Effects of tanshinone 6 derivatives on post-hypoxic contractile dysfunction of perfused rat hearts
1994
Yagi, A. (Fukuyama Univ., Hiroshima (Japan). Faculty of Pharmacy and Pharmaceutical Sciences) | Okamura, N. | Tanonaka, K. | Takeo, S.
The present study was undertaken to elucidate the effects of sodium tanshinone 6 1-phenolate, 1'-O-hydrogen succinyltanshinone 6 1-O-hydrogen succinate, and disodium 1'-O-succinyltanshinone 6 1-O-succinate, water-soluble derivatives of tanshinone 6, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of tanshinone 6 as tested previously. The hearts were perfused for 20min under hypoxic conditions, followed by 45min 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 42nM 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 6 derivatives improved posthypoxic 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 6. The results suggest that water-soluble tanshinone 6 derivatives, like tanshinone 6 itself, are beneficial for hypoxia/reoxygenation injury.
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