The present study was undertaken to elucidate the effects of
sodium tanshinone VI 1-phenolate (1), 1'-O-hydrogen succinyltanshinone VI 1-O-hydrogen
succinate (2), and
disodium 1'-O-succinyltanshinone VI 1-O-succinate (3), water-soluble derivatives of
tanshinone VI, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of
tanshinone VI as tested previously. The hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation, and their cardiac performance was determined. Changes in tissue
sodium,
potassium,
calcium, and
magnesium contents after reoxygenation, and release of
creatine kinase and
purines and bases (
ATP metabolites) during
hypoxia/reoxygenation were also examined. The derivatives were dissolved in a
Krebs-Henseleit buffer and administered at concentrations of 42 nM into the
buffer.
Hypoxia/reoxygenation resulted in slight recovery of cardiac contractile force, significant alterations in tissue ion concentrations, and pronounced release of
creatine kinase and
ATP metabolites, suggesting
hypoxia/reoxygenation-induced functional and morphological damage. The
tanshinone VI derivatives improved post-hypoxic contractile recovery, which was associated with restoration of tissue ionic concentrations, and diminishment of the release of
creatine kinase and
ATP metabolites from the hypoxic/reoxygenated hearts. The efficacy of these compounds was similar to that of
tanshinone VI. The results suggest that water-soluble
tanshinone VI derivatives, like
tanshinone VI itself, are beneficial for
hypoxia/reoxygenation injury.