Document Detail


Effect of sildenafil and acclimatization on cerebral oxygenation at altitude.
MedLine Citation:
PMID:  15865603     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 2 h], 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.
Authors:
Colin W M Chan; Helen Hoar; Kyle Pattinson; Arthur R Bradwell; Alexander D Wright; Christopher H E Imray;
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  109     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-17     Completed Date:  2005-12-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  319-24     Citation Subset:  IM    
Affiliation:
Immunodiagnostics Research Laboratory, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK. colin.chan@mac.com
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MeSH Terms
Descriptor/Qualifier:
Acclimatization / physiology*
Adult
Aged
Altitude*
Blood Pressure / drug effects
Cerebrovascular Circulation / drug effects*
Heart Rate / drug effects
Humans
Male
Middle Aged
Oxygen / blood
Oxygen Consumption / drug effects
Phosphodiesterase Inhibitors / pharmacology*
Piperazines / pharmacology*
Purines
Sulfones
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 0/Vasodilator Agents; 139755-83-2/sildenafil; 7782-44-7/Oxygen

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