ExtractThe hypoxanthine concentration in plasma was found to be a sensitive parameter of hypoxia of the fetus and the newborn infant.The plasma level of hypoxanthine in the umbilical cord in 29 newborn infants with normal delivery varied between 0 and 11.0 pmol/liter with a mean of 5.8 pmollliter, SD 3.0 pmol/liter.Compared with this reference group the hypoxanthine concentration in ~l a s m a of the umbilical cord in 10 newborn infants with clinical signs of intrauterine hypoxia during labor was found to be significantly higher, with a range of 11.0-61.5 pmol/liter, with a mean of 25.0 pmol/liter, SD 18.0 pmollliter.The plasma level of hypoxanthine in two premature babies developing an idiopatic respiratory distress syndrome was monitored. The metabolite was found to be considerably increased, in one of them more than 24 hr after a period of hypoxia necessitating artificial ventilation.The hypoxanthine level in plasma of umbilical arterial blood was followed about 2 hr postpartum in three newborn infants with clinical signs of intrauterine hypoxia. The decrease of the plasma concentration of the metabolite seemed to be with a constant velocity, as it was about 10 pmol/liter/hr in these cases.A new method was used for the determination of hypoxanthine in plasma, based on the principle that POz decreased when hypoxanthine is oxidized to uric acid.
SpeculationThese preliminary results indicate that the hypoxanthine concentration in plasma is a sensitive parameter of hypoxia. It is expected that this metabolite will express the degree of hypoxia quantitatively and regardless of the etiology of the hypoxia. The excretion of hypoxanthine and other purine metabolites in urine might also have diagnostic value.It has been known for more than 40 years that the concentration of uric acid in plasma and its excretion in the urine is increased during anaerobic conditions (12). Berne (2) found that there was an increased liberation of inosine and hypoxanthine into the coronary circulation when the myocardium of cat and dog was ischemic. Crowell et al. (6) showed that in hemorrhagic shock there was an increased catabolism of high energy purines to uric acid. During the past years a series of other papers have confirmed these results (1,5,13). Figure 1 describes schematically the purine catabolism from AMP (modified from Cantarow and Schepartz (4)). As oxygen is needed for the transformation of hypoxanthine into uric acid, the reaction will probably be slowed down when the availability of oxygen is reduced. Hence we can imagine that during hypoxia there will be accumulation of hypoxanthine.Lack of oxygen will of course slow down the oxidative 15 phosphorylation, and the concentration of AMP will increase. From the chemical equilibria it can be deduced that an increased AMP concentration, as in hypoxia, will also lead to an increased degradation of AMP, and consequently an increased production of inter alia hypoxanthine. It is also known that xanthine oxidase is inhibited during hypoxia (3). This too will in turn be followed by...