA , Cheney RH , Govons SR , Hardy JD , Fletcher AG . On the diagnosis of hemorrhage in man ‐ a study of volunteers bled large amounts. Am J Med Sci 208: 421‐436, 1944.
 215. Shepard RB , Simpson DC , Sharp JF . Energy equivalent pressure. Arch Surg 93: 730‐740, 1966.
 216. Shimoda LA , Norins NA , Madden JA . Responses to pulsatile flow in piglet isolated cerebral arteries. Pediatr Res 43: 514‐520, 1998.
 217. Shoemaker JK , Usselman CW , Rothwell A , Wong SW . Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning. Exp Physiol 97: 1249‐1262, 2012.
 218. Skow RJ , MacKay CM , Tymko MM , Willie CK , Smith KJ , Ainslie PN , Day TA . Differential cerebrovascular CO2 reactivity in anterior and posterior cerebral circulations. Respir Physiol Neurobiol 189: 76‐86, 2013.
 219. Sondeen JL , Coppes VG , Holcomb JB . Blood pressure at which rebleeding occurs after resuscitation in swine with aortic injury. J Trauma 54: S110‐117, 2003.
 220. Sorensen H , Grocott HP , Niemann M , Rasmussen A , Hillingso JG , Frederiksen HJ , Secher NH . Ventilatory strategy during liver transplantation: Implications for near‐infrared spectroscopy‐determined frontal lobe oxygenation. Front Physiol 5: 321, 2014.
 221. Sorensen H , Rasmussen P , Siebenmann C , Zaar M , Hvidtfeldt M , Ogoh S , Sato K , Kohl‐Bareis M , Secher NH , Lundby C . Extra‐cerebral oxygenation influence on near‐infrared‐spectroscopy‐determined frontal lobe oxygenation in healthy volunteers: A comparison between INVOS‐4100 and NIRO‐200NX. Clin Physiol Funct Imaging, 2014 [Epub ahead of print].
 222. Sorensen H , Secher NH , Siebenmann C , Nielsen HB , Kohl‐Bareis M , Lundby C , Rasmussen P . Cutaneous vasoconstriction affects near‐infrared spectroscopy determined cerebral oxygen saturation during administration of norepinephrine. Anesthesiology 117: 263‐270, 2012.
 223. Stamatovic SM , Dimitrijevic OB , Keep RF , Andjelkovic AV . Inflammation and brain edema: New insights into the role of chemokines and their receptors. Acta Neurochir Suppl 96: 444‐450, 2006.
 224. Stauss HM . Identification of blood pressure control mechanisms by power spectral analysis. Clin Exp Pharmacol Physiol 34: 362‐368, 2007.
 225. Stevens PM , Lamb LE . Effects of lower body negative pressure on the cardiovascular system. Am J Cardiol 16: 506‐515, 1965.
 226. Stewart JM , Medow MS , DelPozzi A , Messer ZR , Terilli C , Schwartz CE . Middle cerebral O2 delivery during the modified Oxford maneuver increases with sodium nitroprusside and decreases during phenylephrine. Am J Physiol Heart Circ Physiol 304: H1576‐1583, 2013.
 227. Stewart JM , Rivera E , Clarke DA , Baugham IL , Ocon AJ , Taneja I , Terilli C , Medow MS . Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation. Am J Physiol Heart Circ Physiol 300: H1492‐1500, 2011.
 228. Strandgaard S , Jones JV , MacKenzie ET , Harper AM . Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res 37: 164‐167, 1975.
 229. Strandgaard S , Olesen J , Skinhoj E , Lassen NA . Autoregulation of brain circulation in severe arterial hypertension. Br Med J 1: 507‐510, 1973.
 230. Strandgaard S , Sigurdsson ST . Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Counterpoint: Sympathetic nerve activity does not influence cerebral blood flow. J Appl Physiol 105: 1366‐1367; discussion 1367‐1368, 2008.
 231. Summers RL , Ward KR , Witten T , Convertino VA , Ryan KL , Coleman TG , Hester RL . Validation of a computational platform for the analysis of the physiologic mechanisms of a human experimental model of hemorrhage. Resuscitation 80: 1405‐1410, 2009.
 232. Szabo K , Rosengarten B , Juhasz T , Lako E , Csiba L , Olah L . Effect of non‐steroid anti‐inflammatory drugs on neurovascular coupling in humans. J Neurol Sci 336: 227‐231, 2014.
 233. Tan CO . Defining the characteristic relationship between arterial pressure and cerebral flow. J Appl Physiol 113: 1194‐1200, 2012.
 234. Tan CO , Hamner JW , Taylor JA . The role of myogenic mechanisms in human cerebrovascular regulation. J Physiol 591: 5095‐5105, 2013.
 235. Thomas KN , Cotter JD , Galvin SD , Williams MJ , Willie CK , Ainslie PN . Initial orthostatic hypotension is unrelated to orthostatic tolerance in healthy young subjects. J Appl Physiol 107: 506‐517, 2009.
 236. Torella F , Cowley RD , Thorniley MS , McCollum CN . Regional tissue oxygenation during hemorrhage: Can near infrared spectroscopy be used to monitor blood loss? Shock 18: 440‐444, 2002.
 237. Torres Filho IP , Torres LN , Pittman RN . Early physiologic responses to hemorrhagic hypotension. Transl Res 155: 78‐88, 2010.
 238. Torres LN , Torres Filho IP , Barbee RW , Tiba MH , Ward KR , Pittman RN . Systemic responses to prolonged hemorrhagic hypotension. Am J Physiol Heart Circ Physiol 286: H1811‐1820, 2004.
 239. American College of Surgeons Committee on Trauma. Shock. In: McSwain NE , Salomone JP , Pons PT , editors. Prehospital Trauma Life Support. St. Louis, MO: Mosby JEMS, 2011, pp. 179‐212.
 240. Tsukamoto T , Pape HC . Animal models for trauma research: What are the options? Shock 31: 3‐10, 2009.
 241. Tzeng YC , Ainslie PN . Blood pressure regulation IX: Cerebral autoregulation under blood pressure challenges. Eur J Appl Physiol 114: 545‐559, 2014.
 242. Tzeng YC , Ainslie PN , Cooke WH , Peebles KC , Willie CK , MacRae BA , Smirl JD , Horsman HM , Rickards CA . Assessment of cerebral autoregulation: The quandary of quantification. Am J Physiol 303: H658‐671, 2012.
 243. Tzeng YC , Chan GS , Willie CK , Ainslie PN . Determinants of human cerebral pressure‐flow velocity relationships: New insights from vascular modelling and Ca2+ channel blockade. J Physiol 589: 3263‐3274, 2011.
 244. Tzeng YC , Willie CK , Atkinson G , Lucas SJ , Wong A , Ainslie PN . Cerebrovascular regulation during transient hypotension and hypertension in humans. Hypertension 56: 268‐273, 2010.
 245. Uryash A , Wu H , Bassuk J , Kurlansky P , Sackner MA , Adams JA . Low‐amplitude pulses to the circulation through periodic acceleration induces endothelial‐dependent vasodilatation. J Appl Physiol 106: 1840‐1847, 2009.
 246. Vaddadi G , Esler MD , Dawood T , Lambert E . Persistence of muscle sympathetic nerve activity during vasovagal syncope. Eur Heart J 31: 2027‐2033, 2010.
 247. Valdueza JM , Balzer JO , Villringer A , Vogl TJ , Kutter R , Einhaupl KM . Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: Assessment with MR and transcranial Doppler sonography. Am J Neuroradiol 18: 1929‐1934, 1997.
 248. Valdueza JM , von Munster T , Hoffman O , Schreiber S , Einhaupl KM . Postural dependency of the cerebral venous outflow. Lancet 355: 200‐201, 2000.
 249. van Lieshout JJ , Pott F , Madsen PL , van Goudoever J , Secher NH . Muscle tensing during standing: Effects on cerebral tissue oxygenation and cerebral artery blood velocity. Stroke 32: 1546‐1551, 2001.
 250. van Lieshout JJ , Secher NH . Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Point: Sympathetic activity does influence cerebral blood flow. J Appl Physiol 105: 1364‐1366, 2008.
 251. van Lieshout JJ , Wieling W , Karemaker JM , Secher NH . Syncope, cerebral perfusion, and oxygenation. J Appl Physiol 94: 833‐848, 2003.
 252. Van Mil AHM , Spilt A , Van Buchem MA , Bollen ELEM , Teppema L , Westendorp RGJ , Blauw GJ . Nitric oxide mediates hypoxia‐induced cerebral vasodilation in humans. J Appl Physiol 92: 962‐966, 2002.
 253. Verbree J , Bronzwaer AS , Ghariq E , Versluis MJ , Daemen MJ , van Buchem MA , Dahan A , Van Lieshout JJ , van Osch MJ . Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra high‐field MRI. J Appl Physiol 117: 1084‐1089, 2014.
 254. Vladeck BC , Bassin R , Kark AE , Shoemaker WC . Rapid and slow hemorrhage in man. II. Sequential acid‐base and oxygen transport responses. Ann Surg 173: 331‐336, 1971.
 255. Wallace JP , Sharpey‐Schafer EP . Blood changes following controlled hemorrhage in man. Lancet 2: 393‐395, 1941.
 256. Ward KR , Tiba MH , Ryan KL , Filho IP , Rickards CA , Witten T , Soller BR , Ludwig DA , Convertino VA . Oxygen transport characterization of a human model of progressive hemorrhage. Resuscitation 81: 987‐993, 2010.
 257. Waschke KF , Albrecht DM , van Ackern K , Kuschinsky W . Autoradiographic determination of regional cerebral blood flow and metabolism in conscious rats after fluid resuscitation from haemorrhage with a haemoglobin‐based oxygen carrier. Br J Anaesth 73: 522‐528, 1994.
 258. Waschke KF , Albrecht DM , van Ackern K , Kuschinsky W . Coupling between local cerebral blood flow and metabolism after hypertonic/hyperoncotic fluid resuscitation from hemorrhage in conscious rats. Anesth Analg 82: 52‐60, 1996.
 259. Waschke KF , Riedel M , Albrecht DM , van Ackern K , Kuschinsky W . Effects of a perfluorocarbon emulsion on regional cerebral blood flow and metabolism after fluid resuscitation from hemorrhage in conscious rats. Anesth Analg 79: 874‐882, 1994.
 260. West JB . Respiratory Physiology: The Essentials. Baltimore, MD: Lippincott Williams & Wilkins, 2012.
 261. Williamson EB , Bronas UG , Dengel DR . Automated edge detection versus manual edge measurement in analysis of brachial artery reactivity: A comparison study. Ultrasound Med Biol 34: 1499‐1503, 2008.
 262. Willie CK , Colino FL , Bailey DM , Tzeng YC , Binsted G , Jones LW , Haykowsky MJ , Bellapart J , Ogoh S , Smith KJ , Smirl JD , Day TA , Lucas SJ , Eller LK , Ainslie PN . Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function. J Neurosci Methods 196: 221‐237, 2011.
 263. Willie CK , Cowan EC , Ainslie PN , Taylor CE , Smith KJ , Sin PY , Tzeng YC . Neurovascular coupling and distribution of cerebral blood flow during exercise. J Neurosci Methods 198: 270‐273, 2011.
 264. Willie CK , Macleod DB , Shaw AD , Smith KJ , Tzeng YC , Eves ND , Ikeda K , Graham J , Lewis NC , Day TA , Ainslie PN . Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol 590: 3261‐3275, 2012.
 265. Willie CK , Smith KJ , Day TA , Ray LA , Lewis NC , Bakker A , Macleod DB , Ainslie PN . Regional cerebral blood flow in humans at high altitude: Gradual ascent and 2 wk at 5,050 m. J Appl Physiol 116: 905‐910, 2014.
 266. Willie CK , Tzeng YC , Fisher JA , Ainslie PN . Integrative regulation of human brain blood flow. J Physiol 592: 841‐859, 2014.
 267. Wilson MH , Edsell ME , Davagnanam I , Hirani SP , Martin DS , Levett DZ , Thornton JS , Golay X , Strycharczuk L , Newman SP , Montgomery HE , Grocott MP , Imray CH . Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia–an ultrasound and MRI study. J Cereb Blood Flow Metab 31: 2019‐2029, 2011.
 268. Wintermark M , Sesay M , Barbier E , Borbely K , Dillon WP , Eastwood JD , Glenn TC , Grandin CB , Pedraza S , Soustiel JF , Nariai T , Zaharchuk G , Caille JM , Dousset V , Yonas H . Comparative overview of brain perfusion imaging techniques. Stroke 36: e83‐e99, 2005.
 269. Wolthuis RA , Bergman SA , Nicogossian AE . Physiological effects of locally applied reduced pressure in man. Physiol Rev 54: 566‐595, 1974.
 270. Wolthuis RA , LeBlanc A , Carpentier WA , Bergman SA, Jr . Response of local vascular volumes to lower body negative pressure stress. Aviat Space Environ Med 46: 697‐702, 1975.
 271. Woodman RJ , Playford DA , Watts GF , Cheetham C , Reed C , Taylor RR , Puddey IB , Beilin LJ , Burke V , Mori TA , Green D . Improved analysis of brachial artery ultrasound using a novel edge‐detection software system. J Appl Physiol 91: 929‐937, 2001.
 272. Yannopoulos D , McKnite S , Metzger A , Lurie KG . Intrathoracic pressure regulation improves 24‐hour survival in a porcine model of hypovolemic shock. Anesth Analg 104: 157‐162, 2007.
 273. Yannopoulos D , McKnite SH , Lurie KG . Intrathoracic pressure regulation for intracranial pressure management in normovolemic and hypovolemic pigs. Crit Care Med 34: S495‐500, 2006.
 274. Yannopoulos D , Metzger A , McKnite S , Nadkarni V , Aufherheide TP , Idris A , Dries D , Benditt DG , Lurie KG . Intrathoracic pressure regulation improves vital organ perfusion pressures in normovolemic and hypovolemic pigs. Resuscitation 70: 445‐453, 2006.
 275. Yu W , Hu S , Xie ZY , He ZJ , Luo HM , Lin HY , Zhou FQ , Sheng ZY . Pyruvate oral rehydration solution improved visceral function and survival in shock rats. J Surg Res 2014.
 276. Zamboni P , Menegatti E , Pomidori L , Morovic S , Taibi A , Malagoni AM , Cogo AL , Gambaccini M . Does thoracic pump influence the cerebral venous return? J Appl Physiol 112: 904‐910, 2012.
 277. Zhang P , Huang G , Shi X . Cerebral vasoreactivity during hypercapnia is reset by augmented sympathetic influence. J Appl Physiol 110: 352‐358, 2011.
 278. Zhang R , Levine BD . Autonomic ganglionic blockade does not prevent reduction in cerebral blood flow velocity during orthostasis in humans. Stroke 38: 1238‐1244, 2007.
 279. Zhang R , Zuckerman J , Iwasaki K , Wilson TE , Crandall CG , Levine BD . Autonomic neural control of dynamic cerebral autoregulation in humans. Circulation 106: 1814‐1820, 2002.
 280. Zhang R , Zuckerman JH , Giller CA , Levine BD . Transfer function analysis of dynamic cerebral autoregulation in humans. Am J Physiol 274: H233‐241, 1998.
 281. Zhang R , Zuckerman JH , Levine BD . Deterioration of cerebral autoregulation during orthostatic stress: Insights from the frequency domain. J Appl Physiol 85: 1113‐1122, 1998.

Related Articles:

Cerebral Circulation
The Cerebral Microcirculation
Neurogenic Control of the Vascular System: Focus on Cerebral Circulation
Brain Blood Flow and Control of Breathing

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Cerebral Blood‐Flow Regulation During Hemorrhage
 

How to Cite

Caroline A. Rickards. Cerebral Blood‐Flow Regulation During Hemorrhage. Compr Physiol 2015, 5: 1585-1621. doi: 10.1002/cphy.c140058