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

Abstract

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.

Purine metabolism in the heart

“…Similar observations have also been made with dipyridamole [53]. Prevention of adenosine wash-out in the ischaemic-reperfused canine myocardium by mioflazine has also been reported [48].…”

The Effect of Adenosine Transport Inhibition on Cardiovascular Function and Survival after Severe Asphyxia in Fetal Lambs

“…In this way, deamination is inhibited, leading to elevated interstitial Ado levels. This mechanism was demonstrated after pretreatment with the nucleoside transport inhibitor mioflazine (14). Pharmacologic studies on R-7523 1 were even more promising (5).…”