Oral pretreatment with mioflazine completely changes the pattern and remarkably prolongs the accumulation of nucleosides in ischemic and reperfused myocardium.
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.
D000241:Adenosine / Q000032:analysis; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D005260:Female; D007288:Inosine / Q000032:analysis; D008297:Male; D009206:Myocardium / Q000032:analysis*; D009705:Nucleosides / Q000032:analysis*; D009711:Nucleotides / Q000032:analysis; D010710:Phosphates / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D009705:Nucleosides; D009711:Nucleotides; D010710:Phosphates; D010879:Piperazines; D010725:Phosphocreatine; D007288:Inosine; C041518:mioflazine; D000241:Adenosine