Mitral Regurgitation Augments Post-Myocardial Infarction RemodelingFailure of Hypertrophic Compensation
Ronen Beeri, MD*,
Chaim Yosefy, MD*,
J. Luis Guerrero, BS*,
Francesca Nesta, MD*,
Suzan Abedat, MSc ,
Miguel Chaput, MD*,
Federica del Monte, MD, PhD ,
Mark D. Handschumacher, BS*,
Robert Stroud, MS||,
Suzanne Sullivan, BS*,
Thea Pugatsch, PhD,
Dan Gilon, MD, FACC,
Gus J. Vlahakes, MD, FACC ,
Francis G. Spinale, MD, FACC||,
Roger J. Hajjar, MD, FACC and
Robert A. Levine, MD, FACC*,*
* Cardiac Ultrasound Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Cardiac Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Heart Institute and Cardiovascular Research Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
|| Cardiothoracic Surgery Department, Medical University of South Carolina, Charleston, South Carolina.
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Figure 2 Schematic and 2D Echocardiographic Image of the LA-LV Shunt Creating MR
Single arrows indicate flow direction; paired arrows indicate shunt exit from the LV. LA = left atrial; MI = myocardial infarction; 2D = 2-dimensional; other abbreviations as in Figure 1.
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Figure 3 Echocardiographic 3D Reconstructions of the Endocardial Surface of the LV
Echocardiographic 3-dimensional (3D) reconstructions of the endocardial surface of infarct (MI) only (A and B) and infarct + MR (C and D) animals at diastole (top) and systole (bottom). Note the enlarged and spherical infarct + MR ventricles. Abbreviations as in Figures 1 and 2.
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Figure 4 Measurement of LV Volumes and Function
End-diastolic volume (EDV) (A) and end-systolic volume (ESV) (B) of infarct-only (yellow bars) and infarct + MR (red bars) sheep at baseline (pre), 1 month follow-up (f/u), and 3 months sacrifice. (C and D) dP/dt and pre-load–recruitable stroke work (PRSW) of infarct-only (broken lines) and infarct + MR (solid lines) sheep at pre, f/u, and 3 months sacrifice. *p < 0.05. Abbreviations as in Figure 1.
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Figure 5 SERCA2a and Phospholamban Quantification
(A) Quantification of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity in remote, border, and infarct regions of experimental and normal control sheep hearts. (B) Immunoblots from different regions of the myocardium in different groups for SERCA2a and phospholamban. Note that in the infarct region, there was residual myocardium that was homogenized and protein extracted. Abbreviations as in Figures 1 and 2.
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Figure 6 Protein Levels of Akt, gp130, and Caspase 3
Protein expression of Akt, gp130, and activated caspase 3 from infarct-only (broken lines) and infarct + mitral regurgitation (solid lines) sheep at baseline, 1 month follow-up (f/u), and 3 months sacrifice. Note the biphasic change in infarct + mitral regurgitation animals for gp130 and Akt expression at follow-up (high) and sacrifice, while no significant change is noted in caspase 3 levels. Values are ± standard error of the mean, *p < 0.01.
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Figure 7 Photomicrographs of Separated Cardiomyocytes
Elongated myocytes from sheep with MI and MR shunt (A) versus more normal cells from MI-only animals (B). Note the different scales used to accommodate the elongated cells of the MI + MR sheep within the field. Abbreviations as in Figures 1 and 2.
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Figure 8 MMP Abundance
Levels of membrane-type (MT) matrix metalloproteinase (MMP)1 and tissue inhibitor of matrix metalloproteinase (TIMP)-4 in the infarct-only ("sham", green bars) and infarct + mitral regurgitation (red bars) animals at first follow-up (T2) and sacrifice (T3) time points. *p < 0.05 relative to baseline; #p < 0.05 for myocardial infarction + mitral regurgitation relative to myocardial infarction only animals for the same zone and stage; $p < 0.05 for sacrifice relative to initial follow-up.
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