Diverse effects of the nucleoside adenosine have been reported including stimulation of respiration in man. This thesis discusses the results of studies undertaken to further characterise the respiratory and concomitant cardiovascular effects of infusion of adenosine in man.
In healthy volunteers intravenous infusion of adenosine, but not its first metabolite inosine, caused a dose -related increase in minute ventilation, not due to hypotension or bronchoconstriction, and a fall in end-tidal carbon dioxide tension.
The increase in minute ventilation was largely due to an increase in tidal volume (VT). Inspiratory duration (T1) was unchanged but expiratory duration was slightly reduced. Mean inspiratory flow (VT /TI) was increased as was functional residual capacity (FRC). These changes are similar to those that have been reported during equivalent ventilatory stimulation by hypoxia and hypercapnia.
Adenosine caused various symptoms including discomfort in the epigastrium, chest and jaw, flushing, dyspnoea and paraesthesiae, which limited the maximum dose.
Aminophylline antagonised the adenosine - induced increases in ventilation, heart rate and systolic blood pressure and reduced the symptoms, suggesting that these effects are mediated by cell- surface receptors. The venous plasma concentration of adenosine only increased at the higher maximum dose possible after aminophylline, consistent with the very short half -life of adenosine as determined in vitro.
Three studies were performed in patients undergoing diagnostic cardiac catheterisation. In one study infusion of adenosine into the aorta proximal to the head and neck vessels caused respiratory stimulation whereas infusion into the upper descending thoracic aorta did not, although chest and epigastric discomfort were more common. Since in animals adenosine depresses respiration within the central nervous system, this study supports the suggestion that adenosine may stimulate respiration by an action within the carotid bodies. Furthermore it suggests that the respiratory stimulation is not primarily due to symptoms caused by adenosine.
In a second study the mean plasma adenosine concentration in the upper descending thoracic aorta increased from 0.07 μM at baseline to 1.2 μM during iv infusion at the maximum dose. Since micromolar concentrations may be achieved in tissues during hypoxia, due to hydrolysis of adenine nucleotides, these results are consistent with the suggestion that adenosine might participate in the ventilatory response to hypoxia. An unexpected finding was that respiration increased in 3 of the 7 patients before the adenosine concentration did. Since adenosine has a half -life of only a few seconds this finding is consistent with a more proximal effect of adenosine, e.g. within the lungs.
In a third study, which investigated its haemodynamic effects, adenosine increased cardiac output and caused pulmonary and systemic vasodilation. The pulmonary vasodilation first developed at a dose which did not affect systemic vascular resistance suggesting that at low dose (< 60 μg /kg /min) adenosine might be useful as a selective pulmonary vasodilator. Higher doses produced an increase in left ventricular end -diastolic pressure of uncertain cause.
Adenosine caused variable effects in 6 patients with chronic hypoxia due to obstructive airways disease. Four showed a slight increase in minute ventilation and improvement in arterial blood gas tensions. None developed worse spirometry but all showed an increase in FRC which was greatest in 2 patients whose tidal volume and arterial oxygen tension fell, suggesting that the changes in lung volume were disadvantageous.
