Initial alterations of myocardial function and ultrastructure caused by low doses of adriamycin

被引:0
作者
Kapelko, VI [1 ]
Khatkevich, AN [1 ]
Tsyplenkova, VG [1 ]
Beskrovnova, NN [1 ]
机构
[1] Russian Cardiol Sci Ind Complex, Moscow, Russia
关键词
cardiomyopathy; adriamycin; rat; isolated heart;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Adriamycin, an anthracycline antibiotic used for the treartment of tumors, often causes the development of cardiomyopathy. To study initial alterations of myocardial function and ultrastructure, we injected adriamycin to rats in single doses 0,44, 1,31 or 2,19 mg/kg that were similar to therapeutic doses. Even at lowest dose of adriamycin alterations occurred in 5% of cardiomyocytes; myofibrillar alterations appeared as local lysis or contracture, while membrane alterations - as dilation of perinuclear space, sarcoplasmic reticulum and T-system, swelling of mitochondria. At higher doses membrane alterations prevailed. They were observed in 43 and 52% of cells at 1,3 and 2,2 mg/kg, respectively, while myofibrillar alterations were seen only in 15%, of cells. Addition of adriamycin to perfusion solution in concentrations 30 and 50 mu m which were close to two higher doses of adriamycin injected in vivo was associated with decrease of left ventricular developed pressure (by 41 - 44%) and increase of diastolic pressure in the isolated isovolumic heart. The diastolic pressure which in isovolumic mode reflected changes of myocardial diastolic tension was significantly higher in hearts with increased myocardial edema as estimated by the ratio of wet to dry weight of the heart. The results showed a correlation between extent of membrane alterations and negative inotropic effect of adriamycin.
引用
收藏
页码:24 / 29
页数:6
相关论文
共 29 条
  • [1] ACUTE EFFECTS OF DOXORUBICIN ON SKINNED CARDIAC-MUSCLE FIBERS OF GUINEA-PIGS
    ASAYAMA, J
    YAMAHARA, Y
    TATSUMI, T
    MIYAZAKI, H
    INOUE, M
    OMORI, I
    INOUE, D
    NAKAGAWA, M
    [J]. CARDIOVASCULAR RESEARCH, 1992, 26 (04) : 371 - 375
  • [2] HISTOCHEMICAL ALTERATIONS OF ACUTE AND CHRONIC DOXORUBICIN CARDIOTOXICITY
    AVERSANO, RC
    BOOR, PJ
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1983, 15 (08) : 543 - 553
  • [3] FRUCTOSE-1,6-DIPHOSPHATE REDUCES ACUTE ECG-CHANGES DUE TO DOXORUBICIN IN ISOLATED RAT-HEART
    BERNARDINI, N
    DANESI, R
    BERNARDINI, MC
    DELTACCA, M
    [J]. EXPERIENTIA, 1988, 44 (11-12): : 1000 - 1002
  • [4] BILLINGHAM ME, 1978, CANCER TREAT REP, V62, P865
  • [5] Anthracyclines enhance tension development in cardiac muscle by direct interaction with the contractile system
    Bottone, AE
    deBeer, EL
    Voest, EE
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (03) : 1001 - 1008
  • [6] ACUTE EFFECTS OF DOXORUBICIN ON HUMAN LEFT-VENTRICULAR SYSTOLIC AND DIASTOLIC FUNCTION
    BROWN, KA
    BLOW, AJ
    WEISS, RM
    STEWART, JA
    [J]. AMERICAN HEART JOURNAL, 1989, 118 (05) : 979 - 982
  • [7] THE CARDIOTOXIC ANTIBIOTIC DOXORUBICIN INHIBITS THE NA+-CA-2+ EXCHANGE OF DOG HEART SARCOLEMMAL VESICLES
    CARONI, P
    VILLANI, F
    CARAFOLI, E
    [J]. FEBS LETTERS, 1981, 130 (02) : 184 - 186
  • [8] DELTACCA M, 1987, ANTICANCER RES, V7, P703
  • [9] ACUTE EFFECTS OF DOXORUBICIN (ADRIAMYCIN) ON LEFT-VENTRICULAR FUNCTION IN DOGS
    DITCHEY, RV
    LEWINTER, MM
    HIGGINS, CB
    [J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 1984, 6 (03) : 341 - 350
  • [10] FABIATO A, 1982, FED PROC, V41, P2238