M.Sc Thesis

M.Sc StudentItzhaki Ilanit
SubjectEvaluating the effect of Non Excitatory Stimulation on
cardiac mechanics
DepartmentDepartment of Biomedical Engineering
Supervisor ASSOCIATE PROF. Amir Landesberg


Background: Non-excitatory stimulation (NES) was recently suggested as a new therapeutic modality for severe chronic heart failure. NES is applied during the absolute refractory period of the action potential. It augments cardiac contractility but the underlying mechanisms were not well defined.

Aim: The study tests the role of the sarcoplasmic reticulum (SR) during NES.

Methods: Thin traceculae (n=6) were isolated from rat right ventricles (Krebs-Henseleit solution, 250C, [Ca2+]o=1.5mM). NES was initiated 3msec after the excitation and was 60msec in duration. The sarcomere length was measured by laser diffraction technique. Force was measured by silicon strain gauge. The SR calcium load was assessed by measuring the caffeine (1mM) induced peak isometric force in the presence and absence of NES. SR function was assessed by studying the force frequency relationship (FFR) with and without NES. A model was developed (utilizing Simulink software) to simulate the results.

Results and Discussions: NES gradually increases the peak stress by 36.1±12.3%, with a time constant of 15±0.9sec (0.25Hz stimulation rate). The stress declines gradually after stopping the NES and the stress in the first beat after cessation of NES decreases by only 2.9±0.8% relative to peak stress during NES. NES increases the caffeine induced peak stress by 30.8±7.3%, implying a significant increase in the SR calcium content. NES increases the generated stress at all measured frequencies (15.8±5.9% at 2.50Hz). The FFRs have maxima at an identical frequency with and without NES, insinuating no changes in SR calcium handling.

Conclusions: Analysis of the results stipulates that calcium accumulation within the SR plays a key in modulating cardiac contractility during NES, in the rat.