Cardiac contractility modulation by electric currents applied during the refractory period

1 Departments of Medicine and 2 Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032; 3 IMPULSE Dynamics, Tirat Hacarmel, 39120; and 4 Department of Physiology And Biophysics, Technion-Israel Institute of Technology, Haifa 31096, Israel Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude ±20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility ( E es ) from 5.9 ± 2.9 to 8.3 ± 4.6 mmHg/ml with anterior CCM, from 5.3 ± 1.8 to 8.9 ± 4.0 mmHg/ml with posterior CCM, and from 6.1 ± 2.6 to 11.0 ± 7.0 mmHg/ml with combined CCM ( P