Xanthine oxidase as a source of free radical damage in myocardial ischemia

Chambers, David; Parks, Dale A.; Patterson, Guy; Roy, Ranjan; McCord, Joe M.; Yoshida, Shigeo; Parmley, Loren F.; Downey, James M.

doi:10.1016/s0022-2828(85)80017-1

Cited by 636 publications

(178 citation statements)

References 45 publications

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“…16 . For example, myocardial XO enzyme activity was found high in the dog 17 and rat 18 but low in the rabbit 19 and pig. 20 In humans, studies report myocardial XO activity to be either high, 21 low, 22 or undetectable.…”

Section: Discussionmentioning

confidence: 99%

Uric Acid and Survival in Chronic Heart Failure

et al. 2003

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Background-Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). Methods and Results-For the derivation study, 112 patients with CHF (age 59Ϯ12 years, peak oxygen consumption [V O 2 ] 17Ϯ7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (nϭ182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (nϭ120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 mol/L (9.50 mg/dL) (independently of age, peak V O 2 , left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; PϽ0.0001). In the validation study, UA Ն565 mol/L predicted mortality (hazard ratio, 7.14; PϽ0.0001). In 16 patients (from both studies) with UA Ն565 mol/L, left ventricular ejection fraction Յ25% and peak V O 2 Յ14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, PϽ0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. Conclusions-High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.

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Section: Discussionmentioning

confidence: 99%

Uric Acid and Survival in Chronic Heart Failure

et al. 2003

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“…Similarities between our observations and those of other investigators using anoxidreperfused organs suggest that hypoxic/reaerated yeast cultures may be a useful model system to study ischemia-dependent tissue destruction of mammals. Key terms: Yeast, 2',7'-dichlorofluorescein diacetate, propidium iodide, reperfusion injury, dual-parameter analysis Localized ischemia is a major contributing factor to the development of clinical complications associated with various disease processes including myocardial infarction, alcoholic hepatocellular necrosis, and stroke (5,12,16). Tissue hypoxia is also known to extend the damage initiated by trauma-induced lesions (32).…”

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confidence: 99%

Characterization of hypoxia‐dependent peroxide production in cultures of Saccharomyces cerevisiae using flow cytometry: A model for ischemic tissue destruction

Yurkow

McKenzie

1993

Cytometry

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Peroxide production in cultures of Saccharomyces cerevisiae was measured using the H202-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) and flow cytometry. Aeration of cultures of S. cerevisiae exposed to a period of hypoxia was found to induce elevated levels of peroxide that were 100-fold higher than the levels observed in cultures maintained under exclusively aerated or hypoxic conditions. Simultaneous viability analysis, using the fluorescent DNA-intercalating dye propidium iodide, indicated that the increase in peroxide generation preceded cell damage and death. Various agents were found to influence the effect of peroxides on cell viability. The addition of ethanol to hypoxic stationary cultures dramatically increased the rate of cell death without further increasing the amount of peroxide produced, while glucose inhibited peroxide production and decreased the rate of cell death. Surprisingly, elevated peroxide levels of hypoxiclreaerated cultures were maintained upon addition of KH2P0,, although the cells remained viable for extended periods of time when compared to control and other test cultures. Similarities between our observations and those of other investigators using anoxidreperfused organs suggest that hypoxic/reaerated yeast cultures may be a useful model system to study ischemia-dependent tissue destruction of mammals.0 1993 Wiley-Liss, Inc.

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“…(In the previous version, oxygen had positive effects on tissue health, but lack of oxygen was not damaging [22]). A mechanism based on the conversion of xanthine dehydrogenase to xanthine oxidase during ischemia [26,27] was also implemented. The accumulation of xanthine oxidase in ischemic cells represents the potential of a cell to experience reperfusion injury, due to formation of ROS when oxygen reperfuses [26].…”

Section: Work Flowmentioning

confidence: 99%

A computational, tissue-realistic model of pressure ulcer formation in individuals with spinal cord injury

Ziraldo

Solovyev

Allegretti

et al. 2013

Journal of Critical Care

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People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to "better" vs. "worse" outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU. Author SummaryA virtual pressure ulcer was created as a platform to test therapies and determine the mechanisms most correlated with unfavorable outcomes. A layer of tissue fed with oxygen and diffusible molecules via blood vessels could develop an ulcer if pressure was applied, by simulating constriction of blood vessels in a circular region. Simulated ulcers were visually similar to digital photographs of ulcers in individuals with spinal cord injury in their irregular shapes, jagged edges, and overall progression in time. Statistical analyses of simulation outputs revealed that inflammation was an important determinant of ulcer severity and overall tissue damage. However, simulated clinical trials revealed that blocking the negative effects of inflammation could not prevent ulceration, and in order to be beneficial at all for this specific type of ulcer, anti-inflammatory treatments must be applied during the earliest stages of ulcer formation-before many clinical signs of ulceration appear.

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Xanthine oxidase as a source of free radical damage in myocardial ischemia

Cited by 636 publications

References 45 publications

Uric Acid and Survival in Chronic Heart Failure

Uric Acid and Survival in Chronic Heart Failure

Characterization of hypoxia‐dependent peroxide production in cultures of Saccharomyces cerevisiae using flow cytometry: A model for ischemic tissue destruction

A computational, tissue-realistic model of pressure ulcer formation in individuals with spinal cord injury

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