Phosphodiesterase-5 inhibitors decrease hypoxic pulmonary vasoconstriction under hypobaric hypoxia, but are not known to affect cerebral blood flow or oxygenation. The present study was designed to evaluate the effect of sildenafil on cerebral haemodynamics during acute exposure to altitude and after acclimatization. Ten subjects were studied 1 and 3 days after rapid ascent to 3480 m before and for two consecutive hours after taking sildenafil (50 mg). Before acclimatization, HR (heart rate) rose at 1 h (76.3±1.0 beats/min compared with 72.5±1.5 beats/min at baseline; P<0.05) and had returned to baseline at 2 h (71.3±1.1 beats/min; P>0.05). Mean BP (blood pressure) fell from 96.0±2.0 mmHg at baseline to 91.7±2.5 (P<0.001) at 1 h and 89.8±1.8 mmHg (P<0.0001) at 2 h, whereas SaO2 (arterial oxygen saturation) increased from 83.9±0.5% at baseline to 85.3±0.4% (P<0.0001) at 1 h and 85.0±0.5% (P<0.01) at 2 h. MCAV [MCA (middle cerebral artery) velocity] and PETCO2 (end-tidal partial pressure of CO2) were unchanged, but rSO2 (regional cerebral oxygen saturation) rose progressively at 1 h (62.7±0.8%; P<0.05) and 2 h (65.3±0.9%; P<0.0001) compared with baseline (59.3±1.3%). After 3 days of acclimatization, resting rSO2 and RMCA (MCA resistance) increased and oxygen delivery fell. Changes in HR and mean BP after sildenafil were similar to day 1, but SaO2 did not change. However, rSO2 increased [61.7±0.9% at baseline to 65.0±1.0% (P<0.0001) at 1 h and 64.0±0.9% (P<0.001) at 2h], despite a reduction in MCAV [65.3±1.8 cm/s at baseline to 61.3±1.5 cm/s (P<0.01) at 1 h and 60.9±1.7 cm/s (P<0.0001) at 2 h] and PETCO2 [4.1±0.05 kPa at baseline to 4.0±0.04 kPa at 2 h (P<0.01)]. These observations suggest that sildenafil improves cerebral oxygenation at altitude. Whereas the early changes before acclimatization may be largely pulmonary in origin, the later observations may be a direct cerebral effect which warrants further study.
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Research Article|
August 24 2005
Effect of sildenafil and acclimatization on cerebral oxygenation at altitude
Colin W. M. Chan;
*Immunodiagnostics Research Laboratory, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, U.K.
Correspondence: Dr Colin W. M. Chan (email [email protected]).
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Helen Hoar;
Helen Hoar
*Immunodiagnostics Research Laboratory, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, U.K.
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Kyle Pattinson;
Kyle Pattinson
†Nuffield Department of Anaesthetics, University of Oxford, The John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, U.K.
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Arthur R. Bradwell;
Arthur R. Bradwell
*Immunodiagnostics Research Laboratory, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, U.K.
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Alexander D. Wright;
Alexander D. Wright
*Immunodiagnostics Research Laboratory, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, U.K.
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Christopher H. E. Imray;
Christopher H. E. Imray
‡County Vascular Unit, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, U.K.
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Expeditionary Society the Birmingham Medical Research
Expeditionary Society the Birmingham Medical Research
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Publisher: Portland Press Ltd
Received:
January 26 2005
Revision Received:
April 05 2005
Accepted:
May 03 2005
Accepted Manuscript online:
May 03 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 109 (3): 319–324.
Article history
Received:
January 26 2005
Revision Received:
April 05 2005
Accepted:
May 03 2005
Accepted Manuscript online:
May 03 2005
Citation
Colin W. M. Chan, Helen Hoar, Kyle Pattinson, Arthur R. Bradwell, Alexander D. Wright, Christopher H. E. Imray, Expeditionary Society the Birmingham Medical Research; Effect of sildenafil and acclimatization on cerebral oxygenation at altitude. Clin Sci (Lond) 1 September 2005; 109 (3): 319–324. doi: https://doi.org/10.1042/CS20050036
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