The Ventricular Depolarization Gradient: Effects of Exercise, Pacing Rate, Epinephrine, and Intrinsic Heart Rate Control on the Right Ventricular Evoked Response

A new pacing technique is described that permits high fidelity recording of the paced ventricular evoked response, including cardiac depolarization. Integration of the paced R wave yields the ventricular depolarization gradient (G_D), which is dependent on activation sequence and the spatial dispersion of activation times. G_Dwas studied in 27 dogs to determine the ejects of treadmill exercise at fixed rate pacing (n = 10), elevation of heart rate in the absence of stress (n = 20), epinephrine at fixed rate (n = 6), and exercise in the presence of normal chronotrophic response (n = 7). Low level exercise (1 mph, 2 min, 15°) at a fixed heart rate produced significant (P < 0.0005) decreases in G_Dthat averaged —-10.8 ± 4.0% (mean ± SD). The rate of change in G_Dwas faster at the onset of exercise than at its cessation (P < 0.0005). Artificial elevation of heart rate at rest produced significant (P < 0.0005) increases in G_D; mean sensitivity of G_Dto rote was 0.27 ± 0.12%/beats/min. Intravenous injection of epinephrine produced significant (P < 0.001) decreases in G_D at two dosage levels (2.5 and 5.0 μg/kg) when evaluated at two baseline pacing rates (150 and 190 beats/min); mean changes in G_Dwere –20.64 ± 0.53% (2.5 μ/kg at 150 beats/min), –25.19 ± 4.20% (5.0 μ/kg at 150 beats/min), –14.18 ± 5.19% (2.5 μ/kg at 190 beats/min), and –24.22 ± 4.94% (5.0 μ/kg at 190 beats/min). Sensitivity of G_Dto epinephrine was dose-dependent (P < 0.01) at each baseline rate, but was independent (P > 0.05) of the rate itself. In the presence of a normal chronotropic response. G_D remained unchanged (P > 0.5) during exercise in spite of significant elevation in heart rate (105.0 to 167.1 beats/min, P < 0.001). These data suggest the presence of an intrinsic negative-feedback control mechanism that maintains G_Dconstant in the healthy heart during homeostatic disturbance. Applications in closed-loop rate adaptive pacing are described.