Cardioprotective effects of mioflazine during 1 h normothermic global ischaemia in the canine heart

Flameng, Willem; Xhonneux, R.; Belle, H. Van; Borgers, M.; Water, A. Van De; Wouters, Luc; Wijnants, J.; Thoné, Fred; Daele, Paul Van; Janßen, Paul

doi:10.1093/cvr/18.9.528

Cited by 44 publications

(16 citation statements)

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“…Eight were pretreated 150 min before LAD occlusion with 2.5 mg. kg 1 orally of mioflazine (R 51 469 -Janssen Pharmaceutica, Beerse, Belgium) and the others served as controls. Further preparation and LAD occlusion was done as described previously (3,15). Control transmural needle biopsies were taken from the non-occluded area, one before ischemia and one at the end of the experiment.…”

Section: Methodsmentioning

confidence: 99%

Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium

Belle

Xhonneux

Flameng³

et al. 1986

Basic Res Cardiol

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In dog myocardium, the changes in the levels of creatine phosphate, inorganic phosphate, ATP, ADP, AMP, adenosine and inosine with 8 min of ischemia and subsequent reperfusion for 2, 4, 8, 16 and 32 min have been followed. Creatine phosphate and inorganic phosphate recovered completely within a few minutes as did the energy charge. However, total nucleotides remained depressed, the decrease being compensated for by the increase in inosine levels during ischemia. There was a rapid removal of the latter with reperfusion. Low oral doses of mioflazine (2.5 mg X kg-1), given 2.5 h before LAD occlusion, did not affect the pattern of changes seen in control animals, except for the nucleosides. The drug induced a complete reversal of the adenosine to inosine ratio during ischemia and a remarkable prolongation of the accumulation within the tissue of mainly adenosine during early reperfusion and inosine afterwards. Assuming that the main action of mioflazine is through inhibition of nucleoside transport, the present results provide interesting information about the mechanism of release, metabolism and final washout of adenosine.

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Section: Methodsmentioning

confidence: 99%

Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium

Belle

Xhonneux

Flameng³

et al. 1986

Basic Res Cardiol

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“…The loss of the sarcolemma's ability to bind Ca 2+ was considered as a first sign of a loss of the cellular Ca 2 ~ -homeostasis because it already occurs during the ischemic phase preceding other signs of membrane degeneration (3,11,16).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural damage and Ca2+-shifts in the canine myocardium subjected to regional incomplete ischemia

et al. 1990

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The role of Ca2+ in the pathogenesis leading to ischemic myocardial cell death is still controversial. To gain insight into this phenomenon a cytochemical procedure, the phosphate pyroantimonate method, was used to localize different subcellular Ca2(+)-pools at the ultrastructural level. After 45 min of left anterior descending coronary artery (LAD) occlusion, the coronary arteries were perfused with triphenyltetrazoliumchloride staining (TTC) to identify viable ischemic and infarcted tissue. In non-ischemic tissue, Ca2(+)-deposits were confined to the sarcolemma, sarcolemma-derived vesicles, transverse tubules, and intercalated disks. In infarcted tissue (TTC-negative), the sarcolemma lost its Ca2(+)-binding capacity and mitochondria were either overloaded with Ca2(+)-precipitate or they contained amorphous densities. In viable ischemic areas (determined with the TTC-technique) the sarcolemma was virtually devoid of Ca2(+)-deposits. Mitochondria in this area frequently showed clumping of the cristae, associated with an accumulation of Ca2(+)-precipitate in between the clustered cristae. The results of this study indicate that Ca2(+)-shifts occur in ischemic myocardial cells before the occurrence of other ultrastructural signs of irreversible injury which, therefore, narrows the possibility that Ca2(+)-overload is only a consequence of ischemic cell death.

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“…Mioflazine, when given orally at 2.5 mg. kg -1 to dogs, markedly protects the heart against one hour of normotherrnic global ischemia (2). As it is a potent nucleoside transport inhibitor, we looked for effects of this compound on the purine pattern in normal heart tissue and in ischemia.…”

Section: A Tissue Levelsmentioning

confidence: 99%

“…Mioflazine, when given orally (2.5 mg. kg -1) to dogs, has a remarkable protective effect against 1 hour of normothermic global ischemia (2). Because this compound is a potent inhibitor of nucleoside transport (Is0 = 4 • 10 -8 M as measured using human erythrocytes), we are interested in the metabolism of nucleotides and nucleosides in the ischemic myocardium.…”

Section: Introductionmentioning

confidence: 99%

Formation and release of nucleosides in the ischemic myocardium. Is the guinea-pig the exception?

1985

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In this study evidence is provided to suggest that nucleoside formation with hypoxia in myocardial tissue from the guinea-pig follows a different course from that in the rat, rabbit or dog. 1) After ischemia, tissue levels of adenosine remain barely detectable in the guinea-pig but rise considerably in the rat and the dog. 2) IMP, remaining almost absent in the dog, does not change in the rat but strongly increases (X 6) in the guinea-pig heart with ischemia. 3) Mioflazine, a nucleoside transport inhibitor, completely reverses the ratio adenosine/inosine in dog myocardium after 8 min of ischemia, making adenosine by far the major nucleoside. No effect could be detected in the guinea-pig. 4) In contrast with the rat and rabbit, ischemia in the guinea-pig does not lead to any considerable release of adenosine upon reperfusion. 5) In the rabbit, the presence of a nucleoside transport inhibitor completely reverses the adenosine/inosine ratio in reperfusates after ischemia. Although the release is strongly inhibited under these conditions in the guinea-pig, adenosine release remains negligible when compared with inosine. 6) Even in the presence of high concentrations of an adenosine deaminase inhibitor, inosine remains the major metabolite released upon reperfusion after ischemia, in the guinea-pig heart.

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Cardioprotective effects of mioflazine during 1 h normothermic global ischaemia in the canine heart

Cited by 44 publications

References 0 publications

Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium

Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium

Ultrastructural damage and Ca2+-shifts in the canine myocardium subjected to regional incomplete ischemia

Formation and release of nucleosides in the ischemic myocardium. Is the guinea-pig the exception?

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