Apr 1, 1992

Acute effects of doxorubicin on skinned cardiac muscle fibres of guinea pigs

Cardiovascular Research
J AsayamaM Nakagawa

Abstract

The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. Experiments were done on fragments of papillary muscles from the right ventricles of guinea pigs. Skinned fibres were prepared by treatment with saponin. The effects of doxorubicin in concentrations of 2 x 10(-9) to 2 x 10(-5) M on cyclic contractions were evaluated in 20 muscles. The effects of doxorubicin in concentrations of 2 x 10(-7) and 2 x 10(-5) M on pCa-tension relation were examined in 14 muscles treated with Brij-58. Doxorubicin (2 x 10(-9) to 2 x 10(-5) M) increased the frequency of cyclic contractions and induced an incomplete muscle relaxation in a dose dependent manner. Doxorubicin 2 x 10(-7) M had no effect on pCa-tension relation. Doxorubicin 2 x 10(-5) M shifted the pCa-tension curve slightly to the left. An incomplete muscle relaxation is considered to be due to an increase in Ca2+ release from the sarcoplasmic reticulum and a slight increase in the sensitivity of the contractile proteins to Ca2+. These observations suggest that one cause of the intracellular Ca2+ overload induced by doxorubicin, a ...Continue Reading

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Mentioned in this Paper

Doxorubicin
Saponin
Myocardial Contraction
Cyclic Peptides
PIGS
Calcium
Exercise, Isometric
Cavia
Right Ventricular Structure
Protoplasm

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