Persistent Fibrosis and Left Ventricular Chamber Stiffening Despite Cessation of Repetitive Pressure Overload in Swine

To determine whether repetitive pressure overload-induced left ventricular (LV) fibrosis and LV chamber stiffening are reversible upon normalization of hemodynamics, swine were subjected to 2 weeks of daily phenylephrine (2 h/d) followed by a 2-week or 4-week recovery period. Despite cessation of repetitive pressure overload, interstitial fibrosis persisted, and LV chamber stiffness remained increased for up to 4 weeks of recovery. The persistent increase in LV chamber stiffness was accompanied by dynamic changes in extracellular matrix protein expression. The rapid and persistent increase in LV chamber stiffness may explain how hypertrophy-independent LV stiffening develops in the absence of sustained hypertension.