Responses of the ischemic myocardium to allopurinol

DeWall, Richard A.; Vasko, Kent A.; Stanley, Edwin L.; Kezdi, Paul

doi:10.1016/0002-8703(71)90302-4

Cited by 178 publications

(35 citation statements)

References 15 publications

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“…Allopurinol, a structural analogue of hypoxanthine and a xanthine oxidase inhibitor, has been utilized experimentally in the attenuation of warm and cold ischemia and reperfusion injury of various organs since 1971 [1]. Initial studies on hemorrhagic shock in 1969 analyzed the effect that this drug had on the potential loss of functional purine bases during hypoxia-related events [2].…”

Section: Introductionmentioning

confidence: 99%

“…It was their hypothesis that xanthine oxidase prevented the irreversible breakdown of purine substrates that could be used for ATP re-synthesis after the ischemic insult [2]. As early as 1971, the effect of allopurinol in ischemic tissues was tested, starting with the ischemic myocardium by DeWall and group [1]. In 1972, Vasko et al [20] demonstrated the protective effect of allopurinol in renal ischemia.…”

Section: Introductionmentioning

confidence: 99%

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Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion

Peglow

Toledo

Anaya-Prado³

et al. 2010

J Hepato Biliary Pancreat

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Introduction Allopurinol was first introduced, in 1963, as a xanthine oxidase inhibitor when it was investigated for concomitant use with cancer chemotherapy drugs. Today it is used in gout and hyperuricemia. Due to its additive benefit in preventing oxidative damage, attention has shifted towards the use of allopurinol in organ ischemia and reperfusion. Current status Currently, the mechanism by which allopurinol exerts a protective benefit in ischemia reperfusion related events is not fully understood. There are various theories: it may act by inhibiting the irreversible breakdown of purine substrates, and/or by inhibiting the formation of reactive oxygen species, and/or by protecting against damage to the mitochondrial membrane. Aim This work focuses on liver ischemia and reperfusion injury in an effort to better understand the mechanisms associated with allopurinol and with this pathological entity. Review of literature The current research, mainly in animal models, points to allopurinol having a protective benefit, particularly if used pre‐ischemically in liver ischemia reperfusion injury. Furthermore, after reviewing allopurinol dosing and administration, it was found that 50 mg/kg is statistically the most effective dose in attenuating liver ischemia reperfusion injury. Owing to the limited number of samples, the time of administration did not show statistical difference, but allopurinol was often beneficial when given around 1 h before ischemia. Conclusion In conclusion, allopurinol, through its known xanthine oxidase inhibitory effect, as only one of the potential mechanisms, has demonstrated its potential application in protecting the liver during ischemia and reperfusion.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion

Peglow

Toledo

Anaya-Prado³

et al. 2010

J Hepato Biliary Pancreat

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“…The protective effects ofthe xanthine oxidase inhibitor allopurinol, in ischaemia, have been ascribed to its ability to preserve the tissue levels of high energy adenine nucleotides, such as ATP, during the ischaemia, and therefore prevent tissue damage, and loss of function (De Wall et al, 1971;Hopkins et al, 1975;Cunningham & Keaveny, 1978). More recently it has been suggested that the inhibition of xanthine oxidase can also reduce the formation of free radicals when molecular oxygen is abruptly restored to previously ischaemic tissues (i.e.…”

Section: Introductionmentioning

confidence: 99%

The protective action of allopurinol in an experimental model of haemorrhagic shock and reperfusion

Allan

Cambridge²,

Lee-Tsang-Tan

et al. 1986

British J Pharmacology

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Haemorrhagic shock was induced in anaesthetized, open‐chest dogs by controlled arterial bleeding, sufficient to reduce and maintain mean arterial blood pressure at 40 mmHg for 30 min. The blood volume was then restored to the pre‐shock level by rapid, intravenous reinfusion of the blood shed during the shock period. Haemorrhagic shock produced significant haemodynamic changes, characterized by a marked depression of myocardial function. Cardiac output (1226 ± 57 ml min−1), peak aortic blood flow (6030 ± 383 ml min−1) and maximum rate of rise of left ventricular pressure (2708 ± 264 mmHg s−1) were all reduced by more than 50%. The haemodynamic profile was markedly improved by reinfusion of shed blood but this improvement was not sustained. There was a gradual decline such that 50% of the untreated animals suffered complete circulatory collapse and death between 60 and 120 min following reinfusion. Neither haemorrhagic shock, nor reinfusion of shed blood produced any consistent or significant changes in the myocardial adenine nucleotide pool. The ATP, ADP and AMP levels were, respectively, 25.9 ± 4.2; 15.6 ± 1.0; 4.3 ± 1.9 nmol g−1 protein, before haemorrhagic shock; 21.6 ± 3.4; 21.5 ± 2.5; 10.2 ± 2.7 nmolg−1 protein, after 30min haemorrhagic shock; and 29.9 ± 3.9; 16.5 ±1.2; 4.2 ± 1.1 nmolg−1 protein, 60 min following reinfusion of shed blood. Pretreatment with allopurinol (50.0 mg kg−1 i.v.), 60 min before inducing haemorrhagic shock, had no significant effect upon the haemodynamic response to shock, but did prevent the gradual decline seen following reinfusion in the untreated animals. All of the allopurinol‐treated animals displayed significantly better haemodynamic profiles than the untreated animals, furthermore, there was a 100% survival rate in this group. Allopurinol had no significant effect upon the myocardial adenine nucleotide pool either during haemorrhagic shock or following reinfusion of shed blood.

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“…Active oxygen species, OZ or -OH, have been shown to play a role in the pathogenesis of ischemia-induced injury in a variety of different tissues [9][10][11]. DDC was dissolved in saline and injected subcutaneously into 24 h-fasted rats.…”

Section: Discussionmentioning

confidence: 99%

Ulcer Formation in Rat Stomach with Diethyldithiocarbamate

Oginö

Oka

Matsuura

et al. 1987

J. Clin. Biochem. Nutr.

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SummaryIt has been suggested that superoxide radicals play an important role in the pathogenesis of gastric mucosal lesions after ischemia. To prove a participation of O-2 in gastric mucosal lesion formation, diethyldithiocarbamate (DDC), an inhibitor of Cu,Zn-superoxide dismutase (SOD), was injected into rats and its ulcerogenicity was examined. Subcutaneous injection of DDC was employed, because of high mortality after intraperitoneal injection of the drug. At 7 h after the injection of the drug, many ulcers appeared in the stomach, with suppression of SOD activities in the gastric mucosa, suggesting the participation of O-2 in ulcer formation in the stomach.

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Responses of the ischemic myocardium to allopurinol

Cited by 178 publications

References 15 publications

Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion

Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion

The protective action of allopurinol in an experimental model of haemorrhagic shock and reperfusion

Ulcer Formation in Rat Stomach with Diethyldithiocarbamate

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