Pharmacologically increasing cerebral blood flow reduced central sleep apnea severity at high altitude

Background: Exposure to very high altitudes causes central sleep apnea (CSA). We have previously shown that increasing cerebral blood flow (CBF) by iv acetazolamide (acet) reduced CSA severity by ∼ 50%; however, this effect was confounded by a rise in PaCO 2 of ∼ 3 mmHg. Aim: To study the effects of increasing CBF on CSA without altering PaCO 2 . Methods: At 5050m (The Pyramid, Lobuje, Nepal), 12 subjects (9M, 3F; aged 32±7 y) completed awake ventilatory response testing pre and post injection of either iv acet (10mg/kg) combined with dobutamine (dob) (2-5ug/kg/min) or placebo injections. Immediately following drugs / placebo, CBF measurements and ventilatory response testing were made, and subjects underwent full polysomnography monitored sleep while the pharmacological (dob) intervention was maintained. Arterial blood gas samples were collected and ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) were measured. Duplex ultrasound of blood flow in the internal carotid and vertebral arteries was used to estimate global CBF. Results: Iv acet/dob increased global CBF by 34% compared to placebo (P 2 , PaO 2 and pH were all unchanged. Conclusion: Pharmacologically increasing CBF without alteration of arterial blood gas tensions markedly reduced the severity of central sleep apnea at high altitude, possibly by reducing HCVR. Supported by Peninsula Health Care Pty Ltd, NSERC, CRC and Lottery Health NZ. Research conducted under the memorandum between Nepal Health Research Council and EVK2-CNR.