Splanchnic organ adenine nucleotides and their metabolites in haemorrhagic shock

Cunningham, S. K.; Keaveny, T. V.

doi:10.1007/bf03030948

Cited by 31 publications

(15 citation statements)

References 24 publications

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“…Berne and Rubio (42) were interested mainly in studying the effect of adenosine on the circulation. Since then other groups have reported high hypoxanthine concentrations in hypoxic tissues including kidney (43), liver (44), brain (44)(45)(46), myocardium (44,47), intestine (48), lungs (49), and placenta (50). In placental tissue the hypoxanthine concentration was correlated with the energy charge and a negative correlation of 0.79 was found (50).…”

Section: Studies On Isolated Organsmentioning

confidence: 96%

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

Saugstad¹

1988

Pediatr Res

379

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: Studies On Isolated Organsmentioning

confidence: 96%

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

Saugstad¹

1988

Pediatr Res

379

206

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“…216 ATP may prevent disruption of glucose homeostasis and development of endotoxin shock by counteracting insulin and blunting hypoglycemia. It was claimed that treatment of shocked animals with ATP-MgCl 2 is an effective therapy for experimental hemorrhagic shock although this has been debated.…”

Section: Sepsis and Septic Shockmentioning

confidence: 99%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

339

295

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Abstract:There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y 1 , P2Y 12 , and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine. (Circ Res. 2017;120:207-228.

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“…An early theory was that degradation of adenine nucleotides is related to irreversibility in hemorrhagic shock, and a marked reduction in ATP contents of the pancreas, liver, and duodenum was demonstrated (Cunningham and Keaveny, 1977). It was suggested that ATP prevented disruption of glucose homeostasis and development of endotoxin shock by counteracting insulin and blunting hypoglycemia (Chaudry et al, 1976;Filkins and Buchanan, 1977).…”

Section: G Sepsis and Septic Shockmentioning

confidence: 99%