The American safety standard for 60 Hz leakage current through the heart was recently increased from 10 muA to 50 muA based on the estimated ability of AC current to induce ventricular fibrillation (VF). VF causes systemic blood pressure collapse, then death. However, we recently showed that pressure collapse can result from leakage currents (84 +/- 27 muA rms) far below those required to induce VF (278 +/- muA in 32 closed-chest humans). The goal of this project is to determine the mechanism by which prolonged, unipolar, microampere, AC stimuli can cause systemic blood pressure collapse without inducing VF. We propose the following hypotheses: (1) Sinusoidal, 60 Hz, unipolar current stimulation lasting three seconds or longer through the in situ heart at rms amplitudes below the VF threshold can consistently elicit a propagated electrical and mechanical response following the same three cellular mechanisms as seen in nerves. (2) As the AC stimulus strength increases the elicited heart rate increases (not rate/rate like pacing) at currents above the stimulation threshold and below the VF threshold, and (3) Once the AC-elicited rate exceeds some threshold, the blood press collapses because the heart becomes isovolumic, developing contractile force either (3.1) synchronously, but without geometric change, or (3.2) asynchronously, leading to ineffective geometry changes. We will show a consistent response in dogs by recording the activation rate of (1A) the elicited electrical response using a new type of notch-filtering electrocardiogram which removes the AC stimulus artifact, and the rate of the mechanical response using (1C) one-dimensional ultrasound and (1B) an epicardial strain gage. The elicited rate for stimulus frequencies from 10-160Hz and ms currents from 10 muA to the VF threshold will be used to determine the relative importance of three cellular-level stimulation mechanisms at 60 Hz. We will (2A) measure the elicited rate as a function of stimulus strength, showing a strength/rate relationship. We will confirm the existence of a rate threshold by showing (3A) that pacing causes pressure collapse at the same rate as AC stimulation. We will demonstrate an isovolumic heart by measuring the volume using (3B) ultrasonic and (3C) impedance techniques. We will (3D) mount multiple strain gages and electrodes on the epicardium, measuring the mechanical and electrical rate and phase to calculate the degree of (3.1) synchrony or (3.2 asynchrony).