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 and 3 months PMI. (A) Representative pressure-volume loops from before and 3 months after MI. (B) Both end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure volume relationship (EDPVR) are shown. ESPVR and EDPVR are shifted rightward at 3 months PMI versus baseline. (C) The pre-load recruitable stroke work (PRSW), a load-independent measure. is significantly reduced after MI. (D) LV volume at pressure of 10 mm Hg (LVVPed10) was significantly increased post MI, indicating an increase in capacitance. (E) LVVPes80 was also significantly increased, indicating a reduction in contractility as it pertains to the fore of contraction. (F) Left ventricular ejection fraction was reduced, indicating dilation at 3 months after MI. ***p ≤ 0.001, ****p ≤ 0.0005 versus baseline (B). Abbreviations as in Figure 2.