Modulation of ventricular fibrillation inducibility and electrical restitution during sympatho-vagal interaction by beta-blocker in isolated rabbit hearts

Abstract

Introduction: Ventricular fibrillation threshold (VFT) and cardiac electrical restitution (RT) are markers of arrhythmia vulnerability, being modulated by sympathetic (SS) and vagus (VS) nerves stimulation. This study aims to assess VFT and RT changes during sympathovagal interaction +/- infusion of metoprolol (BB). Methods: Dual innervated isolated Langendorff perfused rabbit hearts (n=6) were used. VFT was determined as minimum current required to induce sustained VF by burst pacing. Action potential duration and maximum RT slopes were measured by an extrastimulus protocol. The spinal cord was stimulated at the level of stellate ganglia for high frequency SS (11Hz, 9.5V). Right cervical VS was performed at low (LV: 3Hz) and high (HV: 12Hz) frequencies. Protocols were repeated with 1.8muM metoprolol followed by a washout period. Cardiac parameters were measured at steady state. Data are mean+/-SEM, *P<0.05 vs. baseline. Results: At baseline (BL), VS increased VFT in a frequency dependent manner, whilst max RT slope was reduced from 2.3 to 0.9. SS reduced VFT and increased max RT slope (3.9) with concomitant VS having no significant effect on VFT, RT slopes (HS-LV: 2.6; HS-HV: 2.5) and their frequency responses. BB increased overall VFT and reduced max RT slope at BL and during sympathovagal stimulation (Fig. 1). Conclusions: These data suggest that SS retains its effect on VFT and RT over VS during sympathovagal interaction. BB raises overall VFT and abolishes SS dominance over VS, affirming its protective effect and implying possible local noradrenaline release. Further studies on neurotransmitters and ion channel distribution at ventricular level are required. (Figure Presented).