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
Serial invasive hemodynamics were performed at baseline (B), 3 months PMI ± DOB, and ± RBX. (A) Representative pressure-volume loops at 3 months after MI + DOB or + RBX. (B) EDPVR was not altered ± DOB, but shifted leftward with RBX. (C) ESPVR was not significantly altered 3 months PMI + DOB but was also shifted leftward with RBX. (D) PRSW was increased at both time points but to a greater extend with RBX. (E) LVVPed10 was significantly reduced in the presence of RBX at 3 months PMI versus 3 months PMI +DOB. (F) The LVVPes80 was significantly reduced at 3 months PMI +RBX, but not ± DOB. (G) EF was increased significantly by DOB and RBX at 3 months PMI, but due to profound reductions in the EDV with RBX. (H) The Ees, 1 of 2 determinants of the ESPVR, was significantly increased at +RBX versus 3 months PMI. (I) The volume intercept, second determinant of the ESPVR, was significantly changed at 3 months PMI + RBX vs. ± DOB. RBX (yellow bars = 2.5 μg/kg/min RBX. *p ≤ 0.05, **p ≤ 0.005 versus baseline; †p ≤ 0.05, ††††p ≤ 0.0005 versus 3 months PMI; ‡p ≤ 0.05, ‡‡‡p ≤ 0.001, ‡‡‡‡p ≤ 0.0005 versus 3 months PMI + DOB. Abbreviations as in Figures 1, 2, and 4.