Andrew H. Watt

Plasma adenosine concentrations during adenosine-induced respiratory stimulation in man

SummaryIntravenous infusion of the nucleoside adenosine stimulates respiration, probably at least partly by an action in the carotid bodies, and also potentiates the ventilatory response to hypoxia, suggesting that it might be involved in the control of breathing.Whether the effects of adenosine occur at concentrations likely to be achieved in vivo is unknown and was investigated in 7 patients with arterial catheters inserted for diagnostic purposes.During intravenous infusion of adenosine (Maximum dose per min: mean 130 μg kg−1) mean minute ventilation increased from 5.5 to 10.9 l min−1 while mean plasma adenosine concentration in the aortic arch increased from 0.07 to 1.2 μM. In 3 patients ventilation first increased without a detectable increase in aortic adenosine concentration, suggesting a possible intra-pulmonary effect of adenosine, although increased concentrations were apparent at higher doses.Micromolar concentrations of adenosine are probably achieved in vivo in tissues during hypoxia. The present results show that at such concentrations adenosine stimulates respiration and are consistent with the suggestion that adenosine release may mediate or modulate the ventilatory response to hypoxia. A possible intra-pulmonary effect of adenosine merits further study.

Effect of aminophylline on the respiratory depressant action of intravenous adenosine in neonatal rabbits

We administered intravenous adenosine to 11 neonatal rabbits. Adenosine depressed respiration in 10 of 11 rabbits. For the group as a whole the adenosine-induced respiratory depression was highly significant (p less than 0.001). After aminophylline administration to the same animals the respiratory effect of intravenous adenosine was abolished in 3 animals. In 7 animals the effect of adenosine was reversed and respiratory stimulation was observed. After aminophylline adenosine produced a significant (p less than 0.001) increase in respiration in the group studied. The alteration of responses to intravenous adenosine by aminophylline in neonatal rabbits is similar to the effect of aminophylline on respiratory responses to hypoxia in neonates. Such an effect of aminophylline and other methylxanthines on adenosine actions, possibly central in site may explain their beneficial effect in the treatment of apnoea in the human neonate.

Comparison of respiratory effects of intravenous adenosine in neonatal and adult rabbits

We administered adenosine by repeated intravenous bolus doses to 34 neonatal rabbits in a dose of 120 micrograms X kg-1 (which we had previously found to stimulate respiration in adult rabbits). In 13 neonatal animals adenosine produced transient respiratory depression. In 15 neonatal animals the change in respiration in response to adenosine did not reach statistical significance. In two animals a transient increase in respiration occurred in response to adenosine. In the neonatal group as a whole intravenous adenosine significantly depressed ventilation. In eleven of the animals studied as neonates, respiratory responses to adenosine were again studied in adulthood. In 10 animals respiratory stimulation occurred in response to adenosine. In the adult group adenosine significantly increased ventilation, in contrast to its effects in the neonatal group. The respiratory effects of intravenous adenosine have not been previously described in neonatal animals. Respiratory stimulation produced by intravenous adenosine in adult rabbits contrasts with the respiratory depression commonly seen in neonatal rabbits in this study. It is suggested that altered responses to adenosine may be involved in the difference between the ventilatory response to hypoxia in adult and neonatal animals.