Clinical Science (2005) 109, 319-324 - C.W.M. Chan and others

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Clinical Science (2005) 109, (319–324) (Printed in Great Britain)

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Effect of sildenafil and acclimatization on cerebral oxygenation at altitude

Colin W. M. CHAN*, Helen HOAR*, Kyle PATTINSON†, Arthur R. BRADWELL*, Alexander D. WRIGHT*, Christopher H. E. IMRAY‡ and the Birmingham Medical Research Expeditionary Society*

*Immunodiagnostics Research Laboratory, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, U.K., †Nuffield Department of Anaesthetics, University of Oxford, The John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, U.K., and ‡County Vascular Unit, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, U.K.

Key words: acclimatization, altitude, cerebral regional oxygen saturation, hypoxia, middle cerebral artery velocity, phosphodiesterase-5, sildenafil (Viagra®).

Abbreviations: AMS, acute mountain sickness; BP, blood pressure; DO₂, oxygen delivery; HR, heart rate; MCA, middle cerebral artery; MCAV, MCA velocity; NIRS, near-IR spectroscopy; NO, nitric oxide; eNOS, endothelial NO synthase; PDE5, phosphodiesterase-5; PETCO₂, end-tidal partial pressure of CO₂; R_MCA, MCA resistance; rSO₂, regional cerebral oxygen saturation; SaO₂, arterial oxygen saturation.

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 R_MCA (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.