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.