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Article ; Online: Manipulation of iron status on cerebral blood flow at high altitude in lowlanders and adapted highlanders.

Patrician, Alexander / Willie, Christopher / Hoiland, Ryan L / Gasho, Christopher / Subedi, Prajan / Anholm, James D / Tymko, Michael M / Ainslie, Philip N

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2023 Volume 43, Issue 7, Page(s) 1166–1179

Abstract: Cerebral blood flow (CBF) increases during hypoxia to counteract the reduction in arterial oxygen content. The onset of tissue hypoxemia coincides with the stabilization of hypoxia-inducible factor (HIF) and transcription of downstream HIF-mediated ... ...

Abstract	Cerebral blood flow (CBF) increases during hypoxia to counteract the reduction in arterial oxygen content. The onset of tissue hypoxemia coincides with the stabilization of hypoxia-inducible factor (HIF) and transcription of downstream HIF-mediated processes. It has yet to be determined, whether HIF down- or upregulation can modulate hypoxic vasodilation of the cerebral vasculature. Therefore, we examined whether: 1) CBF would increase with iron depletion (via chelation) and decrease with repletion (via iron infusion) at high-altitude, and 2) explore whether genotypic advantages of highlanders extend to HIF-mediated regulation of CBF. In a double-blinded and block-randomized design, CBF was assessed in 82 healthy participants (38 lowlanders, 20 Sherpas and 24 Andeans), before and after the infusion of either: iron(III)-hydroxide sucrose, desferrioxamine or saline. Across both lowlanders and highlanders, baseline iron levels contributed to the variability in cerebral hypoxic reactivity at high altitude (R
MeSH term(s)	Humans ; Altitude ; Acclimatization/physiology ; Deferoxamine ; Ferric Compounds ; Hypoxia ; Cerebrovascular Circulation ; Altitude Sickness
Chemical Substances	Deferoxamine (J06Y7MXW4D) ; Ferric Compounds
Language	English
Publishing date	2023-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1177/0271678X231152734
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Article ; Online: Pulmonary vascular reactivity to supplemental oxygen in Sherpa and lowlanders during gradual ascent to high altitude.

Subedi, Prajan / Gasho, Christopher / Stembridge, Michael / Williams, Alexandra M / Patrician, Alexander / Ainslie, Philip N / Anholm, James D

Experimental physiology

2022 Volume 108, Issue 1, Page(s) 111–122

Abstract: New findings: What is the central question of this study? How does hypoxic pulmonary vasoconstriction and the response to supplemental oxygen change over time at high altitude? What is the main finding and its importance? Lowlanders and partially de- ... ...

Abstract	New findings: What is the central question of this study? How does hypoxic pulmonary vasoconstriction and the response to supplemental oxygen change over time at high altitude? What is the main finding and its importance? Lowlanders and partially de-acclimatized Sherpa both demonstrated pulmonary vascular responsiveness to supplemental oxygen that was maintained for 12 days' exposure to progressively increasing altitude. An additional 2 weeks' acclimatization at 5050 m altitude rendered the pulmonary vasculature minimally responsive to oxygen similar to the fully acclimatized non-ascent Sherpa. Additional hypoxic exposure at that time point did not augment hypoxic pulmonary vasoconstriction. Abstract: Prolonged alveolar hypoxia leads to pulmonary vascular remodelling. We examined the time course at altitude, over which hypoxic pulmonary vasoconstriction goes from being acutely reversible to potentially irreversible. Study subjects were lowlanders (n = 20) and two Sherpa groups. All Sherpa were born and raised at altitude. One group (ascent Sherpa, n = 11) left altitude and after de-acclimatization in Kathmandu for ∼7 days re-ascended with the lowlanders over 8-10 days to 5050 m. The second Sherpa group (non-ascent Sherpa, n = 12) remained continuously at altitude. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured while breathing ambient air and following supplemental oxygen. During ascent PASP and PVR increased in lowlanders and ascent Sherpa; however, with supplemental oxygen, lowlanders had significantly greater decrease in PASP (P = 0.02) and PVR (P = 0.02). After ∼14 days at 5050 m, PASP decreased with supplemental oxygen (mean decrease: 3.9 mmHg, 95% CI 2.1-5.7 mmHg, P < 0.001); however, PVR was unchanged (P = 0.49). In conclusion, PASP and PVR increased with gradual ascent to altitude and decreased via oxygen supplementation in both lowlanders and ascent Sherpa. Following ∼14 days at 5050 m altitude, there was no change in PVR to hypoxia or O
MeSH term(s)	Humans ; Altitude ; Hypoxia ; Altitude Sickness ; Acclimatization/physiology ; Oxygen
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2022-11-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1016295-1
ISSN	1469-445X ; 0958-0670
ISSN (online)	1469-445X
ISSN	0958-0670
DOI	10.1113/EP090458
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Article ; Online: Hemorheological, cardiorespiratory, and cerebrovascular effects of pentoxifylline following acclimatization to 3,800 m.

Steele, Andrew R / Howe, Connor A / Gibbons, Travis D / Foster, Katharine / Williams, Alexandra M / Caldwell, Hannah G / Brewster, L Madden / Duffy, Jennifer / Monteleone, Justin A / Subedi, Prajan / Anholm, James D / Stembridge, Mike / Ainslie, Philip N / Tremblay, Joshua C

American journal of physiology. Heart and circulatory physiology

2024 Volume 326, Issue 3, Page(s) H705–H714

Abstract: Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and ... ...

Abstract	Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, ∼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg;
MeSH term(s)	Male ; Humans ; Female ; Young Adult ; Adult ; Pentoxifylline/pharmacology ; Pentoxifylline/therapeutic use ; Hemorheology ; Tumor Necrosis Factor-alpha ; Hypoxia ; Oxygen ; Acclimatization/physiology ; Inflammation/complications ; Gases ; Cerebrovascular Circulation ; Altitude
Chemical Substances	Pentoxifylline (SD6QCT3TSU) ; Tumor Necrosis Factor-alpha ; Oxygen (S88TT14065) ; Gases
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00783.2023
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Article ; Online: Left Ventricular Twist Is Augmented in Hypoxia by β

Williams, Alexandra M / Ainslie, Philip N / Anholm, James D / Gasho, Chris / Subedi, Prajan / Stembridge, Mike

Circulation. Cardiovascular imaging

2019 Volume 12, Issue 5, Page(s) e008455

Abstract: Background: Left ventricular (LV) twist mechanics are augmented with both acute and chronic hypoxemia. Although the underlying mechanisms remain unknown, sympathetic activation and a direct effect of hypoxemia on the myocardium have been proposed, the ... ...

Abstract	Background: Left ventricular (LV) twist mechanics are augmented with both acute and chronic hypoxemia. Although the underlying mechanisms remain unknown, sympathetic activation and a direct effect of hypoxemia on the myocardium have been proposed, the latter of which may produce subendocardial dysfunction that is masked by larger subepicardial torque. This study therefore sought to (1) determine the individual and combined influences of β Methods: Twelve males (27±4 years) were tested near sea level in acute hypoxia (Spo Results: At sea level, compared with baseline (14.8±3.0°) LV twist was reduced with esmolol (11.2±3.3°; P=0.007) and augmented during hypoxia (19.6±4.9°; P<0.001), whereas esmolol+hypoxia augmented twist compared with esmolol alone (16.5±3.3°; P<0.001). At 5050 m, LV twist was increased compared with sea level (19.5±5.4°; P=0.004), and reduced with esmolol (13.0±3.8°; P<0.001) and Spo Conclusions: These findings suggest LV twist is augmented in hypoxia via β
MeSH term(s)	Acclimatization ; Adrenergic beta-1 Receptor Antagonists/administration & dosage ; Adult ; Altitude ; Biomechanical Phenomena ; British Columbia ; Cross-Over Studies ; Double-Blind Method ; Humans ; Hypoxia/blood ; Hypoxia/complications ; Infusions, Intravenous ; Male ; Nepal ; Oxygen/blood ; Propanolamines/administration & dosage ; Receptors, Adrenergic, beta-1/metabolism ; Signal Transduction ; Time Factors ; Torsion Abnormality/diagnostic imaging ; Torsion Abnormality/etiology ; Torsion Abnormality/metabolism ; Torsion Abnormality/physiopathology ; Torsion, Mechanical ; Ventricular Dysfunction, Left/diagnostic imaging ; Ventricular Dysfunction, Left/etiology ; Ventricular Dysfunction, Left/metabolism ; Ventricular Dysfunction, Left/physiopathology ; Ventricular Function, Left ; Young Adult
Chemical Substances	ADRB1 protein, human ; Adrenergic beta-1 Receptor Antagonists ; Propanolamines ; Receptors, Adrenergic, beta-1 ; esmolol (MDY902UXSR) ; Oxygen (S88TT14065)
Language	English
Publishing date	2019-05-15
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2435045-X
ISSN	1942-0080 ; 1941-9651
ISSN (online)	1942-0080
ISSN	1941-9651
DOI	10.1161/CIRCIMAGING.118.008455
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Article ; Online: Acute mountain sickness in children at 4380 meters in the Himalayas.

Pradhan, Santosh / Yadav, Sanjay / Neupane, Pritam / Subedi, Prajan

Wilderness & environmental medicine

2009 Volume 20, Issue 4, Page(s) 359–363

Abstract: Objective: To determine the incidence of and risk factors for acute mountain sickness (AMS) in native Nepalese children during a pilgrimage trip to Gosaikunda Lake in the Langtang National Park Region of Nepal (elevation 4380 m).: Methods: A ... ...

Abstract	Objective: To determine the incidence of and risk factors for acute mountain sickness (AMS) in native Nepalese children during a pilgrimage trip to Gosaikunda Lake in the Langtang National Park Region of Nepal (elevation 4380 m). Methods: A descriptive, noninterventional, cross-sectional study was completed on a group of children during the pilgrimage to Gosaikunda. Participants were interviewed about the symptoms of AMS using the Lake Louise Scoring System. Results: Thirty-six children between 3 and 15 years of age were interviewed after a rapid ascent (over 1 to 3 days) from 1950 m to 4380 m. Acute mountain sickness was diagnosed in 17 of 36 (47.2%) children. The sickness was seen in only 5 of 20 (25%) children who took 2 or more days to ascend, compared with 12 of 16 (75%) children who spent only 1 night (reaching the study site at Gosaikunda on the second day) to complete the same ascent (P < or = .01, odds ratio [OR] = 9.0, 1.61 < OR < 57.36). No significant correlation was found between the incidence of AMS and gender, previous exposure to high altitude, or concurrent illness. Conclusions: Our results indicate that the incidence of AMS in this group of Nepalese children was high and associated with rapidity of ascent. Rapid ascent to high sleeping altitude and increased physical activity were observed as possible risk factors. We suggest organizing educational programs to make children and their parents aware of altitude-related problems and advise gradual ascent to such high-altitude pilgrimage sites.
MeSH term(s)	Adolescent ; Altitude ; Altitude Sickness/epidemiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Male ; Risk Factors
Language	English
Publishing date	2009
Publishing country	United States
Document type	Journal Article
ZDB-ID	1238909-2
ISSN	1545-1534 ; 1080-6032
ISSN (online)	1545-1534
ISSN	1080-6032
DOI	10.1580/1080-6032-020.004.0359
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Article ; Online: Clinical problem-solving. A creeping suspicion.

Rice, Casey M / Yadav, Siddhartha / Boyanton, Bobby / Subedi, Prajan / Band, Jeffrey

The New England journal of medicine

2014 Volume 371, Issue 1, Page(s) 68–73

MeSH term(s)	Acyclovir/therapeutic use ; Antiviral Agents/therapeutic use ; Aphasia/etiology ; Cerebrospinal Fluid/immunology ; Cerebrospinal Fluid/microbiology ; Colonic Neoplasms/complications ; Diagnosis, Differential ; Encephalitis, Herpes Simplex/complications ; Encephalitis, Herpes Simplex/diagnosis ; Encephalitis, Herpes Simplex/drug therapy ; Female ; Fever/etiology ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Polymerase Chain Reaction ; Simplexvirus/isolation & purification ; Spinal Puncture ; Temporal Lobe/microbiology ; Temporal Lobe/pathology
Chemical Substances	Antiviral Agents ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2014-07-03
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcps1212310
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Article ; Online: Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m.

Willie, Christopher K / Patrician, Alexander / Hoiland, Ryan L / Williams, Alexandra M / Gasho, Christopher / Subedi, Prajan / Anholm, James / Drane, Aimee / Tymko, Michael M / Nowak-Flück, Daniela / Plato, Sawyer / McBride, Emily / Varoli, Giovanfrancesco / Binsted, Gordon / Eller, Lindsay K / Reimer, Raylene A / MacLeod, David B / Stembridge, Michael / Ainslie, Philip N

The Journal of physiology

2021 Volume 599, Issue 5, Page(s) 1685–1708

Abstract: Key points: Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders ... ...

Abstract	Key points: Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders during either (1) ascent to high altitude, or (2) following partial acclimatization, when compared to high-altitude adapted Sherpa. During ascent to 5050 m, the rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders; however, upon arrival to 5050 m, PASP levels were comparable in both groups, but the reduction in iron bioavailability was more prevalent in lowlanders compared to Sherpa. Following partial acclimatization to 5050 m, there were differential influences of iron status manipulation (via iron infusion or chelation) at rest and during exercise between lowlanders and Sherpa on the pulmonary vasculature. Abstract: To examine the adaptational role of iron bioavailability on the pulmonary vascular responses to acute and chronic hypobaric hypoxia, the haematological and cardiopulmonary profile of lowlanders and Sherpa were determined during: (1) a 9-day ascent to 5050 m (20 lowlanders; 12 Sherpa), and (2) following partial acclimatization (11 ± 4 days) to 5050 m (18 lowlanders; 20 Sherpa), where both groups received an i.v. infusion of either iron (iron (iii)-hydroxide sucrose) or an iron chelator (desferrioxamine). During ascent, there were reductions in iron status in both lowlanders and Sherpa; however, Sherpa appeared to demonstrate a more efficient capacity to mobilize stored iron, compared to lowlanders, when expressed as a Δhepcidin per unit change in either body iron or the soluble transferrin receptor index, between 3400-5050 m (P = 0.016 and P = 0.029, respectively). The rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders during ascent; however, PASP was comparable in both groups upon arrival to 5050 m. Following partial acclimatization, despite Sherpa demonstrating a blunted hypoxic ventilatory response and greater resting hypoxaemia, they had similar hypoxic pulmonary vasoconstriction when compared to lowlanders at rest. Iron-infusion attenuated PASP in both groups at rest (P = 0.005), while chelation did not exaggerate PASP in either group at rest or during exaggerated hypoxaemia (
MeSH term(s)	Acclimatization ; Altitude ; Humans ; Hypoxia ; Iron ; Vasoconstriction
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2021-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP281114
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Article ; Online: Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

Vermeulen, Tyler D / Boulet, Lindsey M / Stembridge, Mike / Williams, Alexandra M / Anholm, James D / Subedi, Prajan / Gasho, Chris / Ainslie, Philip N / Feigl, Eric O / Foster, Glen E

American journal of physiology. Heart and circulatory physiology

2018 Volume 315, Issue 1, Page(s) H132–H140

Abstract: It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial ... ...

Abstract	It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po
MeSH term(s)	Adrenergic beta-Antagonists/pharmacology ; Adult ; Blood Flow Velocity ; Blood Pressure ; Carbon Dioxide/metabolism ; Coronary Vessels/drug effects ; Coronary Vessels/physiology ; Heart Rate ; Humans ; Male ; Myocardium/metabolism ; Oxygen/metabolism ; Oxygen Consumption ; Propanolamines/pharmacology ; Vasodilation ; Ventricular Function, Left
Chemical Substances	Adrenergic beta-Antagonists ; Propanolamines ; Carbon Dioxide (142M471B3J) ; esmolol (MDY902UXSR) ; Oxygen (S88TT14065)
Language	English
Publishing date	2018-03-30
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00689.2017
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Article ; Online: The independent effects of hypovolaemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800 m.

Stembridge, Mike / Ainslie, Philip N / Boulet, Lindsey M / Anholm, James / Subedi, Prajan / Tymko, Michael M / Willie, Christopher K / Cooper, Stephen-Mark / Shave, Rob

The Journal of physiology

2018 Volume 597, Issue 4, Page(s) 1059–1072

Abstract: Key points: We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed ... ...

Abstract	Key points: We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed echocardiography and maximal exercise tests at sea level (344 m), and following 5-10 days at the Barcroft Laboratory (3800 m; White Mountain, California) with and without (i) plasma volume expansion to sea level values and (ii) administration of the pulmonary vasodilatator sildenafil in a double-blinded and placebo-controlled trial. The high altitude-induced reduction in LV filling and ejection was abolished by plasma volume expansion but to a lesser extent by sildenafil administration; however, neither intervention had a positive effect on maximal exercise capacity. Both hypovolaemia and hypoxic pulmonary vasoconstriction play a role in the reduction of LV filling at 3800 m, but the increase in LV filling does not influence exercise capacity at this moderate altitude. Abstract: We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5-10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.
MeSH term(s)	Acclimatization ; Adult ; Altitude ; Diastole ; Exercise Tolerance ; Humans ; Hypovolemia/physiopathology ; Hypoxia/physiopathology ; Lung/blood supply ; Lung/physiology ; Lung/physiopathology ; Male ; Pulmonary Artery/drug effects ; Pulmonary Artery/physiology ; Pulmonary Artery/physiopathology ; Sildenafil Citrate/pharmacology ; Vasoconstriction ; Vasodilator Agents/pharmacology ; Ventricular Function
Chemical Substances	Vasodilator Agents ; Sildenafil Citrate (BW9B0ZE037)
Language	English
Publishing date	2018-06-06
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP275278
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Article ; Online: Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans.

Hoiland, Ryan L / Bain, Anthony R / Tymko, Michael M / Rieger, Mathew G / Howe, Connor A / Willie, Christopher K / Hansen, Alex B / Flück, Daniela / Wildfong, Kevin W / Stembridge, Mike / Subedi, Prajan / Anholm, James / Ainslie, Philip N

Journal of applied physiology (Bethesda, Md. : 1985)

2017 Volume 122, Issue 4, Page(s) 795–808

Abstract: Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, ...

Abstract	Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]), ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), CBF (duplex ultrasound), and intracranial blood velocities (transcranial Doppler ultrasound) were measured during 5-min stages of isocapnic hypoxia at sea level (98, 90, 80, and 70% [Formula: see text]). Ventilation, [Formula: see text] and [Formula: see text], blood pressure, heart rate, and CBF were also measured upon exposure (128 ± 31 min following arrival) to high altitude (3,800 m) and 6 h following theophylline administration. At sea level, although the CBF response to hypoxia was unaltered pre- and postplacebo, it was reduced following theophylline (
Language	English
Publishing date	2017-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00840.2016
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