Extracellular square wave electric currents applied during the absolute refractory period modulated action potential duration and myocardial contractility in isolated cardiac muscle.
Do square wave electric currents applied during the absolute refractory period modulate contractility in isolated cardiac muscle?
Extracellular currents applied during the absolute refractory period modulate myocardial contractility via sarcoplasmic reticulum-dependent mechanisms, supporting the cellular basis for Cardiac Contractility Modulation in heart failure.
BACKGROUND: Myocardial contractility can be altered using voltage clamp techniques by modulating amplitude and duration of the action potential resulting in enhanced calcium entry in the cell of isolated muscle strips (Non-Excitatory Currents; NEC). Extracellular electrical stimuli delivered during the absolute refractory period (Cardiac Contractility Modulation; CCM) have recently been shown to produce inotropic effects in-vivo. AIM: Understanding the cellular mechanism, underlying the CCM effect, is essential for evaluating its clinical potential. We tested the hypothesis that NEC and CCM modulate contractility via similar cellular mechanisms. METHODS: Square wave electric currents were applied in the organ bath to isometrically contracting rabbit RV papillary muscle and human failing trabecular muscle during the absolute refractory period (ARP). RESULTS: These currents, which did not initiate new action potentials or contractions, modulated action potential duration (shortened or lengthened) and contractility (enhanced or depressed) in a manner that depended upon their amplitude, duration and delay from the pacing stimulus. The contractility modulation effect in the rabbit RV papillary muscle was markedly blunted after exposure to ryanodine, indicating that the sarcoplasmic reticulum plays an important role in the contractility modulation. CONCLUSION: Like voltage clamping, extracellular currents applied during the ARP can similarly modulate action potential duration in-vitro and modulate myocardial contractility by similar intracellular mechanisms. This concept provides the potential of a therapeutic strategy in patients with heart failure to enhance contractility.
Brunckhorst et al. (Tue,) conducted a other in Heart failure. Square wave electric currents during the absolute refractory period (Cardiac Contractility Modulation) was evaluated on Action potential duration and contractility modulation. Extracellular square wave electric currents applied during the absolute refractory period modulated action potential duration and myocardial contractility in isolated cardiac muscle.