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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.

Original publication

DOI

10.1042/CS20050036

Type

Journal article

Journal

Clin Sci (Lond)

Publication Date

09/2005

Volume

109

Pages

319 - 324

Keywords

Acclimatization, Adult, Aged, Altitude, Blood Pressure, Cerebrovascular Circulation, Heart Rate, Humans, Male, Middle Aged, Oxygen, Oxygen Consumption, Phosphodiesterase Inhibitors, Piperazines, Purines, Sildenafil Citrate, Sulfones, Vasodilator Agents