Cerebrovascular Dynamics and Vascular Endothelial Growth Factor in Acute Mountain Sickness

Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Wilderness and Environmental Medicine (Impact Factor: 1.2). 02/2006; 17(1):1-7. DOI: 10.1580/1080-6032(2006)17[1:CDAVEG]2.0.CO;2
Source: PubMed


To determine if serum vascular endothelial growth factor (VEGF) and ultrasonic monitoring of vascular dynamics with dynamic vascular analysis at sea level and high altitude correlate with acute mountain sickness symptoms.
Nine volunteers participated in a staged ascent from sea level to 4300 m undergoing complete transcranial Doppler studies with dynamic vascular analysis. Serum VEGF levels, Lake Louise scores, Spielberger-1 scores, Subjective Exercise Experiences Scale positive scores, and Symptom Checklist-90 surveys were collected after 24 hours at each altitude.
Symptom scores, index of pulsatility, and dynamic flow index differentiated the subjects into 2 distinct groups. Symptomatic subjects had increased VEGF levels at sea level but decreased levels at 4300 m. The dynamic flow index increased in symptomatic subjects at 4300 m compared with the asymptomatic subjects. The mean flow velocity increased in both groups and could not be used to differentiate the subjects.
Altered vascular physiology is associated with acute mountain sickness. Increased vascular permeability increases vascular capacitance, with an increase in dynamic flow index to meet these demands. Altered vascular dynamics were associated with high-altitude cerebral edema in 1 subject. Dynamic vascular analysis demonstrated altered vascular pathophysiology associated with acute mountain sickness. Changes in VEGF were meaningful when interpreted with the dynamic vascular analysis findings. These physiological findings may help explain the vascular changes associated with hypocarbic hypoxemia at altitude.

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    • "cerebral blood flow is believed to be one of the compensatory mechanisms serving to maintain normal oxygen flux to the brain in the face of arterial hypoxemia (Wilson et al., 2009). For the last 40 years, transcranial Doppler (TCD) measurement of flow velocity in the middle cerebral artery (MCA) has been widely used as a surrogate marker for cerebral blood flow (CBF), both at rest and during exercise at altitude (Aaslid et al., 1982; Otis et al., 1989; Baumgartner et al., 1994, 1999; Jansen et al., 2000, 2002; Ter Minassian et al., 2001; Appenzeller et al., 2004; Lysakowski et al., 2004; Norcliffe et al., 2005; van Osta et al., 2005; Imray et al., 2005; Palma et al., 2006; Ainslie et al., 2007; Subudhi et al., 2008). "
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    ABSTRACT: Abstract Imray, Christopher, Colin Chan, Alison Stubbings, Hannah Rhodes, Susannah Patey, Mark H. Wilson, Damian M. Bailey, and Alex D. Wright for the Birmingham Medical Research Expeditionary Society. Time course variations in the mechanisms by which cerebral oxygen delivery is maintained on exposure to hypoxia/altitude. High Alt Med Biol 15:000-000, 2014.-Normal cerebral function is dependent upon an adequate and continuous supply of oxygen. This study calculated cerebral blood flow based on assessment of the right middle cerebral artery (MCA) velocity (MCAVel) and MCA diameter (MCADiam) by trans-cranial Doppler and trans-cranial Duplex in normoxia, during acute exposure to 12% normobaric hypoxia for up to 6 hours, and after 3 days exposure to the equivalent altitude, 4392 m, in nine subjects. Mean (SD) MCAVel increased both after 6 hours hypoxia from 76.8 (11.4) to 97.2 (17.4) cms/sec (p<0.001), and after 3 days at altitude from 68.1 (7.5) [sea level] to 76.2 (10.2) [4392 m] (p=0.015). MCADiam increased from 5.07 (0.6) to 6.1 (0.6) mm (p<0.001) after 6 hours of 12% hypoxia. Calculated mean MCA blood flow increased after 6 hours of 12% hypoxia from 5.0 (0.6) mL/sec to 8.9 (1.2) mL/sec, but there was no difference between sea level and 4392 m. Calculated mean cerebral oxygen delivery increased from 72.4 (14.4) to 107 (20.1) mL/sec (p<0.001) after 6 hours of 12% hypoxia and was maintained unchanged at 4392 m. An increase in MCA caliber, rather than blood velocity, was a major contributor to increased oxygen delivery accompanying within the first few hours of exposure to acute hypoxia. During more long-term exposure, increases in MCA velocity and a rise in hemoglobin appeared to be the more important mechanisms in maintaining cerebral oxygen delivery. The implication of this observed change in MCA diameter questions the widely held assumption that MCA velocity is a surrogate for flow during acute hypoxic exposure.
    High altitude medicine & biology 02/2014; 15(1). DOI:10.1089/ham.2013.1079 · 1.28 Impact Factor
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    • "A greater understanding of the cerebrovascular response to hypoxia is thus of broad interest, as would be the validation of clinically relevant techniques to assess flow in intracranial vessels. Transcranial Doppler (TCD) measurement of flow velocity in the middle cerebral artery (MCA) has been used to assess CBF dynamics both at rest and during exercise at altitude (Ainslie et al, 2007; Appenzeller et al, 2004; Baumgartner et al, 1994, 1999; Feddersen et al, 2007; Imray et al, 2005; Jansen et al, 2000, 2002; Lysakowski et al, 2004; Norcliffe et al, 2005; Otis et al, 1989; Palma et al, 2006; Subudhi et al, 2007; Ter Minassian et al, 2001; Van Osta et al, 2005). Assuming cerebral arterial diameter remains constant in the face of sustained hypoxia, investigators have inferred changes in CBF from changes in the velocity of blood in the MCA. "
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    ABSTRACT: Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n=24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO(2)=12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n=7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 06/2011; 31(10):2019-29. DOI:10.1038/jcbfm.2011.81 · 5.41 Impact Factor
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