Abstract 3151: Stiffness of Hypertrophied Cardiomyocytes Differs in Aortic Stenosis and Arterial Hypertension
Hypertrophied cardiomyocytes(CM) isolated from failing hypertensive hearts with preserved left ventricular(LV) ejection fraction(EF) have a higher resting tension(RT) at fixed sarcomere length than normal CM. This higher RT contributes to the diastolic LV dysfunction observed in these hearts. It is unclear if this higher RT is a specific feature of arterial hypertension(HT)-induced pressure-overload myocardial hypertrophy or if it occurs also in other forms of pressure-overload myocardial hypertrophy such as aortic stenosis(AS). Contractile function was therefore compared in single CM isolated from LV myocardial biopsies of failing hypertensives with preserved LVEF (n=22) and of patients with AS (n=12). All patients were free of coronary artery disease. Isolated CM were briefly submerged in Triton X-100 to remove all membranes and stretched to a sarcomere length of 2.2μm. Maximal total tension(TT) and RT were subsequently measured by incubating CM in activating (i.e. maximal [Ca2+] containing) and relaxing solutions. Myocardial biopsies were also analyzed by histomorphometry for determination of CM diameter and collagen volume fraction (CVF). CM of AS were more hypertrophied than CM of HT as evident from the larger CM diameter (Table⇓). CVF was similar in AS and HT (Table⇓). Despite larger CM diameter, CM of AS had a lower RT/TT ratio than CM of HT (Table⇓). Application of the active subunit of protein kinase A(PKA) lowered RT/TT to similar levels in AS and HT (Table⇓).
Despite less CM hypertrophy in HT, CM of HT are stiffer than CM of AS;
PKA corrects the high stiffness of CM of HT and this suggests a phosphorylatable myofilamentary or cytoskeletal protein to account for the high stiffness;
High CM stiffness appears to be specific for HT-induced myocardial hypertrophy and this specificity could relate to the nature and timing of the pressure-overload, which is resistive and early-systolic in AS and capacitive and late-systolic in HT.