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

Abstract:

OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSIONS: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 putative mechanism of the doxorubicin induced cardiomyopathy, is attributable to the direct effects of doxorubicin on the sarcoplasmic reticulum, impairing its ability to sequester Ca2+.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Asayama J,Yamahara Y,Tatsumi T,Miyazaki H,Inoue M,Omori I,Inoue D,Nakagawa M

doi

10.1093/cvr/26.4.371

subject

Has Abstract

pub_date

1992-04-01 00:00:00

pages

371-5

issue

4

eissn

0008-6363

issn

1755-3245

journal_volume

26

pub_type

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