Myocardial viscoelasticity impairs late-filling in working myocardial slice preparations.

Abstract

Heart failure with preserved ejection fraction (HFpEF) is linked to diabetes and obesity and has become the dominant form of heart failure in western cultures. Both impaired relaxation and increased myocardial stiffness impede ventricular filling which manifests in patients as exercise intolerance early in disease progression. The observation of elevated end-diastolic pressure (EDP) in exercising HFpEF patients implies that the passive viscoelasticity of the heart may reduce exercise performance, but no direct experimental methods can assess this ex-vivo. To determine if the passive viscoelastic properties of the myocardium were capable of influencing EDP in exercise, we have developed a myocardial slice-based protocol that permits long-duration mechanical testing with controllable end-diastolic filling velocity. The role of myocardial viscoelasticity on work output is determined by conducting work-loops at varying speeds of end-diastolic filling. Our results demonstrate an increase in the slope of the end diastolic pressure volume relationship (EDPVR) with filling speed in healthy Wistar-Kyoto rats (WKY) suggesting viscoelasticity can limit myocardial filling ex-vivo. To determine if the viscoelastic contribution was predominantly due to myocytes or extracellular matrix (ECM), the passive mechanical properties of the tissue were assessed before and after decellularization. The results indicate that in WKY rats, the ECM contributes minimally to tissue performance under the experimental working conditions. Together, these results suggest that increased myocardial viscoelasticity may contribute to diastolic dysfunction through myocyte stiffening in the absence of overt fibrosis.