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

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Abstract
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 (GD), which is dependent on activation sequence and the spatial dispersion of activation times. GDwas 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 GDthat averaged —-10.8 ± 4.0% (mean ± SD). The rate of change in GDwas 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 GD; mean sensitivity of GDto rote was 0.27 ± 0.12%/beats/min. Intravenous injection of epinephrine produced significant (P < 0.001) decreases in GD 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 GDwere –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 GDto 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. GD 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 GDconstant in the healthy heart during homeostatic disturbance. Applications in closed-loop rate adaptive pacing are described.