Low Intensity Epicardial Pacing During the Absolute Refractory Period Augments Left Ventricular Function Mediated by Local Catecholamine Release.
Biventricular epicardial (Epi) pacing can augment left ventricular (LV) function in heart failure. We postulated that these effects might involve catecholamine release from local autonomic nerve activation. To evaluate this hypothesis we applied low intensity Epi electrical stimuli during the absolute refractory period (ARP), thus avoiding altered activation sequence.



Anesthetized pigs (n = 6) were instrumented with an LV pressure (LVP) transducer, left atrial (LA) and LV Epi pacing electrodes, and sonomicrometer segment length (SL) gauges placed proximal and remote to the LV stimulation site. A catheter was placed into the great cardiac vein adjacent to the LV pacing site for norepinephrine (NE) analysis. During LA pacing at constant rate, 3 pulses (0.8 milliseconds, 2-3x threshold) were applied to the LV Epi electrodes during the ARP. An experimental run consisted of baseline, stimulation (10 minutes), and recovery (5 minutes), repeated 3 times before and after β1 - receptor blockade (BB, metoprolol).



ARP stimulation produced significant increases in cardiac function reflected by elevated LVP, LV, dP/dtmax , and reduced time to LV dP/dtmax . This was accompanied by increased coronary NE levels and increases in LVP versus SL loop area in the remote myocardial segment. In contrast, the proximal segment exhibited early shortening and decreased loop area. BB abolished the changes in SL and LV function despite continued NE release.



These results demonstrate that ARP EPI stimulation induces NE release mediating augmented global LV function. This effect may contribute to the beneficial effect of biventricular Epi pacing in heart failure in some patients.
Donald P. Shiley Bioscience Center, San Diego State University, San Diego, California, USA. brito@mail.sdsu.edu.|University of California, San Diego, California, USA. brito@mail.sdsu.edu.
Bruce R
BR
Ito
University of California, San Diego, California, USA.
James W
JW
Covell
Scripps Clinic and Research, San Diego and La Jolla, California, USA.
Guy P
GP
Curtis
D000200:Action Potentials; D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D006352:Heart Ventricles / Q000187:drug effects / Q000294:innervation*; D023421:Models, Animal; D009200:Myocardial Contraction; D009638:Norepinephrine / Q000378:metabolism*; D010496:Pericardium / Q000294:innervation*; D012032:Refractory Period, Electrophysiological; D034421:Sus scrofa; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure
D058671:Adrenergic beta-1 Receptor Antagonists; D009638:Norepinephrine
absolute refractory period; adrenergic; contractility; norepinephrine; pacing