Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction
Thomas E. Sharp III, Hajime Kubo, Remus M. Berretta, Timothy Starosta, Markus Wallner, Giana J. Schena, Alexander R. Hobby, Daohai Yu, Danielle M. Trappanese, Jon C. George, Jeffery D. Molkentin and Steven R. Houser
Gross, Cellular, and Molecular Remodeling 3 Months PMI
(A) Gross images of sham heart, whole organ (left), and cross section (right) of mid-myocardium. (B) Gross images of 12-week PMI heart, whole organ (left), and cross section of mid-myocardium (right). (C) Scar size analysis showing viable (white) and scar tissue (black) as a percentage of total myocardial volume at 12 weeks PMI. (D) Bright-field images were taken of Masson’s trichrome–stained mid-myocardial cross sections of the infarct zone (IZ), border zone (BZ), and remote zone (RZ) of a 3 months PMI animal. The 10× (outside images) and 40× (interior images) were acquired to demonstrate fibrosis and the deposition of collagen in the AW and LW of the PMI animal. (E) Heart weight-to-body weight (HW/BW) ratio. (F) Myocyte cross-sectional area calculated from the 2 viable zones (border zone [BZ] and remote zone [RZ]) in sham animals versus 3 months PMI animals. The images represent the BZ in the sham group (F1) and the 3 months PMI group (F2). Large image is 20× and small image (top right corner) is 40×. Data are shown as the mean by anatomic region in the graphs below. (G) Animals underwent sham (n = 6) or MI (n = 6) procedure, and terminal studies were performed at 3 months ± PMI. Tissue was collected for molecular analysis. Protein was isolated and fractionated into cytosolic (C) and membrane (M) fractions. Percentage of membrane-bound fraction over the cytosolic fraction is shown. *p ≤ 0.05; ***p ≤ 0.005 versus sham. Large scale bar = 100 μm. Small scale bar = 50 μm. 3 months PMI = 3-month’s post-myocardial infarction; other abbreviations as in Figure 1.