Electrical Remolding and Mechanical Changes in Heart Failure: A Model Study

摘要

We have developed a canine cardiac cellular electromechanics model to simulate electrophysiological remodeling of heart failure (HF) and predicted cardiomyocyte contractility after HF. I_(Na L) is integrated into this model to study its role to the prolongation of action potential (AP) in control and HF conditions, which was not established well in the past. It may have a great contribution to prolongation of AP in control and even greater contribution to that of HF. Ionic remolding after HF is modeled by downregulation of I_(tol), I_(K1), I_(Ks), SR pump function and upregulation of Na~+-Ca~(2+) exchange (NCX) and iNa.L-The HF model could successfully simulate the prolonged AP, reduced I_(CaL), enhanced I_(NaCa) and blunted Ca~(2+)transient. With computed Ca~(2+) being the input to myofilament model, myofilament forces are determined. Compared with control, reduced amplitude, increased latency to onset of contraction, increased time to peak (TTP) and attenuated cell shortening are found in HF model. The model could also be embedded into tissue electromechanics model to simulate the altered activation sequence and mechanical function.