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Slow contractions characterize failing rat hearts

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Abstract

The reduced power of the failing heart can be ascribed to a combination of reduced force and slower contraction. We hypothesized that these two properties are due to different cellular mechanisms. We measured contraction parameters both in vivo and in isolated left ventricular (LV) cardiomyocytes from a rat model of post infarction congestive heart failure (CHF). ECG was measured simultaneously with echocardiography and LV pressure, respectively. Shortening and shortening velocity (SV) in isolated cardiomyocytes were measured during different stimulation protocols. LV end diastolic pressure (LVEDP) was 24.6 ± 0.7 mmHg in CHF. LV systolic pressure was decreased by 20%, maximum rate of pressure development in the LV (+dP/dt max) by 36% and time in systole increased by 20% in CHF compared to sham. Electrical remodelling occurred in CHF cells, which were depolarized and had prolonged action potentials (AP) compared to sham cells. Fractional shortening (FS) was increased in CHF compared to sham independent of stimulation protocol. Larger FS was accompanied by increased sarcoplasmic reticulum (SR) Ca2+ load and depended on the electrical remodelling. Time to peak contraction (TTP) was increased in CHF compared to sham cells, but in contrast to FS, TTP was only slightly affected when the cells were stimulated with sham APs and sham diastolic membrane potential (DMP). Contraction duration (corresponding to systolic duration) was 25% longer in CHF than in sham independent on stimulation protocol. We conclude that electrical remodelling affecting DMP and AP duration (APD) significantly affects the size of contraction, whereas the mechanism for slowing of contraction in CHF is different.

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Acknowledgments

We are grateful to Dr. Russell Crawford (University of Dundee, UK) for his generous gift of the Kir6.2 antibody. We would also like to thank Annlaug Ødegaard, Kathrine Andersen, Line Solberg and Fredrik Swift for expert technical assistance, Ståle Nygård for help with the statistics and Tævje StrØmme for preparing the programs in MatLab. Financial support was provided by The National Council of Heart Disease, Ullevaal University Hospital, University of Oslo and Anders Jahre’s Fund for Promotion of Science.

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Correspondence to Janny Bøkenes.

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Returned for 1. Revision: 1 October 2007 1. Revision received: 11 January 2008

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Bøkenes, J., Aronsen, J.M., Birkeland, J.A. et al. Slow contractions characterize failing rat hearts. Basic Res Cardiol 103, 328–344 (2008). https://doi.org/10.1007/s00395-008-0719-y

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