Background
Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias
(VAs) by prolonging action potential duration (APD) and facilitating arrhythmogenic
spatially discordant alternans (SDA). Levosimendan, a calcium sensitizer, has been
reported to shorten APD by enhancing the adenosine triphosphate (ATP)-sensitive K
current.
Objective
The purpose of this study was to test the hypothesis that, during TH, levosimendan
shortens the already prolonged APD, attenuates SDA, and prevents VA.
Methods
Langendorff-perfused isolated rabbit hearts were subjected to TH (30°C) for 15 minutes,
followed by treatment with either levosimendan 0.5 μM (n = 9) or vehicle (n = 8) for
an additional 30 minutes under TH. Using an optical mapping system, epicardial APD
was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle
length (PCL) that induces the phenomenon of SDA. Ventricular fibrillation (VF) inducibility
was evaluated by burst pacing for 30 seconds at the shortest PCL that achieved 1:1
ventricular capture.
Results
During TH, levosimendan shortened ventricular APD (PCL 400 ms; from 259 ± 8 ms to
241 ± 18 ms; P = .036) and decreased SDA threshold (from 327 ± 88 ms to 311 ± 68 ms; P = .011). VF inducibility was lowered from 39% ± 30% to 14% ± 12% with levosimendan
(P = .018), whereas APD at PCL 400 ms (P = .161), SDA threshold (P = 1), and VF inducibility (P = .173) were not changed by vehicle.
Conclusion
During TH, levosimendan could protect hearts against VA by shortening APD and decreasing
SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel
approach to preventing VA during TH.
Keywords
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Article info
Publication history
Published online: February 17, 2023
Publication stage
In Press Journal Pre-ProofFootnotes
Funding Sources: This study was supported by grants from the Ministry of Science and Technology (111-2314-B-005-001-MY3), Taiwan; and Taichung Veterans General Hospital (TCVGH-1091004C, TCVGH-PU1098104, TCVGH-AI-10905, TCVGH-1103105C, TCVGH-1103101D, TCVGH-1113102C, TCVGH-1113101D), Taichung, Taiwan. Disclosures: The authors have no conflicts of interest to disclose.
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