Abstract 2434: Contractility Augmentation Induced by Refractory Period Stimulation Depends upon Pacing-Site and Diminishes Over Time
Purpose: Refractory period stimulation (RPS) is proposed as a novel, clinically useful method to improve left (LV) and right ventricular (RV) contractility and might be attributed to local para-vascular sympathetic nerve stimulation. We hypothesize that during RPS contractility is largest during proximal (nerve) stimulation, is related to noradrenaline (NA) release and accompanied by disturbed relaxation.
Methods: RPS was delivered with unipolar, epicardial leads on 3 locations (proximal (p), median (m) and distal (d)) along LAD, LCX, and RCA in open thorax, healthy canines (n=7). RPS consisted of 3 pulses (amplitude 8V, width 1.6 ms) at 40 ms interval, delivered ~40 ms after the R-wave. LV/RV pressures were measured. +dP/dt was used to quantify contractility and −dP/dt used to quantify relaxation. Each site was stimulated for 2 min followed by 5-min baseline. During prolonged RPS-delivery (60 min with 30 min recovery), coronary sinus NA was also measured.
Results: The highest increase in LV+dP/dt was achieved during LADp stimulation (14±7% (mean±sem) increase vs baseline) and lowest during LADd stimulation (9±2%). Delivering RPS along the different LCX locations displayed similar increases in +dP/dt (LCXp; 6%±2%, LCXm; 8±2%, LCXd; 7±2%), but significantly less than the LAD-locations, thus pointing toward a nonuniform sympathetic nerve distribution in the LV wall. RPS at the 3 RCA sites had no effect on LV+dP/dt but greatly enhanced RV+dP/dt (RCAp; 21±6%, RCAm; 22±5%,RCAd; 15±5%, respectively), indicating the localized effect of RPS application. The degree of improvement in LV+dP/dt when using the LAD or LCX was accompanied by similar degree of impairment of LV relaxation (eg for LADp −dP/dt decreased by11±7%). During prolonged RPS delivery, the contractility augmentation significantly decreased from 12±5% to 6±2%. This was accompanied by a similar drop in NA-release into the coronary sinus from 1.08±0.38 to 0.47±0.06 nmol/l (baseline 0.24±0.07 nmol/l).
Conclusion: RPS-induced increase in myocardial contractility depends on the ventricular localization, diminishes over time and most likely involves noradrenalin release from nerve endings. The depression in relaxation is presumably due to regional differences in adrenergic stimulation.