The activity of xanthine oxidase in heart of pigs, guinea pigs, rabbits, rats, and humans

Muxfeldt, Maria; Schäper, Wolfgang

doi:10.1007/bf01907096

Cited by 126 publications

(54 citation statements)

References 28 publications

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“…Since superoxide anion is generated by the Fenton reaction including xanthine oxidase, it is possible that oxygen-free radicals produced during the initial phase of reoxygenation, if any, would cause a deleterious effect on the reoxygenated myocardium. However, in the present study, we perfused rabbit isolated hearts which have been reported to reveal undetectable or negligible xanthine oxidase activity (Ketai et al, 1985;Muxfeldt & Schaper, 1987). In addition, we perfused the heart with Krebs-Henseleit solution without leukocytes which is considered to be one of the sites for freeradical production.…”

Section: Discussionmentioning

confidence: 90%

Beneficial effect of beraprost, a prostacyclin‐mimetic agent, on post‐hypoxic recovery of cardiac function and metabolism in rabbit isolated hearts

Tanonaka¹,

Maruyama²,

Takeo³

1991

British J Pharmacology

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1 The present study was undertaken to determine whether beraprost, a stable prostacyclin-mimetic agent, may exert a beneficial effect on post-hypoxic recovery of cardiac function and metabolism. Isolated rabbit hearts were perfused by the Langendorff method for 20 min under glucose-free hypoxic conditions, followed by 45 min reoxygenation in the presence of glucose, and their functional and metabolic changes with or without beraprost-treatment were examined. 2 Hypoxic insult induced cessation of cardiac contractile force, depletion of myocardial high-energy phosphates, accumulation of tissue calcium, and release of creatine kinase and ATP metabolites. Subsequent reoxygenation resulted in a poor recovery of cardiac contractile force (less than 10% of the pre-hypoxic value), a poor restoration of high-energy phosphates, and increase in calcium content. A further release of creatine kinase and ATP metabolites from the heart was observed during reoxygenation. 3 Treatment with 0.45 pM beraprost during the whole hypoxic period resulted in a significant suppression of the increase in tissue calcium, and the release of creatine kinase and ATP metabolites during hypoxic perfusion. This treatment also elicited a significant post-hypoxic recovery of the cardiac contractile force and the tissue high-energy phosphates. Reoxygenation-induced release of creatine kinase and ATP metabolites was also prevented by treatment with beraprost. 4 When hearts were treated with prostacyclin sodium (0.50uM) in the same manner for the purpose of comparison, similar improvement of post-hypoxic contractile and metabolic recovery were observed. 5 These results demonstrate that treatment with either beraprost or prostacyclin is beneficial for posthypoxic recovery of cardiac function and metabolism. Since the observed effects on post-hypoxic contractile recovery were exerted at a concentration of approximately 0.50pM of these agents (a concentration far from the physiological range) the underlying mechanism appears to be different from the physiological action of prostacyclin.

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Section: Discussionmentioning

confidence: 90%

Beneficial effect of beraprost, a prostacyclin‐mimetic agent, on post‐hypoxic recovery of cardiac function and metabolism in rabbit isolated hearts

Tanonaka¹,

Maruyama²,

Takeo³

1991

British J Pharmacology

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“…A significant source of confusion is the large interspecies variability in tissue expression of XO. 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.…”

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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“…Reports regarding the myocardial content of the enzyme in the human heart are conflicting. [139][140][141][142][143] In contrast to these earlier reports, '147 or filtration,148 by administration of nafazatrom, which inhibits production of leukotrienes,149 by administration of antibodies to the adhesionpromoting Mol glycoprotein,150 and by administration of dextran, which inhibits leukocyte adherence to the endothelium.151 Recent studies have shown that the neutrophil content of the stunned myocardium after a 12-minute period of ischemia is decreased152 and that myeloperoxidase activity (a marker of neutrophils) in myocardium stunned by a 15-minute occlusion is not different from nonischemic myocardium.150 Furthermore, myocardial stun-ning occurs in isolated heart preparations that are devoid of circulating neutrophils. Taken together, these results71'147-'52 suggest that granulocytes do not play a major role in the genesis of postischemic dysfunction after brief, reversible ischemia, although they appear to be major mediators of irreversible tissue injury and vascular obstruction after prolonged periods of ischemia.…”

Section: Decreased Sensitivity Of Myofilaments To Calciummentioning

confidence: 99%

Mechanism of myocardial "stunning".

1990

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Among the numerous mechanisms proposed for myocardial stunning, three appear to be more plausible: 1) generation of oxygen radicals, 2) calcium overload, and 3) excitation-contraction uncoupling. First, the evidence for a pathogenetic role of oxygen-derived free radicals in myocardial stunning is overwhelming. In the setting of a single 15-minute coronary occlusion, mitigation of stunning by antioxidants has been reproducibly observed by several independent laboratories. Similar protection has been recently demonstrated in the conscious animal, that is, in the most physiological experimental preparation available. Furthermore, generation of free radicals in the stunned myocardium has been directly demonstrated by spin trapping techniques, and attenuation of free radical generation has been repeatedly shown to result in attenuation of contractile dysfunction. Numerous observations suggest that oxyradicals also contribute to stunning in other settings: after global ischemia in vitro, after global ischemia during cardioplegic arrest in vivo, and after multiple brief episodes of regional ischemia in vivo. Compelling evidence indicates that the critical free radical damage occurs in the initial moments of reflow, so that myocardial stunning can be viewed as a sublethal form of oxyradical-mediated "reperfusion injury." Second, there is also considerable evidence that a transient calcium overload during early reperfusion contributes to postischemic dysfunction in vitro; however, the importance of this mechanism in vivo remains to be defined. Third, inadequate release of calcium by the sarcoplasmic reticulum, with consequent excitation-contraction uncoupling, may occur after multiple brief episodes of regional ischemia, but its role in other forms of postischemic dysfunction has not been explored. It is probable that multiple mechanisms contribute to the pathogenesis of myocardial stunning. The three hypotheses outlined above are not mutually exclusive and in fact may represent different steps of the same pathophysiological cascade. Thus, generation of oxyradicals may cause sarcoplasmic reticulum dysfunction, and both of these processes may lead to calcium overload, which in turn could exacerbate the damage initiated by oxygen species. The concepts discussed in this review should provide not only a conceptual framework for further investigation of the pathophysiology of reversible ischemia-reperfusion injury but also a rationale for developing clinically applicable interventions designed to prevent postischemic ventricular dysfunction.

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The activity of xanthine oxidase in heart of pigs, guinea pigs, rabbits, rats, and humans

Cited by 126 publications

References 28 publications

Beneficial effect of beraprost, a prostacyclin‐mimetic agent, on post‐hypoxic recovery of cardiac function and metabolism in rabbit isolated hearts

Beneficial effect of beraprost, a prostacyclin‐mimetic agent, on post‐hypoxic recovery of cardiac function and metabolism in rabbit isolated hearts

Uric Acid and Survival in Chronic Heart Failure

Mechanism of myocardial "stunning".

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