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
Invasive hemodynamics were performed at baseline ± DOB and 3 months PMI ± DOB. (A) Representative pressure-volume loops in the presence and absence of DOB at baseline and 3 months after MI. (B) EDPVR was not altered at either time point ± DOB. (C) ESPVR was significantly altered (specifically the Ees) at baseline ± DOB, but not at 3 months PMI. (D) PRSW was increased at both time points. (E) LVVPed10 was not significantly reduced in the presences of DOB at 3 months PMI. (F) The LVVPes80 was significantly reduced at baseline ± DOB, but not 3 months PMI ± DOB. (G) EF was increased significantly by DOB at 3 months PMI, but only due to modest reduction in ESV. (H) The Ees, 1 of 2 determinants of the ESPVR, was significantly increased at baseline + DOB, but not at 3 months PMI. (I) The volume intercept, second determinant of the ESPVR, was not significantly changed at 3 months PMI ± DOB. Open bars = baseline (B), and gray bars = dobutamine (+), red bars = 3Mo PMI. *p ≤ 0.05, **p ≤ 0.005, ***p ≤ 0.001, ****p ≤ 0.0005 versus baseline; †p ≤ 0.05 versus 3 months PMI; #p ≤ 0.05, ###p ≤ 0.001, ####p ≤ 0.0005 versus baseline + DOB. NS = nonsignificant; other abbreviations as in Figures 1, 2, and 4.