Ventilatory response to sustained hypoxia after pretreatment with aminophylline

During sustained hypoxia the decline in ventilation that occurs in normal adult humans may be related to central accumulation of a neurochemical with net inhibitory effect. Recent investigations have shown that the putative neurotransmitter adenosine can effect a prolonged respiratory inhibition. Therefore we evaluated the possible role of adenosine in the hypoxia ventilatory decline by employing aminophylline as an adenosine blocker. We evaluated the ventilatory response to 25 min of sustained hypoxia (80% arterial O2 saturation), in eight young adults after pretreatment with either intravenous saline or aminophylline. With a mean serum aminophylline level of 15.7 mg/l, over 25 min of sustained hypoxia, peak hypoxic ventilation decreased by only 12.8% compared with 24.8% with saline, a significant difference. However, the ventilatory decline during sustained hypoxia was not abolished by the aminophylline pretreatment. Unlike the usual tidal volume-dependent attenuation of hypoxic ventilation exhibited after saline, after aminophylline the ventilatory decline was achieved predominantly through alterations in respiratory timing. Thus aminophylline pretreatment did alleviate the hypoxic ventilatory decline, although the associated alterations in breathing pattern were uncharacteristic. We conclude that adenosine may play a contributing role in the hypoxic ventilatory decline.