Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles

• Published in: Heart rhythm Vol. 5; no. 1; p. 116
• Main Authors: Hayashi, Hideki, Kamanu, Santosh Dora, Ono, Norihiko, Kawase, Ayaka, Chou, Chung-Chuan, Weiss, James N, Karagueuzian, Hrayr S, Lin, Shien-Fong, Chen, Peng-Sheng
• Format: Journal Article
• Language: English
• Published: United States 01.01.2008
• Subjects: Action Potentials; Animals; Calcium - physiology; Electric Stimulation; Electrocardiography; Electrophysiology; Heart Ventricles - innervation; Membrane Potentials; Myocardial Reperfusion; Perfusion; Rabbits; Time Factors; Ventricular Fibrillation - etiology; Ventricular Fibrillation - physiopathology; Ventricular Function; Ventricular Premature Complexes - complications; Ventricular Premature Complexes - physiopathology; Verapamil - pharmacology
• ISSN: 1547-5271
• DOI: 10.1016/j.hrthm.2007.08.020

Single strong premature electrical stimulation (S(2)) may induce figure-eight reentry. We hypothesize that Ca current-mediated slow-response action potentials (APs) play a key role in the propagation in the central common pathway (CCP) of the reentry. We simultaneously mapped optical membrane potential (V(m)) and intracellular Ca (Ca(i)) transients in isolated Langendorff-perfused rabbit ventricles. Baseline pacing (S(1)) and a cathodal S(2) (40-80 mA) were given at different epicardial sites with a coupling interval of 135 +/- 20 ms. In all 6 hearts, S(2) induced graded responses around the S(2) site. These graded responses propagated locally toward the S(1) site and initiated fast APs from recovered tissues. The wavefront then circled around the refractory tissue near the site of S(2). At the side of S(2) opposite to the S(1), the graded responses prolonged AP duration while the Ca(i) continued to decline, resulting in a Ca(i) sinkhole (an area of low Ca(i)). The Ca(i) in the sinkhole then spontaneously increased, followed by a slow V(m) depolarization with a take-off potential of -40 +/- 3.9 mV, which was confirmed with microelectrode recordings in 3 hearts. These slow-response APs then propagated through CCP to complete a figure-eight reentry. We conclude that a strong premature stimulus can induce a Ca(i) sinkhole at the entrance of the CCP. Spontaneous Ca(i) elevation in the Ca(i) sinkhole precedes the V(m) depolarization, leading to Ca current-mediated slow propagation in the CCP. The slow propagation allows more time for tissues at the other side of CCP to recover and be excited to complete figure-eight reentry.