Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles

Figures

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  Figure 1. Force Pca Curves Data for multicellular preparations isolated from the left ventricle (LV) and right ventricle (RV) of (A) organ donors and (B) patients who had heart failure. Symbols and table entries show mean ± SEM. Data were acquired as follows: LV organ donor, 9 preparations from 4 hearts; RV organ donor, 12 preparations from 5 hearts; LV heart failure, 22 preparations from 10 hearts; RV heart failure, 24 preparations from 11 hearts. pCa = −log10[Ca2+]. nH = Hill coefficient.

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  Figure 2. Heart Failure Reduces Ca2+-Activated Force in Multicellular Preparations From Both Ventricles (A) Passive (Fpas) and (B) active (Fact) force values deduced by fitting Equation 1 to data from the individual preparations summarized in Figure 1. The total force in pCa 4.5 solution (F) is equal to Fpas+Fact. the mean r2 value for these fits was 0.979 ± 0.002. in this, and all similar Figures, data were analyzed using a linear mixed model that tested for 2 main effects (heart failure status and ventricular region) and their statistical interaction. Post hoc tests were performed using Tukey-Kramer corrections that took into account the number of hearts as well as the number of samples From each heart. Ca2+ = calcium; other abbreviations as in Figure 1.

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  Figure 3. Heart Failure Has a Greater Effect on the Ca2+ Sensitivity of Myocardium From the RV Values of (A) Ca2+sensitivity (pCa50) and (B) cooperativity (nH) deduced by fitting Equation 1 to data from the individual preparations summarized in Figure 1. Abbreviations as in Figure 1.

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  Figure 4. Heart Failure Reduces the Maximum Power Output of Multicellular Preparations From Both Ventricles (A) Representative traces showing (top) force and (bottom) length for a multicellular preparation released to shorten against different loads. (B) Velocity and power plotted against force for these records. (C) Maximum shortening velocity and (D) maximum power for preparations from both ventricles. Data were acquired as follows: LV organ donor, 5 preparations from 3 hearts; RV organ donor, 12 preparations from 5 hearts; LV heart failure, 10 preparations from 7 hearts; RV heart failure, 16 preparations from 8 hearts. Pmax = maximum power output; Vmax = maximum shortening velocity; other abbreviations as in Figure 1.

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  Figure 5. Rates of Tension Recovery Do Not Depend on Heart Failure Status or Ventricular Region at Maximum Levels of Ca2+ Activation (A) Representative traces showing (top) force normalized to cross-sectional area and (bottom) length for a preparation subjected to a rapid shortening/re-stretch protocol (20% muscle length, 20 ms hold). Note the large overshoots that are characteristic of force recovery in human myocardium. The rate of force recovery (ktr) was calculated by fitting a single exponential to the trace between the minimum force after re-stretch and the maximum force attained during the recovery. (B) ktr values plotted against isometric force. Symbols show mean ± SEM for trials in different pCa solutions. Data were acquired from the same preparations summarized in Figure 1. (C) Statistical analysis of ktr values measured in pCa 4.5 solution. Abbreviations as in Figure 1.

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  Figure 6. Heart Failure Modulates the Phosphorylation of Myofilament Proteins (A) Representative images from a gel stained with Pro-Q Diamond (to show phosphorylated proteins) and then SYPRO Ruby (to show total protein). Statistical analyses for (B) troponin I (TnI), (C) myosin binding protein-C (MyBP-C), and (D) regulatory light chain (RLC). Data were acquired as follows: LV organ donor, 8 samples from 4 hearts; RV organ donor, 8 samples from 4 hearts; LV heart failure, 10 samples from 9 hearts; RV heart failure, 8 samples from 8 hearts.

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  Figure 7. Tn1 Phosphorylation Exhibits a Statistical Interaction Between Heart Failure Status and Ventricular Region (A) Western blots probed with antibodies for total TnI (top) and (bottom) TnI phosphorylated at serine 23/24. (B) Data showing phosphorylated TnI to total TnI. Data were acquired as follows: LV organ donor, 4 samples from 4 hearts; RV organ donor, 4 samples from 4 hearts; LV heart failure, 8 samples from 8 hearts; RV heart failure, 8 samples from 8 hearts. Abbreviations as in Figures 1 and 6.