Ratio of the concentration of hypoxanthine to creatinine in urine from newborn infants: a possible indicator for the metabolic damage due to hypoxia

Harkness, R. A.; Simmonds, R. J.; Coade, S. B.; Lawrence, Catherine R

doi:10.1111/j.1471-0528.1983.tb08942.x

Cited by 18 publications

(6 citation statements)

References 19 publications

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“…After this period the hypoxanthine concen- In newborn infants the urinary hypoxanthine excretion during the first 24 h of life is three to four times higher in babies suffering from intrauterine hypoxia compared with nonhypoxic babies (78). There was also a high correlation between the urinary hypoxanthine excretion and the hypoxanthine/creatinine ratio in the urine (r = 0.70) (79). Such a ratio can be determined on random urine samples, simplifying the collection of urine.…”

Section: Animal Studiesmentioning

confidence: 99%

“…Even on the 2nd day of life an elevated ratio was found in babies with intrauterine hypoxia. Infants who are neurologically abnormal more than 48 h postpartum have a higher hypoxanthine/creatinine ratio than hypoxic infants who subsequently developed normally (79,80). In adult patients resuscitated after cardiac arrest, urinary excretion of hypoxanthine increased 6-fold the first 2 h after the cardiac arrest (8 1).…”

Section: Animal Studiesmentioning

confidence: 99%

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Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Saugstad¹

1988

Pediatr Res

374

206

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Hypoxia is a common insult during the perinatal and neonatal period. New and better ways to evaluate hypoxia are needed. In 1975 we demonstrated high concentrations of the purine metabolite hypoxanthine in umbilical cord plasma after intrauterine hypoxia and proposed that hypoxanthine could be used as an indicator of hypoxia (1). Since then a large number of studies have been published dealing with different aspects of hypoxanthine in hypoxia. However, investigators in this field have encountered several methodologic problems: 1) Hypoxanthine leaks rapidly from erythrocytes (2, 3); if plasma is not separated promptly from red cells, falsely elevated plasma hypoxanthine concentrations will be found. 2) There are large variations in purine metabolism among species. 3) No clear definition of clinical hypoxia is available. Many authors do not distinguish between the terms hypoxemia and hypoxia, which adds to the confusion. We define tissue hypoxia as: "oxygen deficiency resulting in altered or interrupted energy metabolism" (4). It is important to be aware that hypoxia has two stages. In the first stage it is compensated because the cells are able to meet energy demands through anaerobic metabolism and other mechanisms. (We are not dealing with physiologic adaptation to hypoxia.) In the second stage of hypoxia or uncompensated hypoxia, energy demands are not met and cell injury ensues. At present there are no techniques for distinguishing between these two stages in clinical medicine, and such a distinction would be useful. Theoretically hypoxanthine should only be elevated in uncompensated hypoxia, while pH and lactate changes occur in compensated hypoxia. It seems, however, that hypoxanthine is also elevated to some extent in uncompensated hypoxia.Renewed interest in hypoxanthine developed when it was realized that hypoxanthine is a potential free radical generator (5, 6). Hypoxanthine seems to play a role in posthypoxic reoxygenation cell injury through oxygen radical production (7) and is therefore involved in the pathogenesis of a number of diseases. Hypoxanthine also modulates a number of other processes because it reacts with benzodiazepine receptors (8) and inhibits phosphodiesterase in the brain (9). Hypoxanthine inhibits the effect of several cytotoxic drugs and may therefore influence treatment with such drugs (10).Herein we summarize the extensive literature on hypoxanthine published during the last decade and try to answer the question: How useful in clinical medicine are hypoxanthine measurements in plasma and other body fluids? Is hypoxanthine a better marker of hypoxia than lactate or pH? Further, we discuss the significance of hypoxanthine as a potential oxygen radical generator and put forward a hypothesis for the pathogenesis of an "oxygen radical disease in neonatology". In hypoxia there is an accelerated breakdown of AMP to hypoxanthine. Figure 1 illustrates several important aspects of hypoxanthine metabolism in hypoxia. Normally about 90% of the hypoxanthine formed is reutilized through the sa...

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Section: Animal Studiesmentioning

confidence: 99%

Section: Animal Studiesmentioning

confidence: 99%

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Saugstad¹

1988

Pediatr Res

374

206

View full text Add to dashboard Cite

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“…HARKNESS et al [7] found a significant correlation (r = 0.70, p < 0.001) between urinary Hyp excretion and Hyp/creatinine ratio in samples from infants with clinical evidence of intrapartum asphyxia. This situation, however, is quite different from the situation in our study, where samplings were made during hypoxemia.…”

Section: Discussionmentioning

confidence: 97%

Plasma hypoxanthine reacts more abruptly to changes in oxygenation than base deficit and uric acid in newborn piglets

Almaas¹,

Sundar²,

Rootwelt³

et al. 1997

Jpme

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Previously, high postmortem concentrations of hypoxanthine have been found in vitreous humor of children dying from sudden infant death syndrome (SIDS). We wanted to investigate further the accumulation of hypoxanthine in vitreous humor during hypoxia. Twenty-four piglets aged 9-15 days were exposed to continuous hypoxemia (180 min 11% O2, n = 6), long interval intermittent hypoxemia (60 min 11% O2, 20 min room air, n = 7) or short interval intermittent hypoxemia (10 min 9% O2, 10 min room air with (n = 6) or without (n = 5) superimposed ligation of both carotid arteries). The increase in vitreous humor Hyp was four-fold higher (p < 0.01) with ligation of the carotid arteries (14 +/- 2.4 to 38 +/- 8.9 mumol/l) than without ligation (15 +/- 2.8 to 21 +/- 5.9 mumol/l). During continuous hypoxemia, plasma Hyp (r = 0.85), Xa (r = 0.89) uric acid (UA) (r = 0.85), and base deficit (BD) (r = 0.78) increased almost linearly (p < 0.001). Plasma Hyp responded more abruptly to changes in oxygenation than base deficit (BD) and UA. Ligation of the carotid arteries had a strong impact on Hyp accumulation in vitreous humor, suggesting that vitreous humor Hyp is not merely a filtration product of plasma Hyp, but reflects local hypoxia/ischemia in the eye.

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“…Hypoxanthine concentration in urine at 24 h post-partum was found to be 3-4 times higher in neonates who had suffered intrauterine hypoxia than in the control group [124]. Harkness et al [125] observed that neonates with perinatal hypoxia who developed neurologic anomalies after 48 h post-partum showed a higher hypoxanthine: creatinine ratio than those who did not develop neurologic anomalies [125].…”

Section: Hypoxanthine and Xanthinementioning

confidence: 99%

Biochemical parameters predictive of neuronal damage in children with neonatal hypoxic ischemia

Castro-Gago

2015

J Pediatr Neurol

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On the basis of the physiopathological mechanisms involved in the brain damage related to hypoxic-ischemic encephalopathy of the newborn, a number of metabolic parameters have been studied with the aim to provide an early and reliable marker of tissue injury for diagnostic and prognostic purpose. Some authors have even suggested that biochemical indicators may be more effective than the results of clinical, Apgar score, pH in cord blood, electroencephalographic and neuroimaging data. In the present review, we discuss the diagnostic and prognostic value of a series of biochemical parameters, with special reference to the diagnosis of neonatal hypoxic-ischemic encephalopathy. For methodological purpose the exposition is structured in the following sections: creatine kinase isoenzymes; lactate; lactate dehydrogenase, aspartate aminotransferase and hydroxibutirate dehydrogenase; excitatory amino acids; glial fibrillary acidic protein; cytokines; neuron-specific enolase; oxypurines; cyclic adenosine monophosphate; and others. The current role of the above mentioned biochemical parameters as predictors of brain damage and the future perspectives on this topic are discussed.

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Ratio of the concentration of hypoxanthine to creatinine in urine from newborn infants: a possible indicator for the metabolic damage due to hypoxia

Cited by 18 publications

References 19 publications

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Hypoxanthine as an Indicator of Hypoxia: Its Role in Health and Disease through Free Radical Production

Plasma hypoxanthine reacts more abruptly to changes in oxygenation than base deficit and uric acid in newborn piglets

Biochemical parameters predictive of neuronal damage in children with neonatal hypoxic ischemia

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