Therapy With Cardiac Contractility Modulation Electrical Signals Improves Left Ventricular Function and Remodeling in Dogs With Chronic Heart Failure
Makoto Imai, MD*,
Sharad Rastogi, MD*,
Ramesh C. Gupta, PhD*,
Sudhish Mishra, PhD*,
Victor G. Sharov, MD, PhD*,
William C. Stanley, PhD ,
Yuval Mika, PhD ,
Benny Rousso, PhD,
Daniel Burkhoff, MD, PhD, FACC,
Shlomo Ben-Haim, MD, PhD and
Hani N. Sabbah, PhD, FACC*,*
* Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio
Impulse Dynamics USA, Inc., Orangeburg, New York.
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Figure 2 Expression of Sarcoplasmic Reticulum Proteins in LV Myocardium
(Left) Western blots of sarcoplasmic reticulum proteins in tissue obtained from the interventricular septum of 2 normal dogs (NL), 2 sham-operated heart failure dogs (Sham), and 2 cardiac contractility modulation (CCM)-treated dogs. (Right) Western blots of the same proteins in tissue obtained from the left ventricular (LV) free wall of the same dogs as in the left panel. CSQ = calsequestrin; PLB = phospholamban; RYR = ryanodine receptor; SERCA-2a = sarcoplasmic reticulum calcium ATPase.
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Figure 3 Protein Expression of PLB in LV Myocardium
(Top) Western blots of PLB in tissue obtained from the interventricular septum of 2 NL, 2 sham-operated heart failure dogs (HF-Sham), and 2 CCM-treated HF dogs (HF + CCM). (Bottom) Western blots of the same protein in tissue obtained from the LV free wall of the same dogs as in the top panel. P-PLB = phosphorylated phospholamban; Ser-16 = serine-16; Thr-17 = threonine-17; Total-PLB = total cardiac phospholamban; other abbreviations as in Figure 2.
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Figure 4 Protein Expression of PLB in LV Myocardium of Dogs Treated With a BB
Western blots of Total-PLB, P-PLB at Ser-16, and P-PLB at Thr-17 in tissue obtained from the LV free wall of 2 NL, 2 control untreated HF dogs (HF-Control), 2 HF dogs treated with beta-blockade only (HF + beta-blocker [BB]), and 2 HF dogs treated with both BB and CCM (HF + BB + CCM). Abbreviations as in Figures 2 and 3.
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Figure 5 Ratio of P-PLB to Total PLB in the LV Anterior Wall
(Top) Bar graph (mean ± SEM) depicting the ratio of P-PLB/Total PLB in LV anterior wall of 6 NL, 6 untreated HF dogs, and 6 CCM-treated HF dogs (HF + CCM). (Bottom) Western blots of P-PLB and Total-PLB in tissue obtained from the LV anterior wall of 2 NL, 2 untreated HF dogs, and 2 CCM-treated HF dogs (HF + CCM). Abbreviations as in Figures 2 and 3.
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Figure 6 Ratio of P-PLB to Total-PLB in the LV Posterior Wall
(Top) Bar graph (mean ± SEM) depicting the ratio of P-PLB/Total-PLB in LV posterior wall of 6 NL, 6 untreated HF dogs, and 6 CCM-treated HF dogs (HF + CCM). (Bottom) Western blots of P-PLB and Total-PLB in tissue obtained from the LV posterior wall of 2 NL, 2 untreated HF dogs, and 2 CCM-treated HF dogs (HF + CCM). Abbreviations as in Figures 2 and 3.
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