%0 Journal Article %1 Gome_2001_688 %A G�mez, A. M. %A Guatimosim, S. %A Dilly, K. W. %A Vassort, G. %A Lederer, W. J. %D 2001 %J Circulation %K 11489776 Agents, Animals, Calcium Calcium, Cardiotonic Cell Channels, Congestive, Contraction, Failure, Gov't, Heart Hypertrophy, Infarction, Male, Membrane Myocardial Myocardium, Non-U.S. Ouabain, P.H.S., Potentials, Rate, Rats, Research Reticulum, Sarcoplasmic Signaling, Size, Support, Survival Tetrodotoxin, U.S. Wistar, %N 6 %P 688--693 %T Heart failure after myocardial infarction: altered excitation-contraction coupling. %U http://circ.ahajournals.org/cgi/content/full/104/6/688 %V 104 %X BACKGROUND: Heart failure (HF) frequently follows the occurrence of myocardial infarction (MI). Questions about how HF develops and what cellular defects contribute to this dysfunction led to this study. Methods and Results-- MI was induced in rats by coronary artery ligation. Clinical examination of the post-MI (PMI) surviving animals indicated that they were in overt HF by all measures. Cellular examination of the cardiomyocytes by patch-clamp and confocal Ca$^2+$(i) imaging methods indicated that cellular function was significantly compromised. At the single-cell level, Ca$^2+$(i) transient amplitudes were reduced and contractions were decreased and slowed, although Ca$^2+$ current (I(Ca)) remained unchanged. The excitation-contraction coupling (ECC) gain function measured as DeltaCa$^2+$(i)/I(Ca) was significantly decreased. Ouabain, a cardiotonic steroid that blocks the Na$^+$,K$^+$-ATPase and activates Ca$^2+$ entry via cardiac Na$^+$ channels, largely alleviated this defect. CONCLUSIONS: After MI, I(Ca) becomes less able to trigger release of Ca$^2+$ from the sarcoplasmic reticulum. This failure of ECC is a major factor contributing to the development of contractile dysfunction and HF in PMI animals. The improved ECC gain, enhanced Ca$^2+$ entry, and augmented Ca$^2+$ signaling due to cardiotonic steroids contribute to the beneficial effects of these agents.

@article{Gome_2001_688, abstract = {BACKGROUND: Heart failure (HF) frequently follows the occurrence of myocardial infarction ({MI}). Questions about how HF develops and what cellular defects contribute to this dysfunction led to this study. Methods and Results-- {MI} was induced in rats by coronary artery ligation. Clinical examination of the post-{MI} ({PMI}) surviving animals indicated that they were in overt HF by all measures. Cellular examination of the cardiomyocytes by patch-clamp and confocal [{C}a$^{2+}$](i) imaging methods indicated that cellular function was significantly compromised. At the single-cell level, [{C}a$^{2+}$](i) transient amplitudes were reduced and contractions were decreased and slowed, although {C}a$^{2+}$ current (I(Ca)) remained unchanged. The excitation-contraction coupling ({ECC}) gain function measured as Delta[{C}a$^{2+}$](i)/I(Ca) was significantly decreased. Ouabain, a cardiotonic steroid that blocks the {N}a$^{+}$,{K}$^{+}$-ATPase and activates {C}a$^{2+}$ entry via cardiac {N}a$^{+}$ channels, largely alleviated this defect. {CONCLUSIONS}: After {MI}, I(Ca) becomes less able to trigger release of {C}a$^{2+}$ from the sarcoplasmic reticulum. This failure of {ECC} is a major factor contributing to the development of contractile dysfunction and HF in {PMI} animals. The improved {ECC} gain, enhanced {C}a$^{2+}$ entry, and augmented {C}a$^{2+}$ signaling due to cardiotonic steroids contribute to the beneficial effects of these agents.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {G�mez, A. M. and Guatimosim, S. and Dilly, K. W. and Vassort, G. and Lederer, W. J.}, biburl = {https://www.bibsonomy.org/bibtex/217bd38063b3f4fbaccaff8dddb75e487/hake}, description = {The whole bibliography file I use.}, file = {Gome_2001_688.pdf:Gome_2001_688.pdf:PDF}, interhash = {8ed113f4a89a50ad2efd643d84713968}, intrahash = {17bd38063b3f4fbaccaff8dddb75e487}, journal = {Circulation}, keywords = {11489776 Agents, Animals, Calcium Calcium, Cardiotonic Cell Channels, Congestive, Contraction, Failure, Gov't, Heart Hypertrophy, Infarction, Male, Membrane Myocardial Myocardium, Non-U.S. Ouabain, P.H.S., Potentials, Rate, Rats, Research Reticulum, Sarcoplasmic Signaling, Size, Support, Survival Tetrodotoxin, U.S. Wistar,}, month = Aug, number = 6, pages = {688--693}, pmid = {11489776}, timestamp = {2009-06-03T11:21:13.000+0200}, title = {Heart failure after myocardial infarction: altered excitation-contraction coupling.}, url = {http://circ.ahajournals.org/cgi/content/full/104/6/688}, volume = 104, year = 2001 }