Inotropic support is often required to stabilize the hemodynamics of patients with acute decompensated heart failure; while efficacious, it has a history of leading to lethal arrhythmias and/or exacerbating contractile and energetic insufficiencies. Novel therapeutics that can improve contractility independent of beta-adrenergic and protein kinase A-regulated signaling, should be therapeutically beneficial. This study demonstrates that acute protein kinase C-α/β inhibition, with ruboxistaurin at 3 months' post-myocardial infarction, significantly increases contractility and reduces the end-diastolic/end-systolic volumes, documenting beneficial remodeling. These data suggest that ruboxistaurin represents a potential novel therapeutic for heart failure patients, as a moderate inotrope or therapeutic, which leads to beneficial ventricular remodeling.
Keywords: ADHF, acute decompensated heart failure; DIG, digitalis; DOB, dobutamine; ECG, electrocardiogram; EDPVR, end-diastolic pressure-volume relationship; EDV, end-diastolic volume; ESPVR, end-systolic pressure-volume relationship; ESV, end-systolic volume; Ees, elastance end-systole; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; IR, ischemia–reperfusion; LAD, left anterior descending coronary artery; LV, left ventricle/ventricular; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVVPed10, left ventricular end-diastolic volume at a pressure of 10 mm Hg; LVVPes80, left ventricular end- systolic volume at a pressure of 80 mm Hg; MI, myocardial infarction; PKA, protein kinase A; PKC, protein kinase C; PKCα/β inhibitor; PLN, phospholamban; PRSW, pre-load recruitable stroke work; RBX, ruboxistaurin; acute myocardial infarction; heart failure with reduced ejection fraction; invasive hemodynamics; positive inotropy.