Mechanisms of cardiomyocyte dysfunction in heart failure following myocardial infarction in rats

被引:45
|
作者
Holt, E [1 ]
Tonnessen, T
Lunde, PK
Semb, SO
Wasserstrom, JA
Sejersted, OM
Christensen, G
机构
[1] Ulleval Hosp, Expt Med Res Inst, N-0407 Oslo, Norway
[2] Northwestern Univ, Sch Med, Dept Med Cardiol, Chicago, IL USA
[3] Univ Calif San Diego, Dept Med, Mol Cardiol Program, San Diego, CA 92103 USA
关键词
heart failure; myocytes; calcium; sarcoplasmic reticulum;
D O I
10.1006/jmcc.1998.0724
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Available information regarding the cellular and molecular mechanisms for reduced myocardial function after myocardial infarction (MI) is scarce. In rats with congestive heart failure (CHF), we examined cardiomyocytes isolated from the non-infarcted region of the left ventricle 6 weeks after ligation of the left coronary artery. Systolic left-ventricular pressure was reduced and diastolic pressure was markedly increased in the CHF-rats. The cardiomyocytes isolated from the CHF-hearts had increased resting length, reduced fractional shortening by 31% and a 34% increase in time to 90% relaxation compared to sham cells (P<0.01 for all). Peak L-type calcium currents were not significantly changed, but peak calcium transients measured with fura-2 were reduced by 19% (P<0.01). Moreover, the decline of the calcium transients as measured by the time constant of a monoexponential function was significantly increased by 26% (P<0.01). We also examined the contribution of the Ca2+-ATPase of the sarcoplasmic reticulum (SR) in the removal of cytosolic Ca2+ during relaxation by superfusing cells with 1 mu M thapsigargin that effectively inhibits the Ca2+-ATPase. Relaxation time in CHF-cells was significantly less prolonged when this drug was used (P<0.01). This suggests that other mechanisms, probably the Na+-Ca2+ exchanger, contribute significantly to the relaxation rate in CHF, Simultaneous measurements of fura-2 transients and mechanical shortening did not reveal any alteration in the calcium-myofilament sensitivity in CHF. Our study clearly shows reduced shortening and prolonged relaxation in cardiomyocytes isolated from non-infarcted region of the left ventricle in heart failure. Moreover, we were able to relate the observed cardiomyocyte dysfunction to changes in specific steps in the excitation-contraction coupling. (C) 1998 Academic Press
引用
收藏
页码:1581 / 1593
页数:13
相关论文
共 50 条
  • [41] Elevated plasma protein carbonyls in heart failure and following myocardial infarction
    Winterbourn, C
    Cameron, V
    Mocatta, T
    Pilbrow, A
    Richards, M
    FREE RADICAL BIOLOGY AND MEDICINE, 2005, 39 : S156 - S156
  • [42] Heart Failure Incidence Following ST-Elevation Myocardial Infarction
    Costa, Ricardo
    Trepa, Maria
    Oliveira, Marta
    Frias, Andre
    Campinas, Andreia
    Luz, Andre
    Santos, MArio
    Torres, Severo
    AMERICAN JOURNAL OF CARDIOLOGY, 2022, 164 : 14 - 20
  • [43] A RAT MODEL OF CONGESTIVE HEART FAILURE FOLLOWING MYOCARDIAL INFARCTION.
    Wang, Tong
    Tang, Wanchun
    Sun, Shijie
    Wan, Zhi
    Wang, Hao
    CRITICAL CARE MEDICINE, 2008, 36 (12) : A24 - A24
  • [44] TREATMENT OF ACUTE HEART-FAILURE FOLLOWING MYOCARDIAL-INFARCTION
    NELSON, GIC
    AHUJA, RC
    TAYLOR, SH
    AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE, 1982, 12 (03): : 321 - 322
  • [45] The severity of regional myocardial dysfunction is not affected by cardiomyocyte apoptosis in non-ischemic heart failure
    Prescimone, T.
    Lionetti, V.
    Del Ry, S.
    Caselli, C.
    Cabiati, M.
    Emdin, M.
    Recchia, F.
    Giannessi, D.
    EUROPEAN HEART JOURNAL, 2010, 31 : 423 - 423
  • [46] Severity of regional myocardial dysfunction is not affected by cardiomyocyte apoptosis in non-ischemic heart failure
    Prescimone, Tommaso
    Lionetti, Vincenzo
    Caselli, Chiara
    Aquaro, Giovanni D.
    Cabiati, Manuela
    Ottaviano, Virginia
    Del Ry, Silvia
    Giannessi, Daniela
    PHARMACOLOGICAL RESEARCH, 2011, 63 (03) : 207 - 215
  • [47] Characterizing the Incidence of Heart Failure Following Hospitalizations for Acute Myocardial Infarction
    Nkhoma, Ella
    Ptaszynska, Agata
    Gomez, Andres
    CIRCULATION, 2016, 134
  • [48] Heart failure admissions following ST segment elevation myocardial infarction
    Ezad, Saad
    Al-Omary, Mohammed S.
    Davies, Allan J.
    Leitch, James
    Sverdlov, Aaron L.
    Boyle, Andrew J.
    AUSTRALIAN JOURNAL OF RURAL HEALTH, 2019, 27 (01) : 99 - 100
  • [49] Heart Failure Following Myocardial Infarction: Risk Factors and Trends in Incidence
    Wellings, Jennifer
    Sargsyan, Davit
    Kostis, John B.
    Dobrzynski, Jeanne M.
    Kostis, William J.
    CIRCULATION, 2016, 134
  • [50] Is heart failure the critical warning sign for death following myocardial infarction?
    Moller, Jacob E.
    Torp-Pedersen, Christian
    Kober, Lars V.
    EUROPEAN HEART JOURNAL, 2008, 29 (07) : 833 - 834